Nutrient chapter

Riboflavin (vitamin B2)

Vitamin precursor of FMN and FAD.

153 recorded mechanisms · 32 availability situations · 11 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Rat brush-border preparations released free riboflavin from FMN; inhibiting coenzyme hydrolysis reduced its competition with tracer riboflavin uptake.
Flavin mononucleotide → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; intestinal fractionation and EDTA competition experiments
experimental_model
Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings
exposure
Flavin coenzymes with or without EDTA during tracer uptake.
limitations
Rat ex vivo evidence; molecular identities of the hydrolases were not established.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Dietary FMN can supply absorbable riboflavin after intestinal cleavage.
primary_references
[transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263
tissue_or_cell_type
Small-intestinal mucosa
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 111–122
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings · source_derived_draft · unverified_draft
### transport-dietary-fmn-hydrolysis Rat brush-border preparations released free riboflavin from FMN; inhibiting coenzyme hydrolysis reduced its competition with tracer riboflavin uptake. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary FMN can supply absorbable riboflavin after intestinal cleavage. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa experimental_model: Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings limitations: Rat ex vivo evidence; molecular identities of the hydrolases were not established. exposure: Flavin coenzymes with or without EDTA during tracer uptake. evidence_location: Abstract; intestinal fractionation and EDTA competition experiments [transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263
Complete structured claim and evidence
Rat brush-border preparations released free riboflavin from FAD; inhibiting coenzyme hydrolysis reduced its competition with tracer riboflavin uptake.
FAD → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; intestinal fractionation and EDTA competition experiments
experimental_model
Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings
exposure
Flavin coenzymes with or without EDTA during tracer uptake.
limitations
Rat ex vivo evidence; molecular identities of the hydrolases were not established.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Dietary FAD can supply absorbable riboflavin after intestinal cleavage.
primary_references
[transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263
tissue_or_cell_type
Small-intestinal mucosa
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 124–135
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings · source_derived_draft · unverified_draft
### transport-dietary-fad-hydrolysis Rat brush-border preparations released free riboflavin from FAD; inhibiting coenzyme hydrolysis reduced its competition with tracer riboflavin uptake. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary FAD can supply absorbable riboflavin after intestinal cleavage. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa experimental_model: Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings limitations: Rat ex vivo evidence; molecular identities of the hydrolases were not established. exposure: Flavin coenzymes with or without EDTA during tracer uptake. evidence_location: Abstract; intestinal fractionation and EDTA competition experiments [transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263
Complete structured claim and evidence
Expression of human RFVT1 increased cellular riboflavin uptake in HEK293 and Caco-2 experiments.
Riboflavin transporter 1 / SLC52A1 → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Functional characterization of hRFT1
experimental_model
Human transporter expression and radiotracer uptake
exposure
Wild-type transporter expression and radiolabeled riboflavin.
limitations
Expression-system kinetics do not establish whole-body absorption capacity.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFVT1 carries free riboflavin into cells.
primary_references
[transport-rfvt1-2008] Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. (2008). https://doi.org/10.1152/ajpcell.00019.2008 DOI: 10.1152/ajpcell.00019.2008
tissue_or_cell_type
HEK293 and Caco-2 cells
transport_effect
raises Expression increased cellular riboflavin uptake.
transport_pool
the expressing cell Expression increased cellular riboflavin uptake.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 137–148
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression and radiotracer uptake · source_derived_draft · unverified_draft
### transport-rfvt1-influx Expression of human RFVT1 increased cellular riboflavin uptake in HEK293 and Caco-2 experiments. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT1 carries free riboflavin into cells. organism: Homo sapiens tissue_or_cell_type: HEK293 and Caco-2 cells experimental_model: Human transporter expression and radiotracer uptake limitations: Expression-system kinetics do not establish whole-body absorption capacity. exposure: Wild-type transporter expression and radiolabeled riboflavin. evidence_location: Functional characterization of hRFT1 [transport-rfvt1-2008] Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. (2008). https://doi.org/10.1152/ajpcell.00019.2008 DOI: 10.1152/ajpcell.00019.2008
Complete structured claim and evidence
Human RFVT2 expression increased riboflavin uptake in HEK293 cells; uptake did not require extracellular sodium or chloride.
Riboflavin transporter 2 / SLC52A2 → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; comparative HEK293 transport assays
experimental_model
Human RFVT2 expression and radiotracer uptake
exposure
Transient expression; extracellular-ion substitution.
limitations
Older name hRFT3 maps to SLC52A2, not SLC52A3; tissue mRNA enrichment is not transport flux.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFVT2 provides a route for riboflavin entry into cells.
primary_references
[transport-rfvt2-2010] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. (2010). https://doi.org/10.3945/jn.110.122911 DOI: 10.3945/jn.110.122911
tissue_or_cell_type
HEK293 cells
transport_effect
raises Expression increased riboflavin uptake in HEK293 cells.
transport_pool
the expressing cell Expression increased riboflavin uptake in HEK293 cells.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 150–161
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFVT2 expression and radiotracer uptake · source_derived_draft · unverified_draft
### transport-rfvt2-influx Human RFVT2 expression increased riboflavin uptake in HEK293 cells; uptake did not require extracellular sodium or chloride. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT2 provides a route for riboflavin entry into cells. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Human RFVT2 expression and radiotracer uptake limitations: Older name hRFT3 maps to SLC52A2, not SLC52A3; tissue mRNA enrichment is not transport flux. exposure: Transient expression; extracellular-ion substitution. evidence_location: Abstract; comparative HEK293 transport assays [transport-rfvt2-2010] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. (2010). https://doi.org/10.3945/jn.110.122911 DOI: 10.3945/jn.110.122911
Complete structured claim and evidence
Human tissue RT-PCR found strong SLC52A2 mRNA expression in brain and salivary gland.
Riboflavin transporter 2 / SLC52A2 → Brain source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; tissue RT-PCR
experimental_model
Human tissue RT-PCR panel
exposure
No nutrient intervention; tissue-expression survey.
limitations
mRNA abundance neither localizes the protein to a particular neural cell nor quantifies uptake.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFVT2 is expressed in tissues that require access to circulating riboflavin.
primary_references
[transport-rfvt2-2010] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. (2010). https://doi.org/10.3945/jn.110.122911 DOI: 10.3945/jn.110.122911
tissue_or_cell_type
Brain and salivary gland
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 163–174
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human tissue RT-PCR panel · source_derived_draft · unverified_draft
### transport-rfvt2-brain-expression Human tissue RT-PCR found strong SLC52A2 mRNA expression in brain and salivary gland. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT2 is expressed in tissues that require access to circulating riboflavin. organism: Homo sapiens tissue_or_cell_type: Brain and salivary gland experimental_model: Human tissue RT-PCR panel limitations: mRNA abundance neither localizes the protein to a particular neural cell nor quantifies uptake. exposure: No nutrient intervention; tissue-expression survey. evidence_location: Abstract; tissue RT-PCR [transport-rfvt2-2010] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. (2010). https://doi.org/10.3945/jn.110.122911 DOI: 10.3945/jn.110.122911
Complete structured claim and evidence
Tagged human Riboflavin transporter 1 / SLC52A1 localized mainly at the basolateral membrane in polarized Caco-2 and MDCK imaging experiments.
Riboflavin transporter 1 / SLC52A1 → Intestinal epithelial basolateral membrane source_derived_draftungraded
Experimental context and source evidence
evidence_location
Live-cell imaging; historical RFT1/2/3 correspond to RFVT1/3/2
experimental_model
Live-cell confocal imaging of tagged transporter constructs
exposure
Expression of fluorescent transporter constructs.
limitations
Tagged overexpression in epithelial models; not a universal localization map across tissues.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Human proteins in human and canine cells
plain_language
The riboflavin transporters occupy different parts of polarized epithelial cells.
primary_references
[transport-localization-2011] Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21854757/ DOI: 10.1016/j.bbamem.2011.08.004
tissue_or_cell_type
Polarized Caco-2 and MDCK cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 176–187
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Live-cell confocal imaging of tagged transporter constructs · source_derived_draft · unverified_draft
### transport-slc52a1-localization Tagged human Riboflavin transporter 1 / SLC52A1 localized mainly at the basolateral membrane in polarized Caco-2 and MDCK imaging experiments. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The riboflavin transporters occupy different parts of polarized epithelial cells. organism: Human proteins in human and canine cells tissue_or_cell_type: Polarized Caco-2 and MDCK cells experimental_model: Live-cell confocal imaging of tagged transporter constructs limitations: Tagged overexpression in epithelial models; not a universal localization map across tissues. exposure: Expression of fluorescent transporter constructs. evidence_location: Live-cell imaging; historical RFT1/2/3 correspond to RFVT1/3/2 [transport-localization-2011] Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21854757/ DOI: 10.1016/j.bbamem.2011.08.004
Complete structured claim and evidence
Tagged human Riboflavin transporter 2 / SLC52A2 localized mainly in intracellular vesicles, with some basolateral expression in polarized Caco-2 and MDCK imaging experiments.
Riboflavin transporter 2 / SLC52A2 → Intracellular vesicles source_derived_draftungraded
Experimental context and source evidence
evidence_location
Live-cell imaging; historical RFT1/2/3 correspond to RFVT1/3/2
experimental_model
Live-cell confocal imaging of tagged transporter constructs
exposure
Expression of fluorescent transporter constructs.
limitations
Tagged overexpression in epithelial models; not a universal localization map across tissues.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Human proteins in human and canine cells
plain_language
The riboflavin transporters occupy different parts of polarized epithelial cells.
primary_references
[transport-localization-2011] Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21854757/ DOI: 10.1016/j.bbamem.2011.08.004
tissue_or_cell_type
Polarized Caco-2 and MDCK cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 189–200
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Live-cell confocal imaging of tagged transporter constructs · source_derived_draft · unverified_draft
### transport-slc52a2-localization Tagged human Riboflavin transporter 2 / SLC52A2 localized mainly in intracellular vesicles, with some basolateral expression in polarized Caco-2 and MDCK imaging experiments. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The riboflavin transporters occupy different parts of polarized epithelial cells. organism: Human proteins in human and canine cells tissue_or_cell_type: Polarized Caco-2 and MDCK cells experimental_model: Live-cell confocal imaging of tagged transporter constructs limitations: Tagged overexpression in epithelial models; not a universal localization map across tissues. exposure: Expression of fluorescent transporter constructs. evidence_location: Live-cell imaging; historical RFT1/2/3 correspond to RFVT1/3/2 [transport-localization-2011] Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21854757/ DOI: 10.1016/j.bbamem.2011.08.004
Complete structured claim and evidence
Tagged human Riboflavin transporter 3 / SLC52A3 localized at the apical membrane in polarized Caco-2 and MDCK imaging experiments.
Riboflavin transporter 3 / SLC52A3 → Intestinal epithelial apical membrane source_derived_draftungraded
Experimental context and source evidence
evidence_location
Live-cell imaging; historical RFT1/2/3 correspond to RFVT1/3/2
experimental_model
Live-cell confocal imaging of tagged transporter constructs
exposure
Expression of fluorescent transporter constructs.
limitations
Tagged overexpression in epithelial models; not a universal localization map across tissues.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Human proteins in human and canine cells
plain_language
The riboflavin transporters occupy different parts of polarized epithelial cells.
primary_references
[transport-localization-2011] Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21854757/ DOI: 10.1016/j.bbamem.2011.08.004
tissue_or_cell_type
Polarized Caco-2 and MDCK cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 202–213
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Live-cell confocal imaging of tagged transporter constructs · source_derived_draft · unverified_draft
### transport-slc52a3-localization Tagged human Riboflavin transporter 3 / SLC52A3 localized at the apical membrane in polarized Caco-2 and MDCK imaging experiments. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The riboflavin transporters occupy different parts of polarized epithelial cells. organism: Human proteins in human and canine cells tissue_or_cell_type: Polarized Caco-2 and MDCK cells experimental_model: Live-cell confocal imaging of tagged transporter constructs limitations: Tagged overexpression in epithelial models; not a universal localization map across tissues. exposure: Expression of fluorescent transporter constructs. evidence_location: Live-cell imaging; historical RFT1/2/3 correspond to RFVT1/3/2 [transport-localization-2011] Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21854757/ DOI: 10.1016/j.bbamem.2011.08.004
Complete structured claim and evidence
RFVT3-directed siRNA decreased apical radiolabeled-riboflavin uptake by human T84 epithelial cells.
Riboflavin transporter 3 / SLC52A3 → Intestinal riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
RFVT3 siRNA experiment
experimental_model
T84 siRNA and apical tracer-uptake assay
exposure
RFVT3-specific siRNA compared with control siRNA.
limitations
Partial gene silencing in cultured cells; other uptake routes remain possible.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Reducing RFVT3 lowers intestinal-cell riboflavin uptake.
primary_references
[transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013
tissue_or_cell_type
Intestinal epithelial T84 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 215–226
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · T84 siRNA and apical tracer-uptake assay · source_derived_draft · unverified_draft
### transport-rfvt3-silencing RFVT3-directed siRNA decreased apical radiolabeled-riboflavin uptake by human T84 epithelial cells. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing RFVT3 lowers intestinal-cell riboflavin uptake. organism: Homo sapiens tissue_or_cell_type: Intestinal epithelial T84 cells experimental_model: T84 siRNA and apical tracer-uptake assay limitations: Partial gene silencing in cultured cells; other uptake routes remain possible. exposure: RFVT3-specific siRNA compared with control siRNA. evidence_location: RFVT3 siRNA experiment [transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013
Complete structured claim and evidence
RFVT3-expressing HEK293 cells transported riboflavin strongly, FMN weakly, and showed no measurable FAD transport in the reported assay.
Riboflavin transporter 3 / SLC52A3 → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Figure 3C-E
experimental_model
HEK293 expression; HPLC measurement of flavin uptake
exposure
10 micromolar flavin, pH 7.4, 10 minutes, 37 C.
limitations
Substrate preference under these conditions is not proof of zero FMN transport at every concentration.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Free riboflavin was the preferred transported flavin.
primary_references
[transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013
tissue_or_cell_type
HEK293 cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 228–239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 expression; HPLC measurement of flavin uptake · source_derived_draft · unverified_draft
### transport-rfvt3-substrate-discrimination RFVT3-expressing HEK293 cells transported riboflavin strongly, FMN weakly, and showed no measurable FAD transport in the reported assay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free riboflavin was the preferred transported flavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: HEK293 expression; HPLC measurement of flavin uptake limitations: Substrate preference under these conditions is not proof of zero FMN transport at every concentration. exposure: 10 micromolar flavin, pH 7.4, 10 minutes, 37 C. evidence_location: Figure 3C-E [transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013
Complete structured claim and evidence
Lowering extracellular pH from 7.5 to 5.5 increased RFVT3-mediated riboflavin uptake and changed its apparent kinetic parameters.
Riboflavin transporter 3 / SLC52A3 → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Figure 1c-e
experimental_model
Human RFVT3 expression and stable-isotope uptake
exposure
pH 5.5 versus 7.5; concentration-dependent [13C]riboflavin uptake.
limitations
In vitro pH comparison; not advice to alter gastrointestinal acidity.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Acidic conditions enhanced RFVT3 transport in the experiment.
primary_references
[transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7
tissue_or_cell_type
HEK293T cells
transport_effect
raises Lowering extracellular pH increased RFVT3-mediated riboflavin uptake.
transport_pool
the expressing cell Lowering extracellular pH increased RFVT3-mediated riboflavin uptake.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 241–252
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFVT3 expression and stable-isotope uptake · source_derived_draft · unverified_draft
### transport-rfvt3-low-ph Lowering extracellular pH from 7.5 to 5.5 increased RFVT3-mediated riboflavin uptake and changed its apparent kinetic parameters. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acidic conditions enhanced RFVT3 transport in the experiment. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: Human RFVT3 expression and stable-isotope uptake limitations: In vitro pH comparison; not advice to alter gastrointestinal acidity. exposure: pH 5.5 versus 7.5; concentration-dependent [13C]riboflavin uptake. evidence_location: Figure 1c-e [transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7
Complete structured claim and evidence
Purified RFVT3 proteoliposomes showed riboflavin-associated proton influx; D119/E145 mutagenesis identified determinants of pH-sensitive transport.
Riboflavin transporter 3 / SLC52A3 → Cellular riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
evidence_location
Figure 4g-l and discussion
experimental_model
Purified human transporter proteoliposomes and mutagenesis
exposure
Riboflavin addition with proton-sensitive 9-aminoacridine readout.
limitations
Proton/riboflavin stoichiometry and exact residue-specific transport steps remain unresolved.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein in reconstituted membranes
plain_language
RFVT3 can connect riboflavin transport with proton movement.
primary_references
[transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7
tissue_or_cell_type
Cell-free proteoliposomes
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 254–265
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human transporter proteoliposomes and mutagenesis · source_derived_draft · unverified_draft
### transport-rfvt3-proton-coupling Purified RFVT3 proteoliposomes showed riboflavin-associated proton influx; D119/E145 mutagenesis identified determinants of pH-sensitive transport. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT3 can connect riboflavin transport with proton movement. organism: Homo sapiens protein in reconstituted membranes tissue_or_cell_type: Cell-free proteoliposomes experimental_model: Purified human transporter proteoliposomes and mutagenesis limitations: Proton/riboflavin stoichiometry and exact residue-specific transport steps remain unresolved. exposure: Riboflavin addition with proton-sensitive 9-aminoacridine readout. evidence_location: Figure 4g-l and discussion [transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7
Complete structured claim and evidence
Intestine-specific Slc52a3 deletion severely reduced carrier-mediated riboflavin uptake in mouse jejunal/colonic loops and isolated enterocytes.
Intestine-specific Slc52a3-null mouse genotype → Intestinal riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Effect of loss of RFVT-3 on intestinal RF uptake
experimental_model
Conditional knockout with in vivo loops and isolated enterocytes
exposure
Intestinal Slc52a3 deletion versus littermate controls.
limitations
Residual uptake and species differences limit generalization.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Loss of intestinal RFVT3 restricts riboflavin absorption.
primary_references
[transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015
tissue_or_cell_type
Jejunum, colon and isolated intestinal epithelium
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 267–278
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional knockout with in vivo loops and isolated enterocytes · source_derived_draft · unverified_draft
### transport-intestinal-ko-uptake Intestine-specific Slc52a3 deletion severely reduced carrier-mediated riboflavin uptake in mouse jejunal/colonic loops and isolated enterocytes. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of intestinal RFVT3 restricts riboflavin absorption. organism: Mus musculus tissue_or_cell_type: Jejunum, colon and isolated intestinal epithelium experimental_model: Conditional knockout with in vivo loops and isolated enterocytes limitations: Residual uptake and species differences limit generalization. exposure: Intestinal Slc52a3 deletion versus littermate controls. evidence_location: Effect of loss of RFVT-3 on intestinal RF uptake [transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015
Complete structured claim and evidence
Pharmacological riboflavin supplementation corrected growth retardation in the intestinal Slc52a3 conditional-knockout mice.
Riboflavin (vitamin B2) → Mouse postnatal growth source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Effect of RF supplementation on animal phenotype
experimental_model
Riboflavin supplementation in conditional-knockout mice
exposure
Pharmacological riboflavin supplementation as described by the study.
limitations
The rescue does not establish the residual entry route or an effective human dose.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Higher riboflavin exposure rescued growth in this transporter-loss mouse model.
primary_references
[transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015
tissue_or_cell_type
Whole-animal postnatal growth
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 280–291
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin supplementation in conditional-knockout mice · source_derived_draft · unverified_draft
### transport-intestinal-ko-growth-rescue Pharmacological riboflavin supplementation corrected growth retardation in the intestinal Slc52a3 conditional-knockout mice. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher riboflavin exposure rescued growth in this transporter-loss mouse model. organism: Mus musculus tissue_or_cell_type: Whole-animal postnatal growth experimental_model: Riboflavin supplementation in conditional-knockout mice limitations: The rescue does not establish the residual entry route or an effective human dose. exposure: Pharmacological riboflavin supplementation as described by the study. evidence_location: Effect of RF supplementation on animal phenotype [transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015
Complete structured claim and evidence
Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.
Riboflavin kinase / RFK → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract and product-bound structure
experimental_model
Human RFK structural and catalytic mechanism study
exposure
Purified RFK with flavin and adenine nucleotide ligands.
limitations
Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFK performs the first activation step from riboflavin to FMN.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft
### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Human RFK crystallized with MgADP and FMN showed magnesium coordination by an FMN phosphate oxygen and Asn36.
Mg2+ → Riboflavin kinase / RFK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium supports the chemistry used to activate vitamin B2; no blood-magnesium threshold is established.
evidence_location
Abstract; metal-coordination structural analysis
experimental_model
Product-bound human RFK crystallography
exposure
Co-crystallization with MgADP and FMN.
limitations
A metal-bound enzyme structure is not a clinical magnesium-deficiency or supplementation experiment.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Magnesium participates directly in the RFK active site.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 306–318
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-bound human RFK crystallography · source_derived_draft · unverified_draft
### transport-rfk-magnesium-coordination Human RFK crystallized with MgADP and FMN showed magnesium coordination by an FMN phosphate oxygen and Asn36. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium participates directly in the RFK active site. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Product-bound human RFK crystallography limitations: A metal-bound enzyme structure is not a clinical magnesium-deficiency or supplementation experiment. exposure: Co-crystallization with MgADP and FMN. cross_nutrient: Magnesium supports the chemistry used to activate vitamin B2; no blood-magnesium threshold is established. evidence_location: Abstract; metal-coordination structural analysis [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Human FAD synthase isoform 2 adenylylates FMN with ATP to form FAD and pyrophosphate.
Human FAD synthetase isoform 2 → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
evidence_location
FAD synthesis and reverse pyrophosphorolysis assays
experimental_model
Purified recombinant human FADS2 catalytic assays
exposure
ATP and FMN in FAD-synthesis assays.
limitations
Adenylylation is distinct from RFK phosphorylation; reaction products should not be conflated.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
FLAD1 performs the second activation step, making FAD from FMN.
primary_references
[transport-fads2-2011] Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (2011). https://pubmed.ncbi.nlm.nih.gov/21951714/ DOI: 10.1111/j.1742-4658.2011.08368.x
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 320–331
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human FADS2 catalytic assays · source_derived_draft · unverified_draft
### transport-flad1-adenylylation Human FAD synthase isoform 2 adenylylates FMN with ATP to form FAD and pyrophosphate. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLAD1 performs the second activation step, making FAD from FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Purified recombinant human FADS2 catalytic assays limitations: Adenylylation is distinct from RFK phosphorylation; reaction products should not be conflated. exposure: ATP and FMN in FAD-synthesis assays. evidence_location: FAD synthesis and reverse pyrophosphorolysis assays [transport-fads2-2011] Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (2011). https://pubmed.ncbi.nlm.nih.gov/21951714/ DOI: 10.1111/j.1742-4658.2011.08368.x
Complete structured claim and evidence
Purified human FADS2 showed a strict MgCl2 requirement in the reported spectrophotometric FAD-synthesis assay.
Mg2+ → Human FAD synthetase isoform 2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium is a cofactor for a vitamin B2 activation step.
evidence_location
Abstract and activity assay
experimental_model
Recombinant human FADS2 expressed in E. coli and purified
exposure
MgCl2 requirement tested in purified enzyme assays.
limitations
Assay-specific metal dependence does not quantify human dietary magnesium effects on flavins.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein
plain_language
Magnesium supports enzymatic conversion of FMN into FAD.
primary_references
[transport-fads2-2007] Over-expression in Escherichia coli, purification and characterization of isoform 2 of human FAD synthetase. (2007). https://doi.org/10.1016/j.pep.2006.09.002 DOI: 10.1016/j.pep.2006.09.002
tissue_or_cell_type
Purified enzyme
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 333–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human FADS2 expressed in E. coli and purified · source_derived_draft · unverified_draft
### transport-flad1-magnesium-requirement Purified human FADS2 showed a strict MgCl2 requirement in the reported spectrophotometric FAD-synthesis assay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports enzymatic conversion of FMN into FAD. organism: Homo sapiens protein tissue_or_cell_type: Purified enzyme experimental_model: Recombinant human FADS2 expressed in E. coli and purified limitations: Assay-specific metal dependence does not quantify human dietary magnesium effects on flavins. exposure: MgCl2 requirement tested in purified enzyme assays. cross_nutrient: Magnesium is a cofactor for a vitamin B2 activation step. evidence_location: Abstract and activity assay [transport-fads2-2007] Over-expression in Escherichia coli, purification and characterization of isoform 2 of human FAD synthetase. (2007). https://doi.org/10.1016/j.pep.2006.09.002 DOI: 10.1016/j.pep.2006.09.002
Complete structured claim and evidence
In vitro synthesized human FADS1 entered isolated rat liver mitochondria and was processed; transfected-cell imaging also localized it to mitochondria.
Human FAD synthetase isoform 1 → Mitochondria source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; mitochondrial import and confocal imaging
experimental_model
Import into purified rat liver mitochondria; BHK-21/Caco-2 confocal imaging
exposure
In vitro synthesized and transiently expressed human FADS1.
limitations
Construct/import evidence does not establish its abundance in every human tissue.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Human protein; rat mitochondria; hamster and human cells
plain_language
One FLAD1 isoform can provide FAD-synthesis machinery inside mitochondria.
primary_references
[transport-fads-localization-2010] Mitochondrial localization of human FAD synthetase isoform 1. (2010). https://pubmed.ncbi.nlm.nih.gov/20060505/ DOI: 10.1016/j.mito.2009.12.149
tissue_or_cell_type
Liver mitochondria and cultured epithelial cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 347–358
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Import into purified rat liver mitochondria; BHK-21/Caco-2 confocal imaging · source_derived_draft · unverified_draft
### transport-flad1-isoform1-mitochondria In vitro synthesized human FADS1 entered isolated rat liver mitochondria and was processed; transfected-cell imaging also localized it to mitochondria. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One FLAD1 isoform can provide FAD-synthesis machinery inside mitochondria. organism: Human protein; rat mitochondria; hamster and human cells tissue_or_cell_type: Liver mitochondria and cultured epithelial cells experimental_model: Import into purified rat liver mitochondria; BHK-21/Caco-2 confocal imaging limitations: Construct/import evidence does not establish its abundance in every human tissue. exposure: In vitro synthesized and transiently expressed human FADS1. evidence_location: Abstract; mitochondrial import and confocal imaging [transport-fads-localization-2010] Mitochondrial localization of human FAD synthetase isoform 1. (2010). https://pubmed.ncbi.nlm.nih.gov/20060505/ DOI: 10.1016/j.mito.2009.12.149
Complete structured claim and evidence
FADS2 lacked mitochondrial import/localization in the experiments that imported and localized FADS1.
Human FAD synthetase isoform 2 → Cytosol source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; FADS2 comparator
experimental_model
Parallel FADS1/FADS2 import and localization comparison
exposure
In vitro synthesized and transiently expressed human isoforms.
limitations
No import in this assay does not exclude condition-dependent localization outside the tested systems.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Human proteins in mammalian model preparations
plain_language
FLAD1 isoforms differ in access to the mitochondrial compartment.
primary_references
[transport-fads-localization-2010] Mitochondrial localization of human FAD synthetase isoform 1. (2010). https://pubmed.ncbi.nlm.nih.gov/20060505/ DOI: 10.1016/j.mito.2009.12.149
tissue_or_cell_type
Rat liver mitochondria; BHK-21 and Caco-2 cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 360–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Parallel FADS1/FADS2 import and localization comparison · source_derived_draft · unverified_draft
### transport-flad1-isoform2-compartment FADS2 lacked mitochondrial import/localization in the experiments that imported and localized FADS1. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLAD1 isoforms differ in access to the mitochondrial compartment. organism: Human proteins in mammalian model preparations tissue_or_cell_type: Rat liver mitochondria; BHK-21 and Caco-2 cells experimental_model: Parallel FADS1/FADS2 import and localization comparison limitations: No import in this assay does not exclude condition-dependent localization outside the tested systems. exposure: In vitro synthesized and transiently expressed human isoforms. evidence_location: Abstract; FADS2 comparator [transport-fads-localization-2010] Mitochondrial localization of human FAD synthetase isoform 1. (2010). https://pubmed.ncbi.nlm.nih.gov/20060505/ DOI: 10.1016/j.mito.2009.12.149
Complete structured claim and evidence
Purified human FADS2 retained approximately one FAD per enzyme noncovalently; complete release required extensive denaturation.
Human FAD synthetase isoform 2 → FAD source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract; bound-FAD measurements
experimental_model
Purified His-tagged human FADS2 binding and denaturation assays
exposure
Isolated enzyme, chaotrope treatment and denaturation.
limitations
Product retention alone does not prove direct delivery to every cellular flavoprotein.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
FAD can remain tightly associated with the enzyme that makes it.
primary_references
[transport-fads2-2011] Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (2011). https://pubmed.ncbi.nlm.nih.gov/21951714/ DOI: 10.1111/j.1742-4658.2011.08368.x
tissue_or_cell_type
Purified enzyme
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 373–384
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human FADS2 binding and denaturation assays · source_derived_draft · unverified_draft
### transport-flad1-fad-binding Purified human FADS2 retained approximately one FAD per enzyme noncovalently; complete release required extensive denaturation. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FAD can remain tightly associated with the enzyme that makes it. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Purified His-tagged human FADS2 binding and denaturation assays limitations: Product retention alone does not prove direct delivery to every cellular flavoprotein. exposure: Isolated enzyme, chaotrope treatment and denaturation. evidence_location: Abstract; bound-FAD measurements [transport-fads2-2011] Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (2011). https://pubmed.ncbi.nlm.nih.gov/21951714/ DOI: 10.1111/j.1742-4658.2011.08368.x
Complete structured claim and evidence
Recombinant FADS2 carrying p.Ser495del retained less bound flavin than wild-type FADS2.
FLAD1 p.Ser495del variant → FAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 4B
experimental_model
Purified recombinant human FADS2 variant
exposure
Wild-type versus variant purified enzyme.
limitations
Variant numbering follows FADS1; this is not a finding for all FLAD1 variants.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein
plain_language
This FLAD1 variant retains bound FAD less effectively.
primary_references
[transport-flad1-disease-2016] Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4908180/ DOI: 10.1016/j.ajhg.2016.04.006
tissue_or_cell_type
Purified protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 386–397
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human FADS2 variant · source_derived_draft · unverified_draft
### transport-flad1-s495del-binding Recombinant FADS2 carrying p.Ser495del retained less bound flavin than wild-type FADS2. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This FLAD1 variant retains bound FAD less effectively. organism: Homo sapiens protein tissue_or_cell_type: Purified protein experimental_model: Purified recombinant human FADS2 variant limitations: Variant numbering follows FADS1; this is not a finding for all FLAD1 variants. exposure: Wild-type versus variant purified enzyme. evidence_location: Figure 4B [transport-flad1-disease-2016] Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4908180/ DOI: 10.1016/j.ajhg.2016.04.006
Complete structured claim and evidence
Excess FAD reconstitution restored bound flavin and increased proteolytic stability of recombinant p.Ser495del FADS2.
FAD → FLAD1 p.Ser495del variant source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 4A-B
experimental_model
Recombinant variant FAD reconstitution and proteolysis
exposure
Molar excess FAD during in vitro reconstitution.
limitations
Direct FAD exposure in vitro; does not prove universal rescue by dietary riboflavin.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein
plain_language
FAD helped stabilize this particular altered enzyme.
primary_references
[transport-flad1-disease-2016] Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4908180/ DOI: 10.1016/j.ajhg.2016.04.006
tissue_or_cell_type
Purified protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 399–410
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant variant FAD reconstitution and proteolysis · source_derived_draft · unverified_draft
### transport-flad1-s495del-stabilization Excess FAD reconstitution restored bound flavin and increased proteolytic stability of recombinant p.Ser495del FADS2. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FAD helped stabilize this particular altered enzyme. organism: Homo sapiens protein tissue_or_cell_type: Purified protein experimental_model: Recombinant variant FAD reconstitution and proteolysis limitations: Direct FAD exposure in vitro; does not prove universal rescue by dietary riboflavin. exposure: Molar excess FAD during in vitro reconstitution. evidence_location: Figure 4A-B [transport-flad1-disease-2016] Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4908180/ DOI: 10.1016/j.ajhg.2016.04.006
Complete structured claim and evidence
FAD-saturated p.Ser495del and p.Arg530Cys FADS2 remained substantially less catalytically active than wild type.
FAD → FAD synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 5
experimental_model
FAD-saturated purified FADS2 variants
exposure
Molar-excess FAD reconstitution followed by catalytic assays.
limitations
The two variants differ in binding/stability responses; the result concerns maximal in vitro activity.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein
plain_language
Stabilizing a variant does not necessarily restore normal enzyme output.
primary_references
[transport-flad1-disease-2016] Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4908180/ DOI: 10.1016/j.ajhg.2016.04.006
tissue_or_cell_type
Purified protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 412–423
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · FAD-saturated purified FADS2 variants · source_derived_draft · unverified_draft
### transport-flad1-residual-catalytic-defect FAD-saturated p.Ser495del and p.Arg530Cys FADS2 remained substantially less catalytically active than wild type. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stabilizing a variant does not necessarily restore normal enzyme output. organism: Homo sapiens protein tissue_or_cell_type: Purified protein experimental_model: FAD-saturated purified FADS2 variants limitations: The two variants differ in binding/stability responses; the result concerns maximal in vitro activity. exposure: Molar-excess FAD reconstitution followed by catalytic assays. evidence_location: Figure 5 [transport-flad1-disease-2016] Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4908180/ DOI: 10.1016/j.ajhg.2016.04.006
Complete structured claim and evidence
SLC52A2 L123P variant decreased radiolabeled-riboflavin uptake compared with wild-type RFVT2 in transfected HEK293 cells.
SLC52A2 L123P variant → Cellular riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 2a
experimental_model
Transient transporter expression with radiotracer uptake
exposure
10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C.
limitations
Single-variant expression does not reproduce all neural tissue effects.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The disease-associated transporter variant imports less riboflavin.
primary_references
[transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y
tissue_or_cell_type
HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 425–436
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient transporter expression with radiotracer uptake · source_derived_draft · unverified_draft
### transport-slc52a2-l123p-uptake SLC52A2 L123P variant decreased radiolabeled-riboflavin uptake compared with wild-type RFVT2 in transfected HEK293 cells. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The disease-associated transporter variant imports less riboflavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Transient transporter expression with radiotracer uptake limitations: Single-variant expression does not reproduce all neural tissue effects. exposure: 10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C. evidence_location: Figure 2a [transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y
Complete structured claim and evidence
SLC52A2 L339P variant decreased radiolabeled-riboflavin uptake compared with wild-type RFVT2 in transfected HEK293 cells.
SLC52A2 L339P variant → Cellular riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 2a
experimental_model
Transient transporter expression with radiotracer uptake
exposure
10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C.
limitations
Single-variant expression does not reproduce all neural tissue effects.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The disease-associated transporter variant imports less riboflavin.
primary_references
[transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y
tissue_or_cell_type
HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 438–449
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient transporter expression with radiotracer uptake · source_derived_draft · unverified_draft
### transport-slc52a2-l339p-uptake SLC52A2 L339P variant decreased radiolabeled-riboflavin uptake compared with wild-type RFVT2 in transfected HEK293 cells. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The disease-associated transporter variant imports less riboflavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Transient transporter expression with radiotracer uptake limitations: Single-variant expression does not reproduce all neural tissue effects. exposure: 10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C. evidence_location: Figure 2a [transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y
Complete structured claim and evidence
The child with compound SLC52A2 L123P/L339P variants had normal measured plasma riboflavin, FMN and FAD despite a transport-associated neurologic disorder.
Riboflavin transporter 2 / SLC52A2 → Plasma riboflavin, FMN and FAD concentrations source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Table 3 and Methods/results
experimental_model
Single genetic case; plasma flavin assay
exposure
Pretreatment plasma measurements.
limitations
One case; normal plasma measurements are not direct measurements of neuronal flavin sufficiency.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Normal plasma flavins did not exclude a cellular transport defect.
primary_references
[transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y
tissue_or_cell_type
Plasma and clinical nervous-system phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 451–462
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single genetic case; plasma flavin assay · source_derived_draft · unverified_draft
### transport-slc52a2-normal-plasma The child with compound SLC52A2 L123P/L339P variants had normal measured plasma riboflavin, FMN and FAD despite a transport-associated neurologic disorder. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Normal plasma flavins did not exclude a cellular transport defect. organism: Homo sapiens tissue_or_cell_type: Plasma and clinical nervous-system phenotype experimental_model: Single genetic case; plasma flavin assay limitations: One case; normal plasma measurements are not direct measurements of neuronal flavin sufficiency. exposure: Pretreatment plasma measurements. evidence_location: Table 3 and Methods/results [transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y
Complete structured claim and evidence
RFVT2 W31S abolished measurable uptake despite detectable membrane expression in the study, separating transport failure from simple protein absence.
SLC52A2 W31S variant → Cellular riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 5A-B
experimental_model
HEK293 transient expression, tracer uptake and membrane immunoblot
exposure
W31S expression compared with wild type.
limitations
Crude-membrane detection does not quantify correctly oriented surface protein.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A transporter can reach the membrane yet fail to carry riboflavin.
primary_references
[transport-slc52a2-neuronopathy-2014] Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2 (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3891447/ DOI: 10.1093/brain/awt315
tissue_or_cell_type
HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 464–475
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 transient expression, tracer uptake and membrane immunoblot · source_derived_draft · unverified_draft
### transport-slc52a2-w31s-intrinsic-defect RFVT2 W31S abolished measurable uptake despite detectable membrane expression in the study, separating transport failure from simple protein absence. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can reach the membrane yet fail to carry riboflavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: HEK293 transient expression, tracer uptake and membrane immunoblot limitations: Crude-membrane detection does not quantify correctly oriented surface protein. exposure: W31S expression compared with wild type. evidence_location: Figure 5A-B [transport-slc52a2-neuronopathy-2014] Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2 (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3891447/ DOI: 10.1093/brain/awt315
Complete structured claim and evidence
SLC52A1 c.1134+11G>A created a binding site for splice-inhibitory hnRNP A1 and promoted exon 4 skipping.
SLC52A1 c.1134+11G>A variant → SLC52A1 exon 4 skipping source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Abstract; variant splicing mechanism
experimental_model
Variant functional splicing studies accompanying a clinical case
exposure
Variant versus reference SLC52A1 splicing context.
limitations
Clinical severity may depend on maternal nutritional context; mechanism should not be generalized to all intronic variants.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
An intronic change can disrupt production of the riboflavin transporter.
primary_references
[transport-slc52a1-splicing-2017] An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/29122468/ DOI: 10.1016/j.ymgme.2017.10.014
tissue_or_cell_type
Human SLC52A1 transcript in functional assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 477–488
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Variant functional splicing studies accompanying a clinical case · source_derived_draft · unverified_draft
### transport-slc52a1-splice-silencer SLC52A1 c.1134+11G>A created a binding site for splice-inhibitory hnRNP A1 and promoted exon 4 skipping. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intronic change can disrupt production of the riboflavin transporter. organism: Homo sapiens tissue_or_cell_type: Human SLC52A1 transcript in functional assays experimental_model: Variant functional splicing studies accompanying a clinical case limitations: Clinical severity may depend on maternal nutritional context; mechanism should not be generalized to all intronic variants. exposure: Variant versus reference SLC52A1 splicing context. evidence_location: Abstract; variant splicing mechanism [transport-slc52a1-splicing-2017] An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/29122468/ DOI: 10.1016/j.ymgme.2017.10.014
Complete structured claim and evidence
K235R/K235R and Y174C/K235R mouse muscle mitochondria accumulated less isotope-labeled FAD; Slc25a32-null embryonic mitochondria also had impaired FAD uptake.
Slc25a32 K235R-containing mouse genotypes → Mitochondrial FAD uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 5C-D
experimental_model
Stable-isotope uptake in isolated knock-in/knockout mitochondria
exposure
10 micromolar isotope-labeled FAD; knockout embryo endpoint at 60 minutes.
limitations
Organelle uptake supports carrier dependence but does not establish exchange partner or transport stoichiometry.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
The carrier defect restricts access to mitochondrial FAD.
primary_references
[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Skeletal muscle and embryonic mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 490–501
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope uptake in isolated knock-in/knockout mitochondria · source_derived_draft · unverified_draft
### transport-slc25a32-fad-import K235R/K235R and Y174C/K235R mouse muscle mitochondria accumulated less isotope-labeled FAD; Slc25a32-null embryonic mitochondria also had impaired FAD uptake. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier defect restricts access to mitochondrial FAD. organism: Mus musculus tissue_or_cell_type: Skeletal muscle and embryonic mitochondria experimental_model: Stable-isotope uptake in isolated knock-in/knockout mitochondria limitations: Organelle uptake supports carrier dependence but does not establish exchange partner or transport stoichiometry. exposure: 10 micromolar isotope-labeled FAD; knockout embryo endpoint at 60 minutes. evidence_location: Figure 5C-D [transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
The tested Slc25a32 mutant muscle mitochondria did not show impaired uptake of isotope-labeled free riboflavin.
Slc25a32 K235R-containing mouse genotypes → Mitochondrial riboflavin uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 5C
experimental_model
Stable-isotope riboflavin uptake in isolated muscle mitochondria
exposure
10 micromolar labeled riboflavin.
limitations
The identity of the preserved riboflavin-entry route was not established.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
A mitochondrial FAD transport defect need not be a free-riboflavin import defect.
primary_references
[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Skeletal-muscle mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 503–514
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope riboflavin uptake in isolated muscle mitochondria · source_derived_draft · unverified_draft
### transport-slc25a32-riboflavin-selectivity The tested Slc25a32 mutant muscle mitochondria did not show impaired uptake of isotope-labeled free riboflavin. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mitochondrial FAD transport defect need not be a free-riboflavin import defect. organism: Mus musculus tissue_or_cell_type: Skeletal-muscle mitochondria experimental_model: Stable-isotope riboflavin uptake in isolated muscle mitochondria limitations: The identity of the preserved riboflavin-entry route was not established. exposure: 10 micromolar labeled riboflavin. evidence_location: Figure 5C [transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Slc25a32 mutant and knockout mitochondrial preparations retained folate-substrate uptake in the 2022 mouse study.
Mouse Slc25a32 mitochondrial carrier → Mitochondrial folate uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Separates primary flavin import from secondary folate-pool changes.
evidence_location
Abstract and folate-uptake experiments
experimental_model
Folate uptake in genetically altered isolated mitochondria
exposure
Labeled folic acid or 5-formyltetrahydrofolate in mitochondrial uptake assays.
limitations
Preserved uptake in this model does not fully resolve older human-cDNA complementation results.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved.
primary_references
[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Muscle and embryonic mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 516–528
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Folate uptake in genetically altered isolated mitochondria · source_derived_draft · unverified_draft
### transport-slc25a32-folate-uptake-preserved Slc25a32 mutant and knockout mitochondrial preparations retained folate-substrate uptake in the 2022 mouse study. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mouse experiments attributed the primary import defect to FAD, with folate uptake preserved. organism: Mus musculus tissue_or_cell_type: Muscle and embryonic mitochondria experimental_model: Folate uptake in genetically altered isolated mitochondria limitations: Preserved uptake in this model does not fully resolve older human-cDNA complementation results. exposure: Labeled folic acid or 5-formyltetrahydrofolate in mitochondrial uptake assays. cross_nutrient: Separates primary flavin import from secondary folate-pool changes. evidence_location: Abstract and folate-uptake experiments [transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Human SLC25A32 cDNA restored mitochondrial folate accumulation and complemented glycine auxotrophy in CHO glyB cells, supporting the original folate-carrier interpretation.
SLC25A32 mitochondrial carrier → Mitochondrial folate accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Historical vitamin B9 interpretation of a carrier now implicated in vitamin B2 cofactor supply.
evidence_location
Abstract; complementation and mitochondrial folate accumulation
experimental_model
Human placental cDNA complementation of CHO glyB cells
exposure
Retroviral human cDNA and subcloned cDNA expression.
limitations
Steady-state accumulation and growth rescue do not distinguish direct folate transport from indirect metabolic rescue.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Human cDNA in Cricetulus griseus cells
plain_language
Early rescue experiments linked this carrier to mitochondrial folate availability.
primary_references
[transport-slc25a32-2000] Retrovirally mediated complementation of the glyB phenotype. Cloning of a human gene encoding the carrier for entry of folates into mitochondria. (2000). https://pubmed.ncbi.nlm.nih.gov/10978331/ DOI: 10.1074/jbc.M005163200
tissue_or_cell_type
Cultured CHO glyB cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 530–542
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human placental cDNA complementation of CHO glyB cells · source_derived_draft · unverified_draft
### transport-slc25a32-historical-folate-rescue Human SLC25A32 cDNA restored mitochondrial folate accumulation and complemented glycine auxotrophy in CHO glyB cells, supporting the original folate-carrier interpretation. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Early rescue experiments linked this carrier to mitochondrial folate availability. organism: Human cDNA in Cricetulus griseus cells tissue_or_cell_type: Cultured CHO glyB cells experimental_model: Human placental cDNA complementation of CHO glyB cells limitations: Steady-state accumulation and growth rescue do not distinguish direct folate transport from indirect metabolic rescue. exposure: Retroviral human cDNA and subcloned cDNA expression. cross_nutrient: Historical vitamin B9 interpretation of a carrier now implicated in vitamin B2 cofactor supply. evidence_location: Abstract; complementation and mitochondrial folate accumulation [transport-slc25a32-2000] Retrovirally mediated complementation of the glyB phenotype. Cloning of a human gene encoding the carrier for entry of folates into mitochondria. (2000). https://pubmed.ncbi.nlm.nih.gov/10978331/ DOI: 10.1074/jbc.M005163200
Complete structured claim and evidence
Abcg2-null dams had approximately 63-fold lower free riboflavin in milk than wild type on standard chow.
Abcg2-null mouse genotype → Riboflavin secretion into milk source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 5A
experimental_model
Lactating knockout/wild-type mouse comparison with HPLC
exposure
Chow containing 12-14 mg/kg riboflavin; lactating dams.
limitations
Mouse result; magnitude depends on chow and lactation conditions.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
ABCG2 normally makes a major contribution to riboflavin delivery into milk.
primary_references
[transport-abcg2-2007] Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC1800714/ DOI: 10.1128/MCB.01621-06
tissue_or_cell_type
Mammary milk
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 544–555
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lactating knockout/wild-type mouse comparison with HPLC · source_derived_draft · unverified_draft
### transport-abcg2-milk-riboflavin Abcg2-null dams had approximately 63-fold lower free riboflavin in milk than wild type on standard chow. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ABCG2 normally makes a major contribution to riboflavin delivery into milk. organism: Mus musculus tissue_or_cell_type: Mammary milk experimental_model: Lactating knockout/wild-type mouse comparison with HPLC limitations: Mouse result; magnitude depends on chow and lactation conditions. exposure: Chow containing 12-14 mg/kg riboflavin; lactating dams. evidence_location: Figure 5A [transport-abcg2-2007] Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC1800714/ DOI: 10.1128/MCB.01621-06
Complete structured claim and evidence
Milk FAD concentrations were unchanged in Abcg2-null dams, demonstrating an ABCG2-independent route for milk vitamin B2 equivalents.
Abcg2-null mouse genotype → FAD secretion into milk source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 5A and discussion
experimental_model
Lactating knockout/wild-type mouse comparison with HPLC
exposure
Standard-chow lactating knockout and wild-type mice.
limitations
The independent FAD secretion machinery was not identified.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Milk retains another flavin supply route when free-riboflavin secretion falls.
primary_references
[transport-abcg2-2007] Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC1800714/ DOI: 10.1128/MCB.01621-06
tissue_or_cell_type
Mammary milk
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 557–568
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lactating knockout/wild-type mouse comparison with HPLC · source_derived_draft · unverified_draft
### transport-abcg2-independent-milk-fad Milk FAD concentrations were unchanged in Abcg2-null dams, demonstrating an ABCG2-independent route for milk vitamin B2 equivalents. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Milk retains another flavin supply route when free-riboflavin secretion falls. organism: Mus musculus tissue_or_cell_type: Mammary milk experimental_model: Lactating knockout/wild-type mouse comparison with HPLC limitations: The independent FAD secretion machinery was not identified. exposure: Standard-chow lactating knockout and wild-type mice. evidence_location: Figure 5A and discussion [transport-abcg2-2007] Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC1800714/ DOI: 10.1128/MCB.01621-06
Complete structured claim and evidence
FMN restored rotenone-sensitive NADH:quinone reductase activity after alkaline reductive inactivation of bovine membrane-bound complex I.
Flavin mononucleotide → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}]
experimental_model
Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.
exposure
10 micromolar FMN after NADH/respiratory blockade at pH 10.
limitations
pH 10 treatment; not a test of dietary deficiency or oral supplementation.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Bos taurus
plain_language
Putting the correct flavin back restored this experimentally inactivated respiratory enzyme.
primary_references
[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
tissue_or_cell_type
Heart submitochondrial particles
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 570–581
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft
### b2-met-complex-i-fmn-reconstitution FMN restored rotenone-sensitive NADH:quinone reductase activity after alkaline reductive inactivation of bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Putting the correct flavin back restored this experimentally inactivated respiratory enzyme. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: pH 10 treatment; not a test of dietary deficiency or oral supplementation. exposure: 10 micromolar FMN after NADH/respiratory blockade at pH 10. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
Complete structured claim and evidence
NADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I.
NADH → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}]
experimental_model
Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.
exposure
NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays.
limitations
Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Bos taurus
plain_language
An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.
primary_references
[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
tissue_or_cell_type
Heart submitochondrial particles
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 583–594
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft
### b2-met-complex-i-reductive-fmn-loss NADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH. exposure: NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
Complete structured claim and evidence
Riboflavin and FAD failed to protect or reactivate alkaline-inactivated bovine complex I under conditions where FMN did.
Riboflavin (vitamin B2) → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}]
experimental_model
Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.
exposure
10 micromolar riboflavin, FAD or FMN in the reconstitution comparison.
limitations
Does not test intact-cell conversion of riboflavin into FMN.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Bos taurus
plain_language
Free B2 and FAD could not substitute directly for FMN in this test tube.
primary_references
[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
tissue_or_cell_type
Heart submitochondrial particles
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 596–607
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft
### b2-met-complex-i-flavin-specificity Riboflavin and FAD failed to protect or reactivate alkaline-inactivated bovine complex I under conditions where FMN did. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free B2 and FAD could not substitute directly for FMN in this test tube. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: Does not test intact-cell conversion of riboflavin into FMN. exposure: 10 micromolar riboflavin, FAD or FMN in the reconstitution comparison. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048
Complete structured claim and evidence
Riboflavin-free culture reduced complex I abundance; human 143B proteomics identified particularly strong loss of its NADH-oxidizing N-module subunits.
Riboflavin (vitamin B2) → Mitochondrial respiratory complex I source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]
experimental_model
Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.
exposure
Riboflavin-free medium; matched control contained 1 micromolar riboflavin.
limitations
Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens; Mus musculus
plain_language
Removing B2 reduced parts needed to build the respiratory enzyme.
primary_references
[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
tissue_or_cell_type
143B cells and mouse adult fibroblasts
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 609–620
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft
### b2-met-depletion-complex-i Riboflavin-free culture reduced complex I abundance; human 143B proteomics identified particularly strong loss of its NADH-oxidizing N-module subunits. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing B2 reduced parts needed to build the respiratory enzyme. organism: Homo sapiens; Mus musculus tissue_or_cell_type: 143B cells and mouse adult fibroblasts experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold. exposure: Riboflavin-free medium; matched control contained 1 micromolar riboflavin. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
Complete structured claim and evidence
DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline.
Riboflavin (vitamin B2) → DLD source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]
experimental_model
Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.
exposure
Riboflavin-free medium compared with matched replete medium.
limitations
No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.
primary_references
[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
tissue_or_cell_type
143B cell proteomics
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–634
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft
### b2-met-depletion-dld DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme. organism: Homo sapiens tissue_or_cell_type: 143B cell proteomics experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins. exposure: Riboflavin-free medium compared with matched replete medium. cross_nutrient: Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
Complete structured claim and evidence
Cryo-EM of active human complex II resolved FAD within SDHA and located the succinate-fumarate active site between its FAD-binding and capping domains.
SDHA → FAD source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 3, "char_start": 0, "char_end": 2164, "evidence_access": "full-text"}]
experimental_model
Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Structure establishes location, not nutritional sensitivity.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The B2-derived cofactor sits in the catalytic SDHA part of complex II.
primary_references
[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
tissue_or_cell_type
HEK293F-derived purified complex II
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 636–647
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft
### b2-met-human-sdha-fad Cryo-EM of active human complex II resolved FAD within SDHA and located the succinate-fumarate active site between its FAD-binding and capping domains. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B2-derived cofactor sits in the catalytic SDHA part of complex II. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structure establishes location, not nutritional sensitivity. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 3, "char_start": 0, "char_end": 2164, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
Complete structured claim and evidence
Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system.
Human succinate dehydrogenase iron-sulfur subunit / SDHB → [4Fe-4S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]
experimental_model
Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Complex II couples a B2-derived flavin with separate iron-sulfur centers.
primary_references
[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
tissue_or_cell_type
HEK293F-derived purified complex II
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 649–661
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft
### b2-met-human-sdhb-iron-sulfur Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Complex II couples a B2-derived flavin with separate iron-sulfur centers. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
Complete structured claim and evidence
Purified human complex II coupled succinate oxidation to ubiquinone reduction in a UQ1/DCIP assay, with reported kcat 0.67 +/- 0.02 per second.
Respiratory complex II → Ubiquinone-1 source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]
experimental_model
Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
UQ1/DCIP are assay reagents; the isolated turnover value is not whole-cell ATP production.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The intact complex moves electrons from succinate into a quinone carrier.
primary_references
[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
tissue_or_cell_type
HEK293F-derived purified complex II
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 663–674
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft
### b2-met-human-complex-ii-succinate-quinone Purified human complex II coupled succinate oxidation to ubiquinone reduction in a UQ1/DCIP assay, with reported kcat 0.67 +/- 0.02 per second. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intact complex moves electrons from succinate into a quinone carrier. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: UQ1/DCIP are assay reagents; the isolated turnover value is not whole-cell ATP production. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
Complete structured claim and evidence
Wild-type human SDHAF2 coimmunoprecipitated SDHA from transfected HEK293 cells.
Human succinate dehydrogenase assembly factor 2 / SDHAF2 → SDHA source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 21, "char_start": 0, "char_end": 672, "evidence_access": "full-text"}]
experimental_model
Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Coimmunoprecipitation does not by itself establish the chemistry of FAD attachment.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The human assembly factor physically associated with the flavin-bearing subunit.
primary_references
[hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
tissue_or_cell_type
HEK293 cells
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–687
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. · source_derived_draft · unverified_draft
### b2-met-sdhaf2-sdha-binding Wild-type human SDHAF2 coimmunoprecipitated SDHA from transfected HEK293 cells. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human assembly factor physically associated with the flavin-bearing subunit. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. limitations: Coimmunoprecipitation does not by itself establish the chemistry of FAD attachment. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 21, "char_start": 0, "char_end": 672, "evidence_access": "full-text"}] [hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
Complete structured claim and evidence
Deleting yeast SDH5 eliminated detected covalent FAD attachment to Sdh1 even though Sdh1 protein remained present.
Saccharomyces cerevisiae sdh5 deletion → Saccharomyces cerevisiae Sdh1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 13, "char_start": 0, "char_end": 660, "evidence_access": "full-text"}]
experimental_model
Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue.
exposure
SDH5 deletion; SDS-PAGE FAD fluorescence and immunoblot.
limitations
Not proof of universal SDHAF2 requirement in mammalian cells.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Saccharomyces cerevisiae
plain_language
An assembly defect removed the cofactor attachment without simply removing all of the target protein.
primary_references
[hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
tissue_or_cell_type
Yeast mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 689–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. · source_derived_draft · unverified_draft
### b2-met-yeast-sdh5-flavination Deleting yeast SDH5 eliminated detected covalent FAD attachment to Sdh1 even though Sdh1 protein remained present. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An assembly defect removed the cofactor attachment without simply removing all of the target protein. organism: Saccharomyces cerevisiae tissue_or_cell_type: Yeast mitochondria experimental_model: Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. limitations: Not proof of universal SDHAF2 requirement in mammalian cells. exposure: SDH5 deletion; SDS-PAGE FAD fluorescence and immunoblot. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 13, "char_start": 0, "char_end": 660, "evidence_access": "full-text"}] [hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
Complete structured claim and evidence
Human SDHAF2 G78R failed to restore Sdh1 flavination in sdh5-null yeast, whereas wild-type human SDHAF2 restored it to about 77% of wild-type yeast.
Human SDHAF2 Gly78Arg → Saccharomyces cerevisiae Sdh1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 22, "char_start": 0, "char_end": 998, "evidence_access": "full-text"}]
experimental_model
Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue.
exposure
Expression from yeast SDH5 promoter; normalized FAD fluorescence.
limitations
Cross-species complementation; not a riboflavin-supplement rescue experiment.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein in Saccharomyces cerevisiae
plain_language
The inherited altered assembly factor failed a functional rescue test.
primary_references
[hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
tissue_or_cell_type
Yeast complementation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 702–713
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. · source_derived_draft · unverified_draft
### b2-met-sdhaf2-g78r-rescue Human SDHAF2 G78R failed to restore Sdh1 flavination in sdh5-null yeast, whereas wild-type human SDHAF2 restored it to about 77% of wild-type yeast. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inherited altered assembly factor failed a functional rescue test. organism: Homo sapiens protein in Saccharomyces cerevisiae tissue_or_cell_type: Yeast complementation experimental_model: Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. limitations: Cross-species complementation; not a riboflavin-supplement rescue experiment. exposure: Expression from yeast SDH5 promoter; normalized FAD fluorescence. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 22, "char_start": 0, "char_end": 998, "evidence_access": "full-text"}] [hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
Complete structured claim and evidence
SDHAF2 knockout and independent siRNA knockdown in MDA-MB-231 cells retained SDHA flavination; knockout cells also retained measurable SDH and succinate-quinone reductase activity.
Human SDHAF2 knockout state → SDHA source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC5076811", "locator": "HTML article p", "paragraph_index": 20, "char_start": 0, "char_end": 1274, "evidence_access": "full-text"}]
experimental_model
Human MDA-MB-231 breast cancer cells with CRISPR SDHAF2 disruption and independent siRNA knockdown.
exposure
CRISPR knockout, two independent siRNAs; FAD fluorescence/antibody and enzyme activity.
limitations
Cell-line-specific redundancy is not proof that SDHAF2 is dispensable in every tissue; contextual boundary to yeast and tumor findings.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This breast cancer cell model assembled active, flavinated complex II without SDHAF2.
primary_references
[bezawork-geleta-2016-sdhaf2] The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells (2016). https://pubmed.ncbi.nlm.nih.gov/27587393/ DOI: 10.1074/jbc.c116.755017
tissue_or_cell_type
MDA-MB-231 breast cancer cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 715–726
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MDA-MB-231 breast cancer cells with CRISPR SDHAF2 disruption and independent siRNA knockdown. · source_derived_draft · unverified_draft
### b2-met-sdhaf2-knockout-context-boundary SDHAF2 knockout and independent siRNA knockdown in MDA-MB-231 cells retained SDHA flavination; knockout cells also retained measurable SDH and succinate-quinone reductase activity. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This breast cancer cell model assembled active, flavinated complex II without SDHAF2. organism: Homo sapiens tissue_or_cell_type: MDA-MB-231 breast cancer cells experimental_model: Human MDA-MB-231 breast cancer cells with CRISPR SDHAF2 disruption and independent siRNA knockdown. limitations: Cell-line-specific redundancy is not proof that SDHAF2 is dispensable in every tissue; contextual boundary to yeast and tumor findings. exposure: CRISPR knockout, two independent siRNAs; FAD fluorescence/antibody and enzyme activity. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC5076811", "locator": "HTML article p", "paragraph_index": 20, "char_start": 0, "char_end": 1274, "evidence_access": "full-text"}] [bezawork-geleta-2016-sdhaf2] The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells (2016). https://pubmed.ncbi.nlm.nih.gov/27587393/ DOI: 10.1074/jbc.c116.755017
Complete structured claim and evidence
Human ETF crystal structure places its single FAD in a cleft shared by ETFA and ETFB, with most FAD contacts in the alpha-chain C-terminal region.
Human electron transfer flavoprotein / ETF → FAD source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC26136", "locator": "HTML article p", "paragraph_index": 30, "char_start": 0, "char_end": 1354, "evidence_access": "full-text"}]
experimental_model
Recombinant human ETFA/ETFB expressed in E. coli and crystallized at 2.1 Angstrom resolution.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Static structure; not a measurement of cellular cofactor availability.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
ETF is a two-protein electron shuttle carrying one B2-derived cofactor.
primary_references
[roberts-1996-human-etf] Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution (1996). https://pubmed.ncbi.nlm.nih.gov/8962055/ DOI: 10.1073/pnas.93.25.14355
tissue_or_cell_type
Recombinant protein expressed in E. coli
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 728–739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human ETFA/ETFB expressed in E. coli and crystallized at 2.1 Angstrom resolution. · source_derived_draft · unverified_draft
### b2-met-human-etf-fad-heterodimer Human ETF crystal structure places its single FAD in a cleft shared by ETFA and ETFB, with most FAD contacts in the alpha-chain C-terminal region. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF is a two-protein electron shuttle carrying one B2-derived cofactor. organism: Homo sapiens tissue_or_cell_type: Recombinant protein expressed in E. coli experimental_model: Recombinant human ETFA/ETFB expressed in E. coli and crystallized at 2.1 Angstrom resolution. limitations: Static structure; not a measurement of cellular cofactor availability. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC26136", "locator": "HTML article p", "paragraph_index": 30, "char_start": 0, "char_end": 1354, "evidence_access": "full-text"}] [roberts-1996-human-etf] Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution (1996). https://pubmed.ncbi.nlm.nih.gov/8962055/ DOI: 10.1073/pnas.93.25.14355
Complete structured claim and evidence
Human MCAD and ETF form an electron-transfer complex in which a recognition loop anchors binding while the ETF FAD domain samples electron-transfer-compatible conformations.
Human medium-chain acyl-CoA dehydrogenase / ACADM → Human electron transfer flavoprotein / ETF source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID15159392", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1430, "evidence_access": "primary-abstract"}]
experimental_model
Human ETF-MCAD complex crystallography and solution interfacial mutagenesis.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Primary abstract supports mechanism; no inference about clinical MCAD supplementation response.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Fatty-acid oxidation hands electrons from MCAD to a distinct ETF carrier.
primary_references
[toogood-2004-etf-mcad] Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex (2004). https://pubmed.ncbi.nlm.nih.gov/15159392/ DOI: 10.1074/jbc.m404884200
tissue_or_cell_type
Recombinant human protein complex
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ETF-MCAD complex crystallography and solution interfacial mutagenesis. · source_derived_draft · unverified_draft
### b2-met-mcad-etf-electron-transfer Human MCAD and ETF form an electron-transfer complex in which a recognition loop anchors binding while the ETF FAD domain samples electron-transfer-compatible conformations. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fatty-acid oxidation hands electrons from MCAD to a distinct ETF carrier. organism: Homo sapiens tissue_or_cell_type: Recombinant human protein complex experimental_model: Human ETF-MCAD complex crystallography and solution interfacial mutagenesis. limitations: Primary abstract supports mechanism; no inference about clinical MCAD supplementation response. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID15159392", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1430, "evidence_access": "primary-abstract"}] [toogood-2004-etf-mcad] Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex (2004). https://pubmed.ncbi.nlm.nih.gov/15159392/ DOI: 10.1074/jbc.m404884200
Complete structured claim and evidence
Interface mutagenesis and solution electron-transfer measurements supported a role for MCAD Glu212 and ETF alpha Arg249 interactions in productive electron transfer.
Human medium-chain acyl-CoA dehydrogenase / ACADM → Human electron transfer flavoprotein alpha / ETFA source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID15159392", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1430, "evidence_access": "primary-abstract"}]
experimental_model
Human ETF-MCAD complex crystallography and solution interfacial mutagenesis.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Residue interactions were inferred from combined structural/kinetic evidence; this is not a dietary-deficiency experiment.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Correct contact between the proteins matters as well as having the cofactor.
primary_references
[toogood-2004-etf-mcad] Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex (2004). https://pubmed.ncbi.nlm.nih.gov/15159392/ DOI: 10.1074/jbc.m404884200
tissue_or_cell_type
Recombinant protein interaction assays
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 754–765
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ETF-MCAD complex crystallography and solution interfacial mutagenesis. · source_derived_draft · unverified_draft
### b2-met-mcad-etf-interface Interface mutagenesis and solution electron-transfer measurements supported a role for MCAD Glu212 and ETF alpha Arg249 interactions in productive electron transfer. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correct contact between the proteins matters as well as having the cofactor. organism: Homo sapiens tissue_or_cell_type: Recombinant protein interaction assays experimental_model: Human ETF-MCAD complex crystallography and solution interfacial mutagenesis. limitations: Residue interactions were inferred from combined structural/kinetic evidence; this is not a dietary-deficiency experiment. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID15159392", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1430, "evidence_access": "primary-abstract"}] [toogood-2004-etf-mcad] Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex (2004). https://pubmed.ncbi.nlm.nih.gov/15159392/ DOI: 10.1074/jbc.m404884200
Complete structured claim and evidence
Porcine ETF-QO crystal structures resolved one FAD and one [4Fe-4S] cluster per protein, together with a separate ubiquinone-binding region.
Porcine electron transfer flavoprotein dehydrogenase → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}]
experimental_model
Purified porcine ETF-QO crystal structures with and without bound ubiquinone.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Static structure; the exact electron-entry sequence required additional functional experiments.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Sus scrofa
plain_language
ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF.
primary_references
[zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103
tissue_or_cell_type
Purified porcine mitochondrial ETF-QO
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–779
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified porcine ETF-QO crystal structures with and without bound ubiquinone. · source_derived_draft · unverified_draft
### b2-met-porcine-etfdh-cofactors Porcine ETF-QO crystal structures resolved one FAD and one [4Fe-4S] cluster per protein, together with a separate ubiquinone-binding region. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF. organism: Sus scrofa tissue_or_cell_type: Purified porcine mitochondrial ETF-QO experimental_model: Purified porcine ETF-QO crystal structures with and without bound ubiquinone. limitations: Static structure; the exact electron-entry sequence required additional functional experiments. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}] [zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103
Complete structured claim and evidence
Rhodobacter ETF-QO N338T and N338A lowered FAD redox potentials and quinone-reductase activity while minimally affecting ETF semiquinone disproportionation.
Rhodobacter ETF-QO N338T and N338A variants → Ubiquinone source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 2, "char_start": 0, "char_end": 1789, "evidence_access": "full-text"}]
experimental_model
Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.
exposure
Site-directed mutants compared with wild type.
limitations
Bacterial variant experiment; mechanism cannot be assigned quantitatively to human disease variants.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rhodobacter sphaeroides; human ETF/MCAD reagents
plain_language
Changing the flavin environment selectively impaired the quinone-reducing step.
primary_references
[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p
tissue_or_cell_type
Purified recombinant proteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 781–792
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft
### b2-met-etf-qo-fad-quinone-function Rhodobacter ETF-QO N338T and N338A lowered FAD redox potentials and quinone-reductase activity while minimally affecting ETF semiquinone disproportionation. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the flavin environment selectively impaired the quinone-reducing step. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified recombinant proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Bacterial variant experiment; mechanism cannot be assigned quantitatively to human disease variants. exposure: Site-directed mutants compared with wild type. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 2, "char_start": 0, "char_end": 1789, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p
Complete structured claim and evidence
Selective effects of ETF-QO FAD-site mutations supported electron entry from ETF through the [4Fe-4S] center, followed by flavin-mediated transfer to ubiquinone.
Rhodobacter sphaeroides ETF-QO → [4Fe-4S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct mechanistic integration of an iron-containing center with B2-derived FAD.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}]
experimental_model
Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rhodobacter sphaeroides; human ETF/MCAD reagents
plain_language
ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay.
primary_references
[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p
tissue_or_cell_type
Purified proteins
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 794–806
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft
### b2-met-etf-qo-iron-sulfur-entry Selective effects of ETF-QO FAD-site mutations supported electron entry from ETF through the [4Fe-4S] center, followed by flavin-mediated transfer to ubiquinone. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: Direct mechanistic integration of an iron-containing center with B2-derived FAD. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p
Complete structured claim and evidence
ETFDH variants associated with nonresponsive or partially responsive MADD showed severe misfolding in HEK-293 cells even in riboflavin-supplemented medium.
Human ETF-QO variants studied by Cornelius 2012 → Human electron transfer flavoprotein dehydrogenase / ETFDH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}]
experimental_model
Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.
exposure
Clinical-response-defined ETFDH variants; supplemented culture riboflavin.
limitations
Primary abstract-level claim; variants are grouped by this study, not a universal response classifier.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Some inherited ETF-QO defects remained severe despite greater B2 supply.
primary_references
[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175
tissue_or_cell_type
HEK-293 expression system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 808–819
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. · source_derived_draft · unverified_draft
### b2-met-etfdh-severe-rescue-boundary ETFDH variants associated with nonresponsive or partially responsive MADD showed severe misfolding in HEK-293 cells even in riboflavin-supplemented medium. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some inherited ETF-QO defects remained severe despite greater B2 supply. organism: Homo sapiens tissue_or_cell_type: HEK-293 expression system experimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. limitations: Primary abstract-level claim; variants are grouped by this study, not a universal response classifier. exposure: Clinical-response-defined ETFDH variants; supplemented culture riboflavin. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}] [cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175
Complete structured claim and evidence
Under the same supplemented culture conditions, ETF-QO variants linked to riboflavin-responsive MADD exhibited milder folding defects than the nonresponsive or partly responsive variants.
Human ETF-QO variants studied by Cornelius 2012 → Human electron transfer flavoprotein dehydrogenase / ETFDH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}]
experimental_model
Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.
exposure
Variant expression with supplemented riboflavin, comparing clinical response groups.
limitations
Response-associated molecular comparison; no dose recommendation and no claim that all missense variants respond.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Different inherited changes left different amounts of rescuable protein function.
primary_references
[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175
tissue_or_cell_type
HEK-293 expression system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 821–832
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. · source_derived_draft · unverified_draft
### b2-met-etfdh-responsive-milder-folding Under the same supplemented culture conditions, ETF-QO variants linked to riboflavin-responsive MADD exhibited milder folding defects than the nonresponsive or partly responsive variants. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different inherited changes left different amounts of rescuable protein function. organism: Homo sapiens tissue_or_cell_type: HEK-293 expression system experimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. limitations: Response-associated molecular comparison; no dose recommendation and no claim that all missense variants respond. exposure: Variant expression with supplemented riboflavin, comparing clinical response groups. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}] [cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175
Complete structured claim and evidence
Residual low thermal stability of the studied ETF-QO variants indicated that FAD availability did not fully correct their structural defects.
Human ETF-QO variants studied by Cornelius 2012 → Human electron transfer flavoprotein dehydrogenase / ETFDH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}]
experimental_model
Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.
exposure
Riboflavin and temperature variation in cell-expression experiments.
limitations
Does not determine clinical outcomes during fever or response of an untested mutation.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Cofactor support did not make the altered proteins structurally normal.
primary_references
[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175
tissue_or_cell_type
HEK-293-derived variant ETF-QO assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 834–845
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. · source_derived_draft · unverified_draft
### b2-met-etfdh-thermal-rescue-limit Residual low thermal stability of the studied ETF-QO variants indicated that FAD availability did not fully correct their structural defects. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor support did not make the altered proteins structurally normal. organism: Homo sapiens tissue_or_cell_type: HEK-293-derived variant ETF-QO assays experimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. limitations: Does not determine clinical outcomes during fever or response of an untested mutation. exposure: Riboflavin and temperature variation in cell-expression experiments. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}] [cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175
Complete structured claim and evidence
Purified human DLD I12T retained about 0.15 FAD per monomer versus approximately one in wild type, with forward and reverse activities of about 8% and 2%.
Human DLD Ile12Thr → FAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
DLD is reused from the B1 complexes; its flavin/NAD step is distinct from upstream thiamine diphosphate chemistry.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 19, "char_start": 0, "char_end": 871, "evidence_access": "full-text"}]
experimental_model
Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.
exposure
I12T mutagenesis, purified-protein FAD and activity assays.
limitations
Purification instability can affect measured occupancy; correlation does not prove FAD loss alone caused all activity loss.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This DLD variant poorly retained FAD and had very low catalytic activity.
primary_references
[szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
tissue_or_cell_type
Recombinant DLD expressed in E. coli
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 847–859
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. · source_derived_draft · unverified_draft
### b2-met-dld-i12t-fad-retention Purified human DLD I12T retained about 0.15 FAD per monomer versus approximately one in wild type, with forward and reverse activities of about 8% and 2%. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This DLD variant poorly retained FAD and had very low catalytic activity. organism: Homo sapiens tissue_or_cell_type: Recombinant DLD expressed in E. coli experimental_model: Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. limitations: Purification instability can affect measured occupancy; correlation does not prove FAD loss alone caused all activity loss. exposure: I12T mutagenesis, purified-protein FAD and activity assays. cross_nutrient: DLD is reused from the B1 complexes; its flavin/NAD step is distinct from upstream thiamine diphosphate chemistry. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 19, "char_start": 0, "char_end": 871, "evidence_access": "full-text"}] [szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
Complete structured claim and evidence
Human DLD G101del retained about 0.07 FAD per monomer in the recombinant preparation; size-exclusion analysis also indicated loss of its normal dimeric assembly.
Human DLD Gly101 deletion → FAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 5, "char_start": 0, "char_end": 502, "evidence_access": "full-text"}, {"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 6, "char_start": 0, "char_end": 1435, "evidence_access": "full-text"}]
experimental_model
Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.
exposure
G101del mutagenesis; FAD quantification and calibrated size exclusion.
limitations
Low expression and preparation heterogeneity were reported; no riboflavin-rescue experiment.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A different DLD alteration disrupted both flavin retention and protein assembly.
primary_references
[szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
tissue_or_cell_type
Purified recombinant DLD
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 861–872
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. · source_derived_draft · unverified_draft
### b2-met-dld-g101del-fad-retention Human DLD G101del retained about 0.07 FAD per monomer in the recombinant preparation; size-exclusion analysis also indicated loss of its normal dimeric assembly. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different DLD alteration disrupted both flavin retention and protein assembly. organism: Homo sapiens tissue_or_cell_type: Purified recombinant DLD experimental_model: Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. limitations: Low expression and preparation heterogeneity were reported; no riboflavin-rescue experiment. exposure: G101del mutagenesis; FAD quantification and calibrated size exclusion. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 5, "char_start": 0, "char_end": 502, "evidence_access": "full-text"}, {"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 6, "char_start": 0, "char_end": 1435, "evidence_access": "full-text"}] [szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
Complete structured claim and evidence
DLD activity in Slc25a32-null embryo mitochondria was about 23.9% of wild-type control.
Slc25a32-null mouse genotype → Mouse dihydrolipoamide dehydrogenase / Dld source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
DLD links B2 cofactor supply to glycine cleavage and thus folate-mediated one-carbon metabolism.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
Slc25a32-null versus wild-type embryos.
limitations
Knockout affects multiple flavoproteins; DLD-specific genetic rescue was not performed.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
A defect in mitochondrial flavin supply impaired the shared DLD enzyme.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Embryo mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 874–886
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-mouse-null-dld-activity DLD activity in Slc25a32-null embryo mitochondria was about 23.9% of wild-type control. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defect in mitochondrial flavin supply impaired the shared DLD enzyme. organism: Mus musculus tissue_or_cell_type: Embryo mitochondria experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Knockout affects multiple flavoproteins; DLD-specific genetic rescue was not performed. exposure: Slc25a32-null versus wild-type embryos. cross_nutrient: DLD links B2 cofactor supply to glycine cleavage and thus folate-mediated one-carbon metabolism. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Isolated Slc25a32-null embryo mitochondria produced about 10.6% of control labeled formate from [13C2]-glycine over 24 hours.
Slc25a32-null mouse genotype → Mitochondrial glycine-derived formate production source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B2-dependent mitochondrial function supports glycine carbon entry into folate-related one-carbon supply.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
Slc25a32-null mitochondria supplied [1,2-13C2]-glycine.
limitations
Long isolated-mitochondrial assay; this is glycine-derived flux, not total cellular formate synthesis.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
The same genetic defect sharply reduced one-carbon output from glycine.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Embryo mitochondria, 24-hour isotope incubation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 888–900
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-mouse-null-glycine-formate Isolated Slc25a32-null embryo mitochondria produced about 10.6% of control labeled formate from [13C2]-glycine over 24 hours. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same genetic defect sharply reduced one-carbon output from glycine. organism: Mus musculus tissue_or_cell_type: Embryo mitochondria, 24-hour isotope incubation experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Long isolated-mitochondrial assay; this is glycine-derived flux, not total cellular formate synthesis. exposure: Slc25a32-null mitochondria supplied [1,2-13C2]-glycine. cross_nutrient: B2-dependent mitochondrial function supports glycine carbon entry into folate-related one-carbon supply. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Maternal sodium formate supplementation increased embryo CH3-THF in Slc25a32-null offspring that completed neural tube closure.
Formate → 5-Methyltetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Demonstrates a formate-to-folate consequence downstream of a mitochondrial flavin-supply defect, not dietary folate deficiency.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 38, "char_start": 0, "char_end": 1062, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
Dams received 0.1 mol/L sodium formate in drinking water; experimental context only.
limitations
Analyzed responder subgroup; does not prove normal folate metabolism or bypass every effect of Slc25a32 loss.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Supplying a missing one-carbon donor changed the downstream folate profile.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Whole E11.5 embryos
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 902–914
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-formate-embryo-folate-rescue Maternal sodium formate supplementation increased embryo CH3-THF in Slc25a32-null offspring that completed neural tube closure. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying a missing one-carbon donor changed the downstream folate profile. organism: Mus musculus tissue_or_cell_type: Whole E11.5 embryos experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Analyzed responder subgroup; does not prove normal folate metabolism or bypass every effect of Slc25a32 loss. exposure: Dams received 0.1 mol/L sodium formate in drinking water; experimental context only. cross_nutrient: Demonstrates a formate-to-folate consequence downstream of a mitochondrial flavin-supply defect, not dietary folate deficiency. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 38, "char_start": 0, "char_end": 1062, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
After maternal sodium formate treatment, 14 of 16 Slc25a32-null embryos completed neural tube closure in the reported nine-litter experiment.
Formate → Embryonic neural tube closure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Connects a B2-related machinery defect to folate-dependent development through one-carbon availability.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 38, "char_start": 0, "char_end": 1062, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
0.1 mol/L sodium formate in dam drinking water; 73 total embryos, nine litters.
limitations
Small animal intervention; incomplete rescue and no human treatment inference.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
One-carbon supplementation partly bypassed a developmental consequence in this mouse model.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
E11.5 embryos
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 916–928
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-formate-embryo-neural-tube After maternal sodium formate treatment, 14 of 16 Slc25a32-null embryos completed neural tube closure in the reported nine-litter experiment. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One-carbon supplementation partly bypassed a developmental consequence in this mouse model. organism: Mus musculus tissue_or_cell_type: E11.5 embryos experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Small animal intervention; incomplete rescue and no human treatment inference. exposure: 0.1 mol/L sodium formate in dam drinking water; 73 total embryos, nine litters. cross_nutrient: Connects a B2-related machinery defect to folate-dependent development through one-carbon availability. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 38, "char_start": 0, "char_end": 1062, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Adding FAD directly to muscle enzyme assays fully restored the depressed SBCAD activity in the Slc25a32 mutant-mouse experiments.
FAD → Mouse short/branched-chain acyl-CoA dehydrogenase / Acadsb source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Flavin supply supports a distinct branched-chain amino-acid oxidation step.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 50, "char_start": 0, "char_end": 1147, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
FAD added directly to separate acyl-CoA dehydrogenase assays.
limitations
In vitro rescue differs from oral riboflavin response; the most pronounced enzyme defects occurred in K235R homozygotes.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
One amino-acid oxidation enzyme retained activity that could be restored by adding its cofactor.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Skeletal-muscle homogenates
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 930–942
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-mouse-sbcad-fad-rescue Adding FAD directly to muscle enzyme assays fully restored the depressed SBCAD activity in the Slc25a32 mutant-mouse experiments. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One amino-acid oxidation enzyme retained activity that could be restored by adding its cofactor. organism: Mus musculus tissue_or_cell_type: Skeletal-muscle homogenates experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: In vitro rescue differs from oral riboflavin response; the most pronounced enzyme defects occurred in K235R homozygotes. exposure: FAD added directly to separate acyl-CoA dehydrogenase assays. cross_nutrient: Flavin supply supports a distinct branched-chain amino-acid oxidation step. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 50, "char_start": 0, "char_end": 1147, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
FAD added to muscle assays only mildly improved depressed MCAD activity in Slc25a32 mutant mice; MCAD protein abundance was also lower in K235R homozygotes.
FAD → Mouse medium-chain acyl-CoA dehydrogenase / Acadm source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 50, "char_start": 0, "char_end": 1147, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
Direct FAD addition; independent MCAD activity and immunoblot readouts.
limitations
Activity and abundance are related observations, not proof that protein loss is the only cause of incomplete rescue.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
For MCAD, supplying cofactor alone could not promptly restore the missing enzyme capacity.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Skeletal-muscle homogenates
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 944–955
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-mouse-mcad-rescue-limit FAD added to muscle assays only mildly improved depressed MCAD activity in Slc25a32 mutant mice; MCAD protein abundance was also lower in K235R homozygotes. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: For MCAD, supplying cofactor alone could not promptly restore the missing enzyme capacity. organism: Mus musculus tissue_or_cell_type: Skeletal-muscle homogenates experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Activity and abundance are related observations, not proof that protein loss is the only cause of incomplete rescue. exposure: Direct FAD addition; independent MCAD activity and immunoblot readouts. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 50, "char_start": 0, "char_end": 1147, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
FAD added to muscle assays only mildly improved depressed VLCAD activity in Slc25a32 mutant mice; VLCAD abundance was lower in K235R homozygotes.
FAD → Mouse very-long-chain acyl-CoA dehydrogenase / Acadvl source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 50, "char_start": 0, "char_end": 1147, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
Direct FAD addition; VLCAD measured separately from MCAD.
limitations
This does not establish the response of genetic ACADVL disease to riboflavin.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
The long-chain oxidation enzyme also had limitations beyond immediately available free cofactor.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Skeletal-muscle homogenates
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 957–968
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-mouse-vlcad-rescue-limit FAD added to muscle assays only mildly improved depressed VLCAD activity in Slc25a32 mutant mice; VLCAD abundance was lower in K235R homozygotes. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long-chain oxidation enzyme also had limitations beyond immediately available free cofactor. organism: Mus musculus tissue_or_cell_type: Skeletal-muscle homogenates experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: This does not establish the response of genetic ACADVL disease to riboflavin. exposure: Direct FAD addition; VLCAD measured separately from MCAD. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 50, "char_start": 0, "char_end": 1147, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Three-day riboflavin starvation of mouse B16 cells reduced proteomic clusters associated with electron transport and ATP synthesis.
Riboflavin (vitamin B2) → Respiratory-chain protein abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}]
experimental_model
Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics.
exposure
Riboflavin-free culture for three days; quantitative proteomics.
limitations
Abundance, not direct pathway flux; cancer-cell dependence may differ from normal cells.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Removing B2 lowered the abundance of respiratory machinery in these tumor cells.
primary_references
[martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5
tissue_or_cell_type
B16 melanoma cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 970–981
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. · source_derived_draft · unverified_draft
### b2-met-b16-respiratory-proteome Three-day riboflavin starvation of mouse B16 cells reduced proteomic clusters associated with electron transport and ATP synthesis. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing B2 lowered the abundance of respiratory machinery in these tumor cells. organism: Mus musculus tissue_or_cell_type: B16 melanoma cells experimental_model: Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. limitations: Abundance, not direct pathway flux; cancer-cell dependence may differ from normal cells. exposure: Riboflavin-free culture for three days; quantitative proteomics. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}] [martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5
Complete structured claim and evidence
Eight glycolytic enzymes increased in abundance after three days of riboflavin starvation in B16 melanoma cells.
Riboflavin (vitamin B2) → Glycolytic enzyme abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}]
experimental_model
Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics.
exposure
Three-day riboflavin withdrawal; mass-spectrometry proteomics.
limitations
The response does not demonstrate complete energetic compensation or measured glycolytic flux.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
These cells increased glycolytic machinery while their respiratory machinery declined.
primary_references
[martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5
tissue_or_cell_type
B16 melanoma cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 983–994
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. · source_derived_draft · unverified_draft
### b2-met-b16-glycolytic-proteome Eight glycolytic enzymes increased in abundance after three days of riboflavin starvation in B16 melanoma cells. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: These cells increased glycolytic machinery while their respiratory machinery declined. organism: Mus musculus tissue_or_cell_type: B16 melanoma cells experimental_model: Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. limitations: The response does not demonstrate complete energetic compensation or measured glycolytic flux. exposure: Three-day riboflavin withdrawal; mass-spectrometry proteomics. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}] [martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5
Complete structured claim and evidence
Native mass spectrometry and crystallography identified FAD bound to recombinant human MTHFR catalytic domains.
FAD → Methylenetetrahydrofolate reductase / MTHFR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD supports a folate-processing enzyme.
evidence_location
Results: kinetics, FAD occupancy and SAM inhibition; Table 1; Figs 2-4, 6
experimental_model
Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
MTHFR carries a B2-derived FAD cofactor.
primary_references
[froese2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 996–1008
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays. · source_derived_draft · unverified_draft
### b2-mthfr-fad-occupancy Native mass spectrometry and crystallography identified FAD bound to recombinant human MTHFR catalytic domains. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTHFR carries a B2-derived FAD cofactor. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-FAD supports a folate-processing enzyme. evidence_location: Results: kinetics, FAD occupancy and SAM inhibition; Table 1; Figs 2-4, 6 [froese2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
Complete structured claim and evidence
HPLC assays measured human MTHFR reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using NADPH.
Methylenetetrahydrofolate reductase / MTHFR → 5-Methyltetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD, folate and nicotinamide-containing NADPH participate in one reaction.
evidence_location
Results: kinetics, FAD occupancy and SAM inhibition; Table 1; Figs 2-4, 6
experimental_model
Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The enzyme makes the methylfolate used in homocysteine recycling.
primary_references
[froese2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1010–1022
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays. · source_derived_draft · unverified_draft
### b2-mthfr-methylfolate-production HPLC assays measured human MTHFR reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using NADPH. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme makes the methylfolate used in homocysteine recycling. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-FAD, folate and nicotinamide-containing NADPH participate in one reaction. evidence_location: Results: kinetics, FAD occupancy and SAM inhibition; Table 1; Figs 2-4, 6 [froese2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
Complete structured claim and evidence
SAM inhibited recombinant human MTHFR; phosphorylated protein was more sensitive to this inhibition than phosphatase-treated protein.
S-Adenosyl-L-methionine → Methylenetetrahydrofolate reductase / MTHFR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Methionine/SAM feedback regulates the B2-dependent folate step.
evidence_location
Results: kinetics, FAD occupancy and SAM inhibition; Table 1; Figs 2-4, 6
experimental_model
Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays.
exposure
Purified-enzyme assay
limitations
In-vitro regulation; phosphorylation itself did not materially reduce catalytic turnover in this assay.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A methionine-cycle product regulates methylfolate production.
primary_references
[froese2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1024–1036
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays. · source_derived_draft · unverified_draft
### b2-mthfr-sam-inhibition SAM inhibited recombinant human MTHFR; phosphorylated protein was more sensitive to this inhibition than phosphatase-treated protein. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A methionine-cycle product regulates methylfolate production. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTHFR expressed in Sf9 cells; mass spectrometry, 2.5-A structure, HPLC activity assays. limitations: In-vitro regulation; phosphorylation itself did not materially reduce catalytic turnover in this assay. exposure: Purified-enzyme assay cross_nutrient: Methionine/SAM feedback regulates the B2-dependent folate step. evidence_location: Results: kinetics, FAD occupancy and SAM inhibition; Table 1; Figs 2-4, 6 [froese2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
Complete structured claim and evidence
Ala222Val MTHFR released FAD about three times faster than wild type after dilution; concentration dependence supported dimer dissociation before cofactor loss.
MTHFR Ala222Val protein → FAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Genetic variation modifies retention of the B2-derived cofactor at a folate enzyme.
evidence_location
Results: FAD loss; Figs 1-3
experimental_model
Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays.
exposure
Purified-enzyme assay
limitations
The diluted purified-protein experiment does not measure intracellular cofactor occupancy in every 677TT carrier.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This variant loses its cofactor more readily in the dilution experiment.
primary_references
[yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1038–1050
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. · source_derived_draft · unverified_draft
### b2-mthfr-ala222val-fad-loss Ala222Val MTHFR released FAD about three times faster than wild type after dilution; concentration dependence supported dimer dissociation before cofactor loss. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant loses its cofactor more readily in the dilution experiment. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. limitations: The diluted purified-protein experiment does not measure intracellular cofactor occupancy in every 677TT carrier. exposure: Purified-enzyme assay cross_nutrient: Genetic variation modifies retention of the B2-derived cofactor at a folate enzyme. evidence_location: Results: FAD loss; Figs 1-3 [yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
Complete structured claim and evidence
Methyltetrahydrofolate slowed FAD loss from diluted Ala222Val MTHFR in the tested concentration series.
5-Methyltetrahydrofolate → MTHFR Ala222Val protein source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Folate binding can stabilize a B2-derived cofactor interaction.
evidence_location
Results: FAD loss; Figs 1-3
experimental_model
Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays.
exposure
Purified-enzyme assay
limitations
Protein-stability assay; clinical folate or riboflavin treatment effects were not tested here.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Folate product helped the variant retain FAD in vitro.
primary_references
[yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1052–1064
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. · source_derived_draft · unverified_draft
### b2-methylfolate-mthfr-retention Methyltetrahydrofolate slowed FAD loss from diluted Ala222Val MTHFR in the tested concentration series. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate product helped the variant retain FAD in vitro. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. limitations: Protein-stability assay; clinical folate or riboflavin treatment effects were not tested here. exposure: Purified-enzyme assay cross_nutrient: Folate binding can stabilize a B2-derived cofactor interaction. evidence_location: Results: FAD loss; Figs 1-3 [yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
Complete structured claim and evidence
SAM slowed FAD dissociation after MTHFR dilution, including Ala222Val, despite its separate reversible inhibition of catalytic activity.
S-Adenosyl-L-methionine → MTHFR Ala222Val protein source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Methionine-cycle feedback affects both folate-enzyme activity and B2-cofactor retention.
evidence_location
Results: FAD loss; Figs 1-3
experimental_model
Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays.
exposure
Purified-enzyme assay
limitations
In-vitro effects; stabilization is not equivalent to increased reaction flux.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Cofactor retention and catalytic speed respond differently to SAM.
primary_references
[yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1066–1078
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. · source_derived_draft · unverified_draft
### b2-sam-mthfr-retention SAM slowed FAD dissociation after MTHFR dilution, including Ala222Val, despite its separate reversible inhibition of catalytic activity. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor retention and catalytic speed respond differently to SAM. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. limitations: In-vitro effects; stabilization is not equivalent to increased reaction flux. exposure: Purified-enzyme assay cross_nutrient: Methionine-cycle feedback affects both folate-enzyme activity and B2-cofactor retention. evidence_location: Results: FAD loss; Figs 1-3 [yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
Complete structured claim and evidence
Glu429Ala MTHFR showed FAD-release behavior indistinguishable from wild type under the tested dilution conditions.
MTHFR Glu429Ala protein → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Bounds extrapolation of B2-cofactor loss across MTHFR variants.
evidence_location
Results: FAD loss; Figs 1-3
experimental_model
Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays.
exposure
Purified-enzyme assay
limitations
Normal result under tested in-vitro conditions does not exclude all cellular effects of A1298C.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The two common MTHFR variants did not share the same cofactor-retention phenotype.
primary_references
[yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1080–1092
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. · source_derived_draft · unverified_draft
### b2-mthfr-glu429ala-retention Glu429Ala MTHFR showed FAD-release behavior indistinguishable from wild type under the tested dilution conditions. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two common MTHFR variants did not share the same cofactor-retention phenotype. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays. limitations: Normal result under tested in-vitro conditions does not exclude all cellular effects of A1298C. exposure: Purified-enzyme assay cross_nutrient: Bounds extrapolation of B2-cofactor loss across MTHFR variants. evidence_location: Results: FAD loss; Figs 1-3 [yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998
Complete structured claim and evidence
Purified recombinant human MTRR contained equimolar FAD and FMN, identifying two distinct flavin cofactors in the same reductase.
Methionine synthase reductase / MTRR → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived flavins form part of the B12-reactivation machinery.
evidence_location
Abstract
experimental_model
Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
MTRR uses both B2-derived cofactors.
primary_references
[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1094–1106
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft
### b2-mtrr-dual-flavins Purified recombinant human MTRR contained equimolar FAD and FMN, identifying two distinct flavin cofactors in the same reductase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTRR uses both B2-derived cofactors. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-derived flavins form part of the B12-reactivation machinery. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
Complete structured claim and evidence
NADPH reduction of purified MTRR generated an air-stable flavin semiquinone detected spectroscopically.
NADPH → Methionine synthase reductase / MTRR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinamide-containing NADPH supplies electrons to B2-derived flavins.
evidence_location
Abstract
experimental_model
Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
NADPH provides electrons to the flavin-containing reductase.
primary_references
[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1108–1120
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft
### b2-mtrr-nadph-reduction NADPH reduction of purified MTRR generated an air-stable flavin semiquinone detected spectroscopically. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NADPH provides electrons to the flavin-containing reductase. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: Nicotinamide-containing NADPH supplies electrons to B2-derived flavins. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
Complete structured claim and evidence
Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.
Methionine synthase reductase / MTRR → Cobalamin-dependent methionine synthase / MTR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism.
evidence_location
Abstract
experimental_model
Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
exposure
Purified-enzyme assay
limitations
Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The flavin reductase helps restore an enzyme that uses B12 and methylfolate.
primary_references
[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1122–1134
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft
### b2-mtrr-mtr-reactivation Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin reductase helps restore an enzyme that uses B12 and methylfolate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested. exposure: Purified-enzyme assay cross_nutrient: B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
Complete structured claim and evidence
The human PNPO structure localized tightly bound FMN at the conserved catalytic site of the homodimer.
Flavin mononucleotide → Pyridoxine 5-prime-phosphate oxidase / PNPO source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FMN is a cofactor for B6 activation.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
PNPO uses the FMN form of vitamin B2.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1136–1148
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnpo-fmn-binding The human PNPO structure localized tightly bound FMN at the conserved catalytic site of the homodimer. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PNPO uses the FMN form of vitamin B2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-FMN is a cofactor for B6 activation. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
Purified human PNPO converted PNP to PLP with a turnover number of 0.19 per second at 37 C.
Pyridoxine 5-prime-phosphate oxidase / PNPO → Pyridoxine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-dependent oxidation activates one B6 precursor.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
PNPO changes phosphorylated pyridoxine into active B6.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1150–1162
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnpo-pnp-oxidation Purified human PNPO converted PNP to PLP with a turnover number of 0.19 per second at 37 C. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PNPO changes phosphorylated pyridoxine into active B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-dependent oxidation activates one B6 precursor. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
Human PNPO also converted PMP to PLP, with a turnover number of 0.20 per second at 37 C.
Pyridoxine 5-prime-phosphate oxidase / PNPO → Pyridoxamine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
A second B6 precursor depends on the FMN enzyme.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Phosphorylated pyridoxamine enters the same activation enzyme.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1164–1176
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnpo-pmp-oxidation Human PNPO also converted PMP to PLP, with a turnover number of 0.20 per second at 37 C. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphorylated pyridoxamine enters the same activation enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: A second B6 precursor depends on the FMN enzyme. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
PLP competitively inhibited purified human PNPO in the reported kinetic assays.
PLP → Pyridoxine 5-prime-phosphate oxidase / PNPO source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-product feedback regulates a B2-dependent enzyme.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
The paper did not establish free PLP pools or inhibition magnitude in intact mammalian tissues.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The active B6 product can slow its own formation in vitro.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1178–1190
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnp-product-inhibition PLP competitively inhibited purified human PNPO in the reported kinetic assays. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active B6 product can slow its own formation in vitro. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: The paper did not establish free PLP pools or inhibition magnitude in intact mammalian tissues. exposure: Purified-enzyme assay cross_nutrient: B6-product feedback regulates a B2-dependent enzyme. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
Human PDXK assays directly measured ATP-dependent conversion of pyridoxal to PLP, a reaction distinct from PNPO oxidation.
Pyridoxal kinase / PDXK → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Separates the B6 phosphorylation step from the B2-dependent oxidation step.
evidence_location
Abstract
experimental_model
Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures.
exposure
Purified-enzyme assay
limitations
This biochemical route does not establish that dietary pyridoxal bypasses all consequences of PNPO disease.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Not every route to active B6 passes through PNPO.
primary_references
[safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1192–1204
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures. · source_derived_draft · unverified_draft
### b2-pdxk-pyridoxal-route Human PDXK assays directly measured ATP-dependent conversion of pyridoxal to PLP, a reaction distinct from PNPO oxidation. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every route to active B6 passes through PNPO. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures. limitations: This biochemical route does not establish that dietary pyridoxal bypasses all consequences of PNPO disease. exposure: Purified-enzyme assay cross_nutrient: Separates the B6 phosphorylation step from the B2-dependent oxidation step. evidence_location: Abstract [safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107
Complete structured claim and evidence
R229W PNPO had an FMN dissociation constant approximately 50-fold higher than wild type in apoenzyme fluorescence titrations.
PNPO Arg229Trp protein → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
A B6-activation disorder directly disrupts B2-cofactor binding.
evidence_location
Results: Table 3 and Fig 1; Table 2 and Fig 2
experimental_model
Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The genetic substitution weakens FMN binding.
primary_references
[musayev2009] Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. (2009). https://pubmed.ncbi.nlm.nih.gov/19759001/ DOI: 10.1074/jbc.m109.038372
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1206–1218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure. · source_derived_draft · unverified_draft
### b2-pnpo-r229w-fmn-affinity R229W PNPO had an FMN dissociation constant approximately 50-fold higher than wild type in apoenzyme fluorescence titrations. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The genetic substitution weakens FMN binding. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: A B6-activation disorder directly disrupts B2-cofactor binding. evidence_location: Results: Table 3 and Fig 1; Table 2 and Fig 2 [musayev2009] Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. (2009). https://pubmed.ncbi.nlm.nih.gov/19759001/ DOI: 10.1074/jbc.m109.038372
Complete structured claim and evidence
R229W PNPO showed approximately 850-fold lower PNP catalytic efficiency, combining a 192-fold higher Km and 4.5-fold lower kcat.
PNPO Arg229Trp protein → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B2-cofactor binding is one part of a broader genetic defect in B6 activation.
evidence_location
Results: Table 3 and Fig 1; Table 2 and Fig 2
experimental_model
Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure.
exposure
Purified-enzyme assay
limitations
Km is a kinetic parameter, not a direct binding constant; adding FMN alone was not shown to normalize this whole defect.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The defect also changes substrate handling and reaction speed.
primary_references
[musayev2009] Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. (2009). https://pubmed.ncbi.nlm.nih.gov/19759001/ DOI: 10.1074/jbc.m109.038372
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1220–1232
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure. · source_derived_draft · unverified_draft
### b2-pnpo-r229w-catalytic-efficiency R229W PNPO showed approximately 850-fold lower PNP catalytic efficiency, combining a 192-fold higher Km and 4.5-fold lower kcat. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect also changes substrate handling and reaction speed. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure. limitations: Km is a kinetic parameter, not a direct binding constant; adding FMN alone was not shown to normalize this whole defect. exposure: Purified-enzyme assay cross_nutrient: B2-cofactor binding is one part of a broader genetic defect in B6 activation. evidence_location: Results: Table 3 and Fig 1; Table 2 and Fig 2 [musayev2009] Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. (2009). https://pubmed.ncbi.nlm.nih.gov/19759001/ DOI: 10.1074/jbc.m109.038372
Complete structured claim and evidence
Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar.
Human kynurenine 3-monooxygenase / KMO → L-Kynurenine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD and nicotinamide-containing NADPH support a branch upstream of de novo niacin synthesis.
evidence_location
Fig 2f and Methods: kinetic assays; interpret species separately
experimental_model
Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography.
exposure
Purified-enzyme assay
limitations
Human functional assays and bacterial structures are distinct evidence; this experiment did not test dietary B2 restriction or total NAD synthesis.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A flavin enzyme directs tryptophan-derived kynurenine into the hydroxylated branch.
primary_references
[hutchinson2017] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. (2017). https://pubmed.ncbi.nlm.nih.gov/28604669/ DOI: 10.1038/ncomms15827
tissue_or_cell_type
Sf9 membrane fraction expressing human KMO
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1234–1246
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography. · source_derived_draft · unverified_draft
### b2-kmo-kynurenine-hydroxylation Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A flavin enzyme directs tryptophan-derived kynurenine into the hydroxylated branch. organism: Homo sapiens tissue_or_cell_type: Sf9 membrane fraction expressing human KMO experimental_model: Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography. limitations: Human functional assays and bacterial structures are distinct evidence; this experiment did not test dietary B2 restriction or total NAD synthesis. exposure: Purified-enzyme assay cross_nutrient: B2-FAD and nicotinamide-containing NADPH support a branch upstream of de novo niacin synthesis. evidence_location: Fig 2f and Methods: kinetic assays; interpret species separately [hutchinson2017] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. (2017). https://pubmed.ncbi.nlm.nih.gov/28604669/ DOI: 10.1038/ncomms15827
Complete structured claim and evidence
Kmo knockout reduced quinolinate to about 3% of wild-type liver content but about 80% of wild-type brain content.
Mouse kynurenine 3-monooxygenase / Kmo → Quinolinic acid source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
A B2-dependent step feeds the tryptophan-to-niacin pathway with tissue-specific dependence.
evidence_location
Results: liver Fig 4 and brain Fig 7; matching abstract conclusion
experimental_model
Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays.
exposure
Constitutive Kmo deletion
limitations
Genetic deletion; alternative routes were proposed but not all directly traced.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Removing this enzyme affected downstream metabolites differently across tissues.
primary_references
[giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
tissue_or_cell_type
Liver and brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1248–1260
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. · source_derived_draft · unverified_draft
### b2-kmo-loss-quinolinate-tissue Kmo knockout reduced quinolinate to about 3% of wild-type liver content but about 80% of wild-type brain content. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing this enzyme affected downstream metabolites differently across tissues. organism: Mus musculus tissue_or_cell_type: Liver and brain experimental_model: Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. limitations: Genetic deletion; alternative routes were proposed but not all directly traced. exposure: Constitutive Kmo deletion cross_nutrient: A B2-dependent step feeds the tryptophan-to-niacin pathway with tissue-specific dependence. evidence_location: Results: liver Fig 4 and brain Fig 7; matching abstract conclusion [giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
Complete structured claim and evidence
Measured liver and brain NAD+ contents were not significantly different between Kmo-knockout and wild-type mice.
Mouse kynurenine 3-monooxygenase / Kmo → NAD+ source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Bounds the B2-KMO-niacin link: a cofactor-dependent pathway step is not proof that total NAD pools must fall.
evidence_location
Results: liver Fig 4 and brain Fig 7; matching abstract conclusion
experimental_model
Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays.
exposure
Constitutive Kmo deletion
limitations
Steady-state pools do not measure de novo synthesis flux; diet and salvage can affect the result.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Losing the KMO branch did not collapse the measured NAD+ pools.
primary_references
[giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
tissue_or_cell_type
Liver and brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1262–1274
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. · source_derived_draft · unverified_draft
### b2-kmo-loss-nad-preserved Measured liver and brain NAD+ contents were not significantly different between Kmo-knockout and wild-type mice. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the KMO branch did not collapse the measured NAD+ pools. organism: Mus musculus tissue_or_cell_type: Liver and brain experimental_model: Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. limitations: Steady-state pools do not measure de novo synthesis flux; diet and salvage can affect the result. exposure: Constitutive Kmo deletion cross_nutrient: Bounds the B2-KMO-niacin link: a cofactor-dependent pathway step is not proof that total NAD pools must fall. evidence_location: Results: liver Fig 4 and brain Fig 7; matching abstract conclusion [giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
Complete structured claim and evidence
Riboflavin-deficient baboons excreted approximately one tenth as much urinary 3-hydroxykynurenine in the reported dietary comparison.
Riboflavin (vitamin B2) → 3-Hydroxy-L-kynurenine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Dietary B2 status influences a tryptophan/niacin-pathway readout.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements.
exposure
Experimental riboflavin-deficient diet
limitations
Indexed abstract does not give diet duration or group size; urinary output is not a direct tissue KMO flux measurement.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Papio species (baboon)
plain_language
Dietary B2 deficiency changed a measured tryptophan-pathway product.
primary_references
[verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/
tissue_or_cell_type
Urine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1276–1288
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. · source_derived_draft · unverified_draft
### b2-baboon-urinary-hydroxykynurenine Riboflavin-deficient baboons excreted approximately one tenth as much urinary 3-hydroxykynurenine in the reported dietary comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary B2 deficiency changed a measured tryptophan-pathway product. organism: Papio species (baboon) tissue_or_cell_type: Urine experimental_model: Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. limitations: Indexed abstract does not give diet duration or group size; urinary output is not a direct tissue KMO flux measurement. exposure: Experimental riboflavin-deficient diet cross_nutrient: Dietary B2 status influences a tryptophan/niacin-pathway readout. evidence_location: Abstract [verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/
Complete structured claim and evidence
Red-cell pyridine nucleotides decreased in pyridoxine-deficient baboons, but not in the riboflavin-deficient group.
Riboflavin (vitamin B2) → Erythrocyte pyridine nucleotide content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Prevents equating altered tryptophan metabolism with universal niacin depletion.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements.
exposure
Experimental riboflavin-deficient diet
limitations
The abstract reports an aggregate red-cell readout; it does not resolve synthesis flux, other tissues or every NAD species.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Papio species (baboon)
plain_language
The B2-related urine change did not establish a fall in this red-cell nucleotide pool.
primary_references
[verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/
tissue_or_cell_type
Erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1290–1302
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. · source_derived_draft · unverified_draft
### b2-baboon-pyridine-nucleotide-boundary Red-cell pyridine nucleotides decreased in pyridoxine-deficient baboons, but not in the riboflavin-deficient group. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B2-related urine change did not establish a fall in this red-cell nucleotide pool. organism: Papio species (baboon) tissue_or_cell_type: Erythrocytes experimental_model: Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. limitations: The abstract reports an aggregate red-cell readout; it does not resolve synthesis flux, other tissues or every NAD species. exposure: Experimental riboflavin-deficient diet cross_nutrient: Prevents equating altered tryptophan metabolism with universal niacin depletion. evidence_location: Abstract [verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/
Complete structured claim and evidence
Human GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling.
NADPH → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinamide-containing NADPH and B2-derived FAD perform distinct functions.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
Structural support for the established catalytic cycle; radiation reduction must be distinguished from natural catalysis.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
NADPH supplies electrons to the B2-derived cofactor.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human erythrocyte-type GSR crystals
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1304–1316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-nadph-to-fad Human GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NADPH supplies electrons to the B2-derived cofactor. organism: Homo sapiens tissue_or_cell_type: Purified human erythrocyte-type GSR crystals experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: Structural support for the established catalytic cycle; radiation reduction must be distinguished from natural catalysis. exposure: Purified-enzyme assay cross_nutrient: Nicotinamide-containing NADPH and B2-derived FAD perform distinct functions. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
The GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction.
FAD → Glutathione reductase / GSR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived cofactor bridges NADPH and the glutathione system.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
Mechanism integrates natural-substrate structures with prior kinetic work; transient intermediates were not all directly trapped here.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
FAD relays electrons through enzyme cysteines.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human GSR
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1318–1330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-flavin-disulfide-relay The GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FAD relays electrons through enzyme cysteines. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: Mechanism integrates natural-substrate structures with prior kinetic work; transient intermediates were not all directly trapped here. exposure: Purified-enzyme assay cross_nutrient: B2-derived cofactor bridges NADPH and the glutathione system. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay.
Glutathione reductase / GSR → GSSG source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This enzyme recycles glutathione after oxidation.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human GSR
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1332–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-gssg-to-gsh GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme recycles glutathione after oxidation. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion. exposure: Purified-enzyme assay cross_nutrient: B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
The rat TXNRD1 Sec498Cys structure showed conserved FAD- and NADPH-binding architecture around the N-terminal redox center.
FAD → Rat thioredoxin reductase 1 / Txnrd1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD and nicotinamide cofactors provide the upstream side of a selenium-containing reductase.
evidence_location
Abstract
experimental_model
Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation.
exposure
Purified-enzyme assay
limitations
Structure used a Sec-to-Cys mutant and oxidized NADP+; direct atom-level conclusions about wild-type selenium chemistry are limited.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus protein expressed recombinantly
plain_language
Thioredoxin reductase has a flavin input side.
primary_references
[sandalova2001] Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. (2001). https://pubmed.ncbi.nlm.nih.gov/11481439/ DOI: 10.1073/pnas.171178698
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1346–1358
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation. · source_derived_draft · unverified_draft
### b2-txnrd1-fad-nadph-architecture The rat TXNRD1 Sec498Cys structure showed conserved FAD- and NADPH-binding architecture around the N-terminal redox center. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thioredoxin reductase has a flavin input side. organism: Rattus norvegicus protein expressed recombinantly tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation. limitations: Structure used a Sec-to-Cys mutant and oxidized NADP+; direct atom-level conclusions about wild-type selenium chemistry are limited. exposure: Purified-enzyme assay cross_nutrient: B2-FAD and nicotinamide cofactors provide the upstream side of a selenium-containing reductase. evidence_location: Abstract [sandalova2001] Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. (2001). https://pubmed.ncbi.nlm.nih.gov/11481439/ DOI: 10.1073/pnas.171178698
Complete structured claim and evidence
A rat TXNRD1 structure and docking model with human thioredoxin support a relay through the opposite subunit and C-terminal tail toward the substrate.
Rat thioredoxin reductase 1 / Txnrd1 → TXN1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-dependent electron input and selenium-containing terminal chemistry are separate serial steps.
evidence_location
Abstract
experimental_model
Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation.
exposure
Purified-enzyme assay
limitations
Human thioredoxin was docked onto the rat Sec498Cys structure (Fig 6); the complex and cross-species turnover were not measured.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus reductase and Homo sapiens thioredoxin docking partner
plain_language
A second redox center carries electrons onward to thioredoxin.
primary_references
[sandalova2001] Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. (2001). https://pubmed.ncbi.nlm.nih.gov/11481439/ DOI: 10.1073/pnas.171178698
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1360–1372
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation. · source_derived_draft · unverified_draft
### b2-txnrd1-terminal-relay A rat TXNRD1 structure and docking model with human thioredoxin support a relay through the opposite subunit and C-terminal tail toward the substrate. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second redox center carries electrons onward to thioredoxin. organism: Rattus norvegicus reductase and Homo sapiens thioredoxin docking partner tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation. limitations: Human thioredoxin was docked onto the rat Sec498Cys structure (Fig 6); the complex and cross-species turnover were not measured. exposure: Purified-enzyme assay cross_nutrient: B2-dependent electron input and selenium-containing terminal chemistry are separate serial steps. evidence_location: Abstract [sandalova2001] Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. (2001). https://pubmed.ncbi.nlm.nih.gov/11481439/ DOI: 10.1073/pnas.171178698
Complete structured claim and evidence
Engineered rat TXNRD1 terminal mutants retained one FAD per subunit and rapidly formed a thiolate-flavin charge-transfer signal upon NADPH titration.
Rat TXNRD1 Sec498Cys protein → FAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Distinct B2-cofactor and selenium-site functions cannot substitute for one another.
evidence_location
Abstract
experimental_model
Rat TXNRD1 Sec498Cys, Sec498Ser and C-terminal truncation expressed in E. coli; FAD analysis, NADPH titration and thioredoxin assays.
exposure
Purified-enzyme assay
limitations
Includes Sec498Cys, Sec498Ser and terminal truncation; engineered proteins, not nutrient-depleted animals.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus protein expressed in Escherichia coli
plain_language
A defective terminal center can leave upstream flavin reduction intact.
primary_references
[zhong2000] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1374–1386
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat TXNRD1 Sec498Cys, Sec498Ser and C-terminal truncation expressed in E. coli; FAD analysis, NADPH titration and thioredoxin assays. · source_derived_draft · unverified_draft
### b2-txnrd-mutants-upstream-retained Engineered rat TXNRD1 terminal mutants retained one FAD per subunit and rapidly formed a thiolate-flavin charge-transfer signal upon NADPH titration. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defective terminal center can leave upstream flavin reduction intact. organism: Rattus norvegicus protein expressed in Escherichia coli tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Rat TXNRD1 Sec498Cys, Sec498Ser and C-terminal truncation expressed in E. coli; FAD analysis, NADPH titration and thioredoxin assays. limitations: Includes Sec498Cys, Sec498Ser and terminal truncation; engineered proteins, not nutrient-depleted animals. exposure: Purified-enzyme assay cross_nutrient: Distinct B2-cofactor and selenium-site functions cannot substitute for one another. evidence_location: Abstract [zhong2000] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200
Complete structured claim and evidence
Replacing rat TXNRD1 Sec498 with cysteine lowered thioredoxin-reduction kcat about 100-fold; serine substitution and terminal truncation lacked detectable activity.
Rat TXNRD1 Sec498Cys protein → Thioredoxin proteins source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B2-derived FAD cannot replace the selenium-containing catalytic residue.
evidence_location
Abstract
experimental_model
Rat TXNRD1 Sec498Cys, Sec498Ser and C-terminal truncation expressed in E. coli; FAD analysis, NADPH titration and thioredoxin assays.
exposure
Purified-enzyme assay
limitations
Assay-substrate species is unresolved in accessible source details; engineered proteins do not establish dietary B2-by-selenium synergy.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus protein expressed in Escherichia coli
plain_language
Flavin retention did not preserve efficient thioredoxin reduction.
primary_references
[zhong2000] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1388–1400
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat TXNRD1 Sec498Cys, Sec498Ser and C-terminal truncation expressed in E. coli; FAD analysis, NADPH titration and thioredoxin assays. · source_derived_draft · unverified_draft
### b2-txnrd-sec498cys-turnover Replacing rat TXNRD1 Sec498 with cysteine lowered thioredoxin-reduction kcat about 100-fold; serine substitution and terminal truncation lacked detectable activity. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Flavin retention did not preserve efficient thioredoxin reduction. organism: Rattus norvegicus protein expressed in Escherichia coli tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Rat TXNRD1 Sec498Cys, Sec498Ser and C-terminal truncation expressed in E. coli; FAD analysis, NADPH titration and thioredoxin assays. limitations: Assay-substrate species is unresolved in accessible source details; engineered proteins do not establish dietary B2-by-selenium synergy. exposure: Purified-enzyme assay cross_nutrient: B2-derived FAD cannot replace the selenium-containing catalytic residue. evidence_location: Abstract [zhong2000] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200
Complete structured claim and evidence
Brush-border membrane vesicles from riboflavin-deficient rats took up less iron than identically prepared control vesicles.
Riboflavin (vitamin B2) → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 deficiency impairs an iron-uptake process in this rat model.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.
exposure
Dietary riboflavin deficiency
limitations
No specific transporter or ferrireductase was identified; the result must not be assigned to DMT1, DCYTB or ferritin release without evidence.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
The deficiency affected iron entry at the intestinal surface.
primary_references
[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
tissue_or_cell_type
Intestinal brush-border membrane vesicles
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1402–1414
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft
### b2-rat-iron-brush-border-uptake Brush-border membrane vesicles from riboflavin-deficient rats took up less iron than identically prepared control vesicles. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The deficiency affected iron entry at the intestinal surface. organism: Rattus norvegicus tissue_or_cell_type: Intestinal brush-border membrane vesicles experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: No specific transporter or ferrireductase was identified; the result must not be assigned to DMT1, DCYTB or ferritin release without evidence. exposure: Dietary riboflavin deficiency cross_nutrient: B2 deficiency impairs an iron-uptake process in this rat model. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
Complete structured claim and evidence
Riboflavin-deficient rats transferred less intragastrically administered 59Fe to plasma than age- or weight-matched controls.
Riboflavin (vitamin B2) → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 status changed systemic appearance of administered iron.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.
exposure
Dietary riboflavin deficiency plus intragastric 59Fe
limitations
Rat tracer experiment; does not establish an identical human absorption response.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Less of the administered iron reached the blood.
primary_references
[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
tissue_or_cell_type
Intestine and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1416–1428
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft
### b2-rat-enteral-iron-transfer Riboflavin-deficient rats transferred less intragastrically administered 59Fe to plasma than age- or weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the administered iron reached the blood. organism: Rattus norvegicus tissue_or_cell_type: Intestine and plasma experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Rat tracer experiment; does not establish an identical human absorption response. exposure: Dietary riboflavin deficiency plus intragastric 59Fe cross_nutrient: B2 status changed systemic appearance of administered iron. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
Complete structured claim and evidence
Thirty minutes after iron dosing, riboflavin-deficient rats had less mucosal 59Fe but unchanged relative partition between ferritin and transferrin.
Riboflavin (vitamin B2) → Intestinal mucosal iron partition source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Constrains the proposed B2-iron mechanism.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.
exposure
Dietary riboflavin deficiency; 30-minute tracer endpoint
limitations
Only the reported pools and time point were compared.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
The uptake decrease was not explained by the tested redistribution hypothesis.
primary_references
[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
tissue_or_cell_type
Intestinal mucosa
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1430–1442
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft
### b2-rat-iron-partition-preserved Thirty minutes after iron dosing, riboflavin-deficient rats had less mucosal 59Fe but unchanged relative partition between ferritin and transferrin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The uptake decrease was not explained by the tested redistribution hypothesis. organism: Rattus norvegicus tissue_or_cell_type: Intestinal mucosa experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Only the reported pools and time point were compared. exposure: Dietary riboflavin deficiency; 30-minute tracer endpoint cross_nutrient: Constrains the proposed B2-iron mechanism. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
Complete structured claim and evidence
Riboflavin-deficient weanling rats showed approximately doubled crypt-cell production and deeper small-intestinal crypts versus controls.
Riboflavin (vitamin B2) → Intestinal crypt cell production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Altered B2-dependent intestinal maintenance may affect endogenous iron retention.
evidence_location
Abstract
experimental_model
Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing.
exposure
Dietary riboflavin deficiency
limitations
Association with iron loss does not prove that epithelial turnover alone caused it.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
The intestinal lining was renewed faster during deficiency.
primary_references
[powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055
tissue_or_cell_type
Upper and middle small intestine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1444–1456
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. · source_derived_draft · unverified_draft
### b2-rat-crypt-production Riboflavin-deficient weanling rats showed approximately doubled crypt-cell production and deeper small-intestinal crypts versus controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestinal lining was renewed faster during deficiency. organism: Rattus norvegicus tissue_or_cell_type: Upper and middle small intestine experimental_model: Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. limitations: Association with iron loss does not prove that epithelial turnover alone caused it. exposure: Dietary riboflavin deficiency cross_nutrient: Altered B2-dependent intestinal maintenance may affect endogenous iron retention. evidence_location: Abstract [powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055
Complete structured claim and evidence
After intraperitoneal 59Fe, riboflavin-deficient rats lost about twice as much endogenous tracer in feces as weight-matched controls.
Riboflavin (vitamin B2) → Endogenous fecal iron loss source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 status affected post-absorption iron retention in rats.
evidence_location
Abstract
experimental_model
Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing.
exposure
Dietary riboflavin deficiency plus intraperitoneal tracer
limitations
The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Deficiency increased loss of iron already inside the body.
primary_references
[powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055
tissue_or_cell_type
Gastrointestinal tract and feces
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1458–1470
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. · source_derived_draft · unverified_draft
### b2-rat-endogenous-iron-loss After intraperitoneal 59Fe, riboflavin-deficient rats lost about twice as much endogenous tracer in feces as weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deficiency increased loss of iron already inside the body. organism: Rattus norvegicus tissue_or_cell_type: Gastrointestinal tract and feces experimental_model: Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. limitations: The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron. exposure: Dietary riboflavin deficiency plus intraperitoneal tracer cross_nutrient: B2 status affected post-absorption iron retention in rats. evidence_location: Abstract [powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055
Complete structured claim and evidence
Added glutathione failed to protect hemoglobin during oxidant challenge of selenium-deficient rat hemolyzates with very low glutathione-peroxidase activity.
GSH → Hemoglobin oxidative damage source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements.
evidence_location
Abstract
experimental_model
Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification.
exposure
Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure
limitations
Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Supplying glutathione did not replace the missing selenium-dependent enzyme activity.
primary_references
[rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588
tissue_or_cell_type
Erythrocyte hemolyzates
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1472–1484
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. · source_derived_draft · unverified_draft
### b2-redox-gsh-needs-selenium-peroxidase Added glutathione failed to protect hemoglobin during oxidant challenge of selenium-deficient rat hemolyzates with very low glutathione-peroxidase activity. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying glutathione did not replace the missing selenium-dependent enzyme activity. organism: Rattus norvegicus tissue_or_cell_type: Erythrocyte hemolyzates experimental_model: Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. limitations: Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested. exposure: Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure cross_nutrient: Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements. evidence_location: Abstract [rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588
Complete structured claim and evidence
Riboflavin lowered plasma homocysteine in the MTHFR 677TT group by 22% overall; the lower-baseline-B2 subgroup showed a 40% decrease.
Riboflavin (vitamin B2) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B2 cofactor supply interacts with folate-cycle enzyme genotype.
experimental_model
Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65.
exposure
1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen.
genotype
MTHFR 677TT; common variant rather than complete loss of enzyme
limitations
Small genotype strata; subgroup magnitude is not an expected response for every TT carrier. The trial did not test cardiovascular events.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
In this trial, improving B2 supply lowered a folate-pathway blood marker in people with two copies of the studied MTHFR variant.
primary_references
[b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
tissue_or_cell_type
Human clinical setting
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1486–1498
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. · source_derived_draft · unverified_draft
### b2-tt-homocysteine-response Riboflavin lowered plasma homocysteine in the MTHFR 677TT group by 22% overall; the lower-baseline-B2 subgroup showed a 40% decrease. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this trial, improving B2 supply lowered a folate-pathway blood marker in people with two copies of the studied MTHFR variant. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. limitations: Small genotype strata; subgroup magnitude is not an expected response for every TT carrier. The trial did not test cardiovascular events. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen. cross_nutrient: B2 cofactor supply interacts with folate-cycle enzyme genotype. genotype: MTHFR 677TT; common variant rather than complete loss of enzyme [b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
Complete structured claim and evidence
No homocysteine response was observed in the CC or CT groups despite improved riboflavin-status measures in all genotype groups.
Riboflavin (vitamin B2) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate-cycle biomarker response was genotype dependent.
experimental_model
Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65.
exposure
1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen.
genotype
MTHFR 677CC or 677CT
limitations
Null findings in modest samples do not prove an effect is impossible; context differs from the TT arm.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A better B2 test result did not automatically lower homocysteine in everyone.
primary_references
[b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
tissue_or_cell_type
Human clinical setting
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1500–1512
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. · source_derived_draft · unverified_draft
### b2-cc-ct-homocysteine-nonresponse No homocysteine response was observed in the CC or CT groups despite improved riboflavin-status measures in all genotype groups. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A better B2 test result did not automatically lower homocysteine in everyone. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. limitations: Null findings in modest samples do not prove an effect is impossible; context differs from the TT arm. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen. cross_nutrient: Folate-cycle biomarker response was genotype dependent. genotype: MTHFR 677CC or 677CT [b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
Complete structured claim and evidence
In the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites.
Riboflavin (vitamin B2) → S-Adenosyl-L-methionine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers.
experimental_model
Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo.
exposure
1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial.
limitations
Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.
primary_references
[b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004
tissue_or_cell_type
Human clinical setting
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1514–1525
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo. · source_derived_draft · unverified_draft
### b2-tt-plasma-sam-response In the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo. limitations: Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP. exposure: 1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial. cross_nutrient: B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers. [b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004
Complete structured claim and evidence
In hypertensive adults with MTHFR 677TT, the systolic treatment effect was 5.6±2.6 mmHg favoring riboflavin; the diastolic effect was not significant.
Riboflavin (vitamin B2) → Arterial blood pressure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Gene-cofactor clinical interaction; mechanism mediation was not demonstrated.
experimental_model
91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment.
exposure
1.6 mg/day riboflavin versus placebo for 16 weeks; experimental regimen.
limitations
Selected TT population; no proof of universal BP benefit, event reduction or a specific NO/methylation mechanism. Null diastolic endpoint retained.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A genotype-targeted trial found a systolic blood-pressure benefit while participants continued their usual medicines.
primary_references
[b2-wilson2013] Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial (2013). https://pubmed.ncbi.nlm.nih.gov/23608654/ DOI: 10.1161/hypertensionaha.111.01047
tissue_or_cell_type
Human clinical setting
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1527–1538
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment. · source_derived_draft · unverified_draft
### b2-tt-bp-trial In hypertensive adults with MTHFR 677TT, the systolic treatment effect was 5.6±2.6 mmHg favoring riboflavin; the diastolic effect was not significant. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A genotype-targeted trial found a systolic blood-pressure benefit while participants continued their usual medicines. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment. limitations: Selected TT population; no proof of universal BP benefit, event reduction or a specific NO/methylation mechanism. Null diastolic endpoint retained. exposure: 1.6 mg/day riboflavin versus placebo for 16 weeks; experimental regimen. cross_nutrient: Gene-cofactor clinical interaction; mechanism mediation was not demonstrated. [b2-wilson2013] Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial (2013). https://pubmed.ncbi.nlm.nih.gov/23608654/ DOI: 10.1161/hypertensionaha.111.01047
Complete structured claim and evidence
A four-year follow-up with reversed intervention assignments in 31 TT participants again reported BP lowering during riboflavin administration.
Riboflavin (vitamin B2) → Arterial blood pressure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed.
exposure
1.6 mg/day for 16 weeks in 2004 and again in 2008 with reversed allocations; not four years of continuous supplementation.
limitations
Follow-up selection, small TT sample and changing antihypertensive treatment limit inference; overlaps earlier cohort.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The earlier participants were studied again; this supports repeat responsiveness but is not an independent population or continuous four-year treatment.
primary_references
[b2-wilson2012] Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up (2012). https://pubmed.ncbi.nlm.nih.gov/22277556/ DOI: 10.3945/ajcn.111.026245
tissue_or_cell_type
Human clinical setting
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1540–1550
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed. · source_derived_draft · unverified_draft
### b2-tt-bp-rechallenge A four-year follow-up with reversed intervention assignments in 31 TT participants again reported BP lowering during riboflavin administration. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The earlier participants were studied again; this supports repeat responsiveness but is not an independent population or continuous four-year treatment. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed. limitations: Follow-up selection, small TT sample and changing antihypertensive treatment limit inference; overlaps earlier cohort. exposure: 1.6 mg/day for 16 weeks in 2004 and again in 2008 with reversed allocations; not four years of continuous supplementation. [b2-wilson2012] Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up (2012). https://pubmed.ncbi.nlm.nih.gov/22277556/ DOI: 10.3945/ajcn.111.026245
Complete structured claim and evidence
In RIBOFEM, improvement in B2 status correlated with hemoglobin increase among supplemented women; women with baseline EGRAC >1.65 had the greater hemoglobin response.
Riboflavin (vitamin B2) → Blood hemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Riboflavin status modifies iron-related hematologic outcomes.
experimental_model
RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34.
exposure
Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens.
limitations
Baseline-tertile and response associations should not be restated as a uniform hemoglobin benefit in every randomized participant.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Women with poorer starting B2 status tended to gain more hemoglobin when their B2 status improved.
primary_references
[b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1552–1563
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. · source_derived_draft · unverified_draft
### b2-ribofem-hemoglobin In RIBOFEM, improvement in B2 status correlated with hemoglobin increase among supplemented women; women with baseline EGRAC >1.65 had the greater hemoglobin response. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Women with poorer starting B2 status tended to gain more hemoglobin when their B2 status improved. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. limitations: Baseline-tertile and response associations should not be restated as a uniform hemoglobin benefit in every randomized participant. exposure: Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens. cross_nutrient: Riboflavin status modifies iron-related hematologic outcomes. [b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409
Complete structured claim and evidence
RIBOFEM found no change in dietary iron intake or measured iron absorption during the riboflavin intervention.
Riboflavin (vitamin B2) → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Iron absorption and iron use remain separate entities.
experimental_model
RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34.
exposure
Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens.
limitations
Small absorption subgroup; no measured change is not proof of identical absorption in all settings. Actual downstream causal step remains unresolved.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The blood response could not simply be explained by absorbing more iron in the measured subgroup.
primary_references
[b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1565–1576
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. · source_derived_draft · unverified_draft
### b2-ribofem-absorption RIBOFEM found no change in dietary iron intake or measured iron absorption during the riboflavin intervention. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood response could not simply be explained by absorbing more iron in the measured subgroup. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. limitations: Small absorption subgroup; no measured change is not proof of identical absorption in all settings. Actual downstream causal step remains unresolved. exposure: Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens. cross_nutrient: Iron absorption and iron use remain separate entities. [b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409
Complete structured claim and evidence
Riboflavin supplementation improved B2 status and hemoglobin in deficient Gambian men; low plasma ferritin did not change.
Riboflavin (vitamin B2) → Blood hemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 and iron supply can constrain different parts of erythropoiesis.
experimental_model
Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.
exposure
Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.
limitations
Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Hemoglobin improved even though the measured storage marker stayed low.
primary_references
[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1578–1589
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft
### b2-gambia-hemoglobin Riboflavin supplementation improved B2 status and hemoglobin in deficient Gambian men; low plasma ferritin did not change. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hemoglobin improved even though the measured storage marker stayed low. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: B2 and iron supply can constrain different parts of erythropoiesis. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
Complete structured claim and evidence
Stable-isotope iron absorption varied widely within and between Gambian participants and showed no measurable change after riboflavin.
Riboflavin (vitamin B2) → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Iron-use improvement is distinct from intestinal absorption.
experimental_model
Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.
exposure
Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.
limitations
Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This human study does not support a blanket claim that B2 always raises iron absorption.
primary_references
[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1591–1602
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft
### b2-gambia-iron-absorption Stable-isotope iron absorption varied widely within and between Gambian participants and showed no measurable change after riboflavin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This human study does not support a blanket claim that B2 always raises iron absorption. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: Iron-use improvement is distinct from intestinal absorption. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
Complete structured claim and evidence
Adding retinol and/or riboflavin to iron-folic-acid treatment reduced anemia prevalence more than iron-folic-acid alone; the combined retinol-riboflavin arm gained 5.4±1.1 g/L more hemoglobin than the reference arm.
Riboflavin (vitamin B2) → Blood hemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct clinical comparison involving B2, vitamin A, iron and folic acid.
experimental_model
366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid.
exposure
All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations.
limitations
Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone.
primary_references
[b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946
tissue_or_cell_type
Human clinical setting
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1604–1615
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. · source_derived_draft · unverified_draft
### b2-pregnancy-multiple-nutrients Adding retinol and/or riboflavin to iron-folic-acid treatment reduced anemia prevalence more than iron-folic-acid alone; the combined retinol-riboflavin arm gained 5.4±1.1 g/L more hemoglobin than the reference arm. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. limitations: Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint. exposure: All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations. cross_nutrient: Direct clinical comparison involving B2, vitamin A, iron and folic acid. [b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946
Complete structured claim and evidence
In 46 randomized older adults, supplementation increased plasma riboflavin by 83% and erythrocyte FMN by 87%; measured markers other than plasma FAD responded significantly.
Riboflavin (vitamin B2) → Plasma riboflavin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo.
exposure
1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements.
limitations
Older adults selected by EGRAC; percentages are study responses, not diagnostic thresholds or predicted individual gains.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Blood B2 comes in several forms, and they do not all respond equally to intake.
primary_references
[b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1617–1627
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. · source_derived_draft · unverified_draft
### b2-blood-vitamer-response In 46 randomized older adults, supplementation increased plasma riboflavin by 83% and erythrocyte FMN by 87%; measured markers other than plasma FAD responded significantly. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood B2 comes in several forms, and they do not all respond equally to intake. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. limitations: Older adults selected by EGRAC; percentages are study responses, not diagnostic thresholds or predicted individual gains. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements. [b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571
Complete structured claim and evidence
Plasma FAD did not respond significantly to supplementation in the older-adult trial although plasma riboflavin, erythrocyte FMN and other measures did.
Riboflavin (vitamin B2) → Plasma FAD concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo.
exposure
1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements.
limitations
A result in this population does not invalidate every use of plasma FAD; cellular compartment and clinical state matter.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A stable plasma FAD reading did not mean that all B2-related pools were unchanged.
primary_references
[b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1629–1639
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. · source_derived_draft · unverified_draft
### b2-plasma-fad-nonresponse Plasma FAD did not respond significantly to supplementation in the older-adult trial although plasma riboflavin, erythrocyte FMN and other measures did. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stable plasma FAD reading did not mean that all B2-related pools were unchanged. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. limitations: A result in this population does not invalidate every use of plasma FAD; cellular compartment and clinical state matter. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements. [b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571
Complete structured claim and evidence
Critically ill patients had higher plasma riboflavin and FMN but lower plasma and red-cell FAD than healthy controls; plasma-vitamer relationships were disrupted.
Plasma riboflavin concentration → Erythrocyte FAD concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
119 healthy controls and 125 critically ill patients at admission; repeat measurements in 60 patients.
exposure
Observational HPLC plasma and red-cell riboflavin, FMN andFAD; no isolated treatment.
limitations
Observational illness comparison cannot diagnose tissue deficiency or establish that supplementation improves outcomes.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A high circulating B2 concentration during critical illness can coexist with a lower measured cellular FAD pool.
primary_references
[b2-ventura2010] Relation between riboflavin, flavin mononucleotide and flavin adenine dinucleotide concentrations in plasma and red cells in patients with critical illness (2010). https://pubmed.ncbi.nlm.nih.gov/20667447/ DOI: 10.1016/j.cca.2010.07.024
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1641–1651
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 119 healthy controls and 125 critically ill patients at admission; repeat measurements in 60 patients. · source_derived_draft · unverified_draft
### b2-critical-illness-pools Critically ill patients had higher plasma riboflavin and FMN but lower plasma and red-cell FAD than healthy controls; plasma-vitamer relationships were disrupted. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high circulating B2 concentration during critical illness can coexist with a lower measured cellular FAD pool. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 119 healthy controls and 125 critically ill patients at admission; repeat measurements in 60 patients. limitations: Observational illness comparison cannot diagnose tissue deficiency or establish that supplementation improves outcomes. exposure: Observational HPLC plasma and red-cell riboflavin, FMN andFAD; no isolated treatment. [b2-ventura2010] Relation between riboflavin, flavin mononucleotide and flavin adenine dinucleotide concentrations in plasma and red cells in patients with critical illness (2010). https://pubmed.ncbi.nlm.nih.gov/20667447/ DOI: 10.1016/j.cca.2010.07.024
Complete structured claim and evidence
Erythrocyte PPO activity and its activation coefficient responded to B2 supplementation and correlated with EGRAC; enzyme activity showed a dose response.
Riboflavin (vitamin B2) → Erythrocyte pyridoxamine/pyridoxine phosphate oxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
A B6-activation enzyme provides a B2-sensitive functional assay.
experimental_model
Assay-development study using hemolysates from the RIBOFEM riboflavin intervention; same trial registration ISRCTN35811298.
exposure
Erythrocyte PPO activity with/without flavin activation; 2 and 4 mg/day supplementation arms. Not independent replication of RIBOFEM.
limitations
Assay-development analysis shares samples with RIBOFEM; not independent replication. Proposed utility in G6PD deficiency requires population-specific validation.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
An enzyme used to activate B6 can also reveal aspects of B2 status because it needs an FMN cofactor.
primary_references
[b2-mushtaq2009] Erythrocyte pyridoxamine phosphate oxidase activity: a potential biomarker of riboflavin status? (2009). https://pubmed.ncbi.nlm.nih.gov/19740970/ DOI: 10.3945/ajcn.2009.28338
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1653–1664
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Assay-development study using hemolysates from the RIBOFEM riboflavin intervention; same trial registration ISRCTN35811298. · source_derived_draft · unverified_draft
### b2-ppo-biomarker-response Erythrocyte PPO activity and its activation coefficient responded to B2 supplementation and correlated with EGRAC; enzyme activity showed a dose response. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme used to activate B6 can also reveal aspects of B2 status because it needs an FMN cofactor. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Assay-development study using hemolysates from the RIBOFEM riboflavin intervention; same trial registration ISRCTN35811298. limitations: Assay-development analysis shares samples with RIBOFEM; not independent replication. Proposed utility in G6PD deficiency requires population-specific validation. exposure: Erythrocyte PPO activity with/without flavin activation; 2 and 4 mg/day supplementation arms. Not independent replication of RIBOFEM. cross_nutrient: A B6-activation enzyme provides a B2-sensitive functional assay. [b2-mushtaq2009] Erythrocyte pyridoxamine phosphate oxidase activity: a potential biomarker of riboflavin status? (2009). https://pubmed.ncbi.nlm.nih.gov/19740970/ DOI: 10.3945/ajcn.2009.28338
Complete structured claim and evidence
In G6PD-deficient erythrocytes, glutathione reductase was usually already FAD-saturated despite evidence of low FMN-dependent oxidase activity.
Glucose-6-phosphate dehydrogenase / G6PD → Erythrocyte glutathione reductase activation coefficient / EGRAC source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
G6PD genotype and distinct flavin pools alter interpretation of B2/B6-linked assays.
experimental_model
Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls.
exposure
In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations.
limitations
Human red-cell observation; the proposed faster FMN-to-FAD flux was an interpretation, not a directly measured universal mechanism.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A red-cell FAD saturation test can look adequate while another B2-dependent enzyme system is poorly supplied.
primary_references
[b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1666–1677
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. · source_derived_draft · unverified_draft
### b2-g6pd-fad-assay-limit In G6PD-deficient erythrocytes, glutathione reductase was usually already FAD-saturated despite evidence of low FMN-dependent oxidase activity. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A red-cell FAD saturation test can look adequate while another B2-dependent enzyme system is poorly supplied. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. limitations: Human red-cell observation; the proposed faster FMN-to-FAD flux was an interpretation, not a directly measured universal mechanism. exposure: In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations. cross_nutrient: G6PD genotype and distinct flavin pools alter interpretation of B2/B6-linked assays. [b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x
Complete structured claim and evidence
Low FMN-dependent PNP oxidase activity in many G6PD-deficient participants responded to oral riboflavin despite the contrasting FAD-saturated GSR pattern.
Riboflavin (vitamin B2) → Erythrocyte pyridoxamine/pyridoxine phosphate oxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
B2 cofactor supply affects a B6-activation assay.
experimental_model
Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls.
exposure
In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations.
limitations
No isolated whole-body B6 flux or clinical seizure/neuropathy outcome was established.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
FMN and FAD should not be treated as one interchangeable vitamin pool.
primary_references
[b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1679–1690
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. · source_derived_draft · unverified_draft
### b2-g6pd-fmn-oxidase-response Low FMN-dependent PNP oxidase activity in many G6PD-deficient participants responded to oral riboflavin despite the contrasting FAD-saturated GSR pattern. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FMN and FAD should not be treated as one interchangeable vitamin pool. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. limitations: No isolated whole-body B6 flux or clinical seizure/neuropathy outcome was established. exposure: In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations. cross_nutrient: B2 cofactor supply affects a B6-activation assay. [b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x
Complete structured claim and evidence
Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison.
Riboflavin (vitamin B2) → Erythrocyte glutathione reductase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion.
experimental_model
Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.
exposure
Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.
limitations
Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A B2-dependent recycling enzyme was less active in red cells from the deficient group.
primary_references
[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1692–1703
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft
### b2-deficiency-redcell-gsr Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B2-dependent recycling enzyme was less active in red cells from the deficient group. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. cross_nutrient: B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
Complete structured claim and evidence
Methemoglobin was higher in erythrocytes from the marginally B2-deficient group; the other tested endpoints did not all differ from controls.
Riboflavin (vitamin B2) → Erythrocyte methemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.
exposure
Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.
limitations
Does not identify a single responsible reductase or prove clinically significant anemia/hemolysis in each person.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The study found a specific hemoglobin oxidation change, not failure of every antioxidant measure.
primary_references
[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1705–1715
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft
### b2-deficiency-methemoglobin Methemoglobin was higher in erythrocytes from the marginally B2-deficient group; the other tested endpoints did not all differ from controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study found a specific hemoglobin oxidation change, not failure of every antioxidant measure. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Does not identify a single responsible reductase or prove clinically significant anemia/hemolysis in each person. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
Complete structured claim and evidence
A55-person adult migraine trial found lower attack frequency and headache days with riboflavin than placebo.
Riboflavin (vitamin B2) → Migraine attack frequency source_derived_draftungraded
Experimental context and source evidence
experimental_model
Double-blind placebo-controlled trial in 55 migraine patients; intention-to-treat analysis.
exposure
400 mg/day riboflavin or placebo for three months; pharmacological exposure.
limitations
Pharmacological dose, small sample and no direct mitochondrial mechanism measurement; prevention rather than acute pain relief.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A small adult trial found preventive benefit; it did not establish that migraine is a B2-deficiency disease.
primary_references
[b2-schoenen1998] Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial (1998). https://pubmed.ncbi.nlm.nih.gov/9484373/ DOI: 10.1212/wnl.50.2.466
tissue_or_cell_type
Adults with migraine
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1717–1727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled trial in 55 migraine patients; intention-to-treat analysis. · source_derived_draft · unverified_draft
### b2-migraine-adult-trial A55-person adult migraine trial found lower attack frequency and headache days with riboflavin than placebo. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small adult trial found preventive benefit; it did not establish that migraine is a B2-deficiency disease. organism: Homo sapiens tissue_or_cell_type: Adults with migraine experimental_model: Double-blind placebo-controlled trial in 55 migraine patients; intention-to-treat analysis. limitations: Pharmacological dose, small sample and no direct mitochondrial mechanism measurement; prevention rather than acute pain relief. exposure: 400 mg/day riboflavin or placebo for three months; pharmacological exposure. [b2-schoenen1998] Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial (1998). https://pubmed.ncbi.nlm.nih.gov/9484373/ DOI: 10.1212/wnl.50.2.466
Complete structured claim and evidence
In the 48-child trial,>=50% attack reduction occurred in 12/27 riboflavin versus 14/21 placebo participants; no primary or secondary endpoint differed significantly.
Riboflavin (vitamin B2) → Migraine attack frequency source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized double-blind placebo-controlled trial in 48 children with migraine.
exposure
200 mg/day riboflavin versus placebo; primary endpoint>=50% reduction in attack frequency; pharmacological exposure.
limitations
High placebo response and modest sample; null evidence does not prove impossibility of benefit in every child.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
One pediatric trial found no preventive advantage over placebo.
primary_references
[b2-maclennan2008] High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial (2008). https://pubmed.ncbi.nlm.nih.gov/18984840/ DOI: 10.1177/0883073808318053
tissue_or_cell_type
Children with migraine
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1729–1739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial in 48 children with migraine. · source_derived_draft · unverified_draft
### b2-migraine-child-null In the 48-child trial,>=50% attack reduction occurred in 12/27 riboflavin versus 14/21 placebo participants; no primary or secondary endpoint differed significantly. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One pediatric trial found no preventive advantage over placebo. organism: Homo sapiens tissue_or_cell_type: Children with migraine experimental_model: Randomized double-blind placebo-controlled trial in 48 children with migraine. limitations: High placebo response and modest sample; null evidence does not prove impossibility of benefit in every child. exposure: 200 mg/day riboflavin versus placebo; primary endpoint>=50% reduction in attack frequency; pharmacological exposure. [b2-maclennan2008] High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial (2008). https://pubmed.ncbi.nlm.nih.gov/18984840/ DOI: 10.1177/0883073808318053
Complete structured claim and evidence
In the 90-child three-arm study,>=50% frequency reduction occurred in 24/30 on 200 mg/day versus 4/30 placebo; 100 mg/day did not show a significant benefit.
Riboflavin (vitamin B2) → Migraine attack frequency source_derived_draftungraded
Experimental context and source evidence
experimental_model
90 children ages 5-13 randomized equally to placebo, 100 mg or 200 mg riboflavin; 12-week trial.
exposure
100 or 200 mg/day riboflavin versus placebo; missing follow-up values carried forward from baseline; pharmacological exposure.
limitations
Single-center study, small arms and baseline values carried forward for missing follow-up; genotype and deficiency did not establish the reason for discordance.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A later pediatric trial reported benefit at the same 200 mg daily exposure used in the earlier negative study.
primary_references
[b2-talebian2018] Prophylactic effect of riboflavin on pediatric migraine: a randomized, double-blind, placebo-controlled trial (2018). https://pubmed.ncbi.nlm.nih.gov/29629048/ DOI: 10.19082/6279
tissue_or_cell_type
Children with migraine
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1741–1751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 90 children ages 5-13 randomized equally to placebo, 100 mg or 200 mg riboflavin; 12-week trial. · source_derived_draft · unverified_draft
### b2-migraine-child-positive In the 90-child three-arm study,>=50% frequency reduction occurred in 24/30 on 200 mg/day versus 4/30 placebo; 100 mg/day did not show a significant benefit. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later pediatric trial reported benefit at the same 200 mg daily exposure used in the earlier negative study. organism: Homo sapiens tissue_or_cell_type: Children with migraine experimental_model: 90 children ages 5-13 randomized equally to placebo, 100 mg or 200 mg riboflavin; 12-week trial. limitations: Single-center study, small arms and baseline values carried forward for missing follow-up; genotype and deficiency did not establish the reason for discordance. exposure: 100 or 200 mg/day riboflavin versus placebo; missing follow-up values carried forward from baseline; pharmacological exposure. [b2-talebian2018] Prophylactic effect of riboflavin on pediatric migraine: a randomized, double-blind, placebo-controlled trial (2018). https://pubmed.ncbi.nlm.nih.gov/29629048/ DOI: 10.19082/6279
Complete structured claim and evidence
The 42-child crossover trial found no significant migraine-frequency reduction with 50 mg/day riboflavin; tension-type phenotype headaches showed a separate positive signal.
Riboflavin (vitamin B2) → Migraine attack frequency source_derived_draftungraded
Experimental context and source evidence
experimental_model
42 children ages 6-13 in randomized crossover trial; 14 also had tension-type headache.
exposure
50 mg/day riboflavin and placebo for 16 weeks each with four-week washout; pharmacological exposure.
limitations
Different dose from 200 mg trials, overlapping headache phenotypes and small sample; contextual result rather than a direct dose-matched contradiction.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The type of headache and study exposure matter; a signal for a different headache endpoint is not proof of migraine prevention.
primary_references
[b2-bruijn2010] Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial (2010). https://pubmed.ncbi.nlm.nih.gov/20974610/ DOI: 10.1177/0333102410365106
tissue_or_cell_type
Children with migraine and some interval tension-type headache
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1753–1763
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 42 children ages 6-13 in randomized crossover trial; 14 also had tension-type headache. · source_derived_draft · unverified_draft
### b2-migraine-lowdose-crossover The 42-child crossover trial found no significant migraine-frequency reduction with 50 mg/day riboflavin; tension-type phenotype headaches showed a separate positive signal. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The type of headache and study exposure matter; a signal for a different headache endpoint is not proof of migraine prevention. organism: Homo sapiens tissue_or_cell_type: Children with migraine and some interval tension-type headache experimental_model: 42 children ages 6-13 in randomized crossover trial; 14 also had tension-type headache. limitations: Different dose from 200 mg trials, overlapping headache phenotypes and small sample; contextual result rather than a direct dose-matched contradiction. exposure: 50 mg/day riboflavin and placebo for 16 weeks each with four-week washout; pharmacological exposure. [b2-bruijn2010] Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial (2010). https://pubmed.ncbi.nlm.nih.gov/20974610/ DOI: 10.1177/0333102410365106
Complete structured claim and evidence
Maternal supplementation increased breast-milk riboflavin and improved maternal status compared with placebo in the Gambian lactation trial.
Riboflavin (vitamin B2) → Human milk riboflavin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants.
exposure
Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations.
limitations
Nutritionally constrained population; no direct mammary transporter assay in this trial.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The mother’s B2 supply affected the vitamin delivered in milk.
primary_references
[b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701
tissue_or_cell_type
Maternal blood and human milk
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1765–1775
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. · source_derived_draft · unverified_draft
### b2-maternal-milk-response Maternal supplementation increased breast-milk riboflavin and improved maternal status compared with placebo in the Gambian lactation trial. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mother’s B2 supply affected the vitamin delivered in milk. organism: Homo sapiens tissue_or_cell_type: Maternal blood and human milk experimental_model: Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. limitations: Nutritionally constrained population; no direct mammary transporter assay in this trial. exposure: Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations. [b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701
Complete structured claim and evidence
Infants of supplemented mothers had lower activation coefficients; maternal and infant values rose toward placebo levels after supplement withdrawal.
Human milk riboflavin concentration → Erythrocyte glutathione reductase activation coefficient / EGRAC source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants.
exposure
Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations.
limitations
Supports maternal-infant supply responsiveness; not proof of a developmental benefit or an independently measured transport mechanism.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The infant marker improved while maternal B2 was supplied and worsened again after it stopped.
primary_references
[b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701
tissue_or_cell_type
Infant erythrocytes in maternal lactation trial
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1777–1787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. · source_derived_draft · unverified_draft
### b2-milk-infant-marker-response Infants of supplemented mothers had lower activation coefficients; maternal and infant values rose toward placebo levels after supplement withdrawal. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The infant marker improved while maternal B2 was supplied and worsened again after it stopped. organism: Homo sapiens tissue_or_cell_type: Infant erythrocytes in maternal lactation trial experimental_model: Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. limitations: Supports maternal-infant supply responsiveness; not proof of a developmental benefit or an independently measured transport mechanism. exposure: Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations. [b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701
Complete structured claim and evidence
All six patients developed cheilosis and angular stomatitis during combined restriction/galactoflavin exposure; five developed glossitis and all developed dermatitis.
Riboflavin (vitamin B2) → Mucocutaneous lesions during riboflavin deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.
exposure
Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.
limitations
Advanced cancer, antagonist exposure and antibiotic use in three patients; lesions are not diagnostic of B2 deficiency by appearance alone.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Severely reduced usable B2 affected lips, mouth and skin in this historical experiment.
primary_references
[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
tissue_or_cell_type
Oral mucosa, lips and skin
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1789–1799
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft
### b2-induced-mouth-skin-lesions All six patients developed cheilosis and angular stomatitis during combined restriction/galactoflavin exposure; five developed glossitis and all developed dermatitis. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severely reduced usable B2 affected lips, mouth and skin in this historical experiment. organism: Homo sapiens tissue_or_cell_type: Oral mucosa, lips and skin experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Advanced cancer, antagonist exposure and antibiotic use in three patients; lesions are not diagnostic of B2 deficiency by appearance alone. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
Complete structured claim and evidence
All six patients developed anemia; the study described low reticulocytes and erythroid suppression with recovery during riboflavin replacement.
Riboflavin (vitamin B2) → Erythroid cell production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Iron supply alone did not prevent anemia in the combined B2 restriction/antagonist experiment.
experimental_model
Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.
exposure
Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.
limitations
Same six-patient experiment as lesion record; other nutrients were supplied but cancer and antagonist effects limit causal generalization.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Severe induced shortage reduced new red-cell production; the anemia was not simply assumed to be low dietary iron.
primary_references
[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
tissue_or_cell_type
Bone marrow and circulating erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1801–1812
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft
### b2-induced-erythroid-suppression All six patients developed anemia; the study described low reticulocytes and erythroid suppression with recovery during riboflavin replacement. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe induced shortage reduced new red-cell production; the anemia was not simply assumed to be low dietary iron. organism: Homo sapiens tissue_or_cell_type: Bone marrow and circulating erythrocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Same six-patient experiment as lesion record; other nutrients were supplied but cancer and antagonist effects limit causal generalization. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Iron supply alone did not prevent anemia in the combined B2 restriction/antagonist experiment. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
Complete structured claim and evidence
In two patients with induced B2 deficiency, parenteral iron did not trigger reticulocytosis, whereas subsequent riboflavin did.
Iron → Erythroid cell production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Documented failure of iron response in a specific induced B2-deficiency setting.
experimental_model
Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.
exposure
Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.
limitations
Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
More iron did not restore new red-cell production while usable B2 was severely limited in these cases.
primary_references
[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
tissue_or_cell_type
Circulating reticulocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1814–1825
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft
### b2-induced-iron-response-failure In two patients with induced B2 deficiency, parenteral iron did not trigger reticulocytosis, whereas subsequent riboflavin did. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iron did not restore new red-cell production while usable B2 was severely limited in these cases. organism: Homo sapiens tissue_or_cell_type: Circulating reticulocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Documented failure of iron response in a specific induced B2-deficiency setting. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
Complete structured claim and evidence
Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP.
Human kynureninase / KYNU → 3-Hydroxy-L-kynurenine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP-dependent KYNU follows the FAD-dependent KMO step, connecting B6 and B2 with tryptophan-niacin metabolism.
existing_related_claim_ids
["5570a502-6ebf-5397-bf2a-0148727e7695"]
experimental_model
Recombinant human KYNU crystallography and biochemical characterization
limitations
KYNU does not directly make NAD; subsequent enzymes and dietary niacin also contribute.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This B6-dependent step processes the product of upstream KMO chemistry.
primary_references
[b6-kynu-2007] Crystal Structure of Homo Sapiens Kynureninase (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC2531291/ DOI: 10.1021/bi0616697
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 885–896
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human KYNU crystallography and biochemical characterization · source_derived_draft · unverified_draft
### b6-met-kynu-hydrolysis Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step processes the product of upstream KMO chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human KYNU crystallography and biochemical characterization limitations: KYNU does not directly make NAD; subsequent enzymes and dietary niacin also contribute. cross_nutrient: PLP-dependent KYNU follows the FAD-dependent KMO step, connecting B6 and B2 with tryptophan-niacin metabolism. existing_related_claim_ids: ["5570a502-6ebf-5397-bf2a-0148727e7695"] [b6-kynu-2007] Crystal Structure of Homo Sapiens Kynureninase (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC2531291/ DOI: 10.1021/bi0616697
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
POR carries a FAD cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 407–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fad Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FAD cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
POR carries a FMN cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 422–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fmn Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FMN cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.
NADPH-cytochrome P450 oxidoreductase / POR → Human vitamin D 25-hydroxylase / CYP2R1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Figure 2C; Methods 2.3 and reconstitution assays.
experimental_model
Purified enzyme and phospholipid-vesicle reconstitution
exposure
0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C.
limitations
Assay optimum is not a tissue expression target or a vitamin dosing requirement.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens proteins
plain_language
CYP2R1 needs an electron-supplying partner.
primary_references
[cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
tissue_or_cell_type
reconstituted membrane
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 392–405
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme and phospholipid-vesicle reconstitution · source_derived_draft · unverified_draft
### vd-act-por-support Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2R1 needs an electron-supplying partner. organism: Homo sapiens proteins tissue_or_cell_type: reconstituted membrane experimental_model: Purified enzyme and phospholipid-vesicle reconstitution limitations: Assay optimum is not a tissue expression target or a vitamin dosing requirement. exposure: 0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C. cross_nutrient: true evidence_location: Primary Figure 2C; Methods 2.3 and reconstitution assays. nutrient: Vitamin D2 and D3 [cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
Complete structured claim and evidence
Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.
DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
evidence
[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLD crystallography with NAD+ and NADH.
limitations
Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
primary_references
[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft
### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
Complete structured claim and evidence
Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay.
2-Oxoglutarate dehydrogenase complex → Succinyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.
evidence
[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human multienzyme assay.
limitations
NADH assay measures overall complex turnover, not every intermediate independently.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.
primary_references
[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
tissue_or_cell_type
Purified enzyme complex
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human multienzyme assay. · source_derived_draft · unverified_draft
### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
Complete structured claim and evidence
Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study.
Zinc → Extracellular B-vitamin phosphate-ester hydrolysis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets
exposure
Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract.
limitations
Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Cell species not specified in abstract
plain_language
Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins.
primary_references
[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
tissue_or_cell_type
Cultured-cell membrane lysates
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 833–844
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft
### zinc-enz-bvitamin-cell-hydrolysis Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins. organism: Cell species not specified in abstract tissue_or_cell_type: Cultured-cell membrane lysates experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. exposure: Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
Complete structured claim and evidence
Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study.
Zinc → Extracellular B-vitamin phosphate-ester hydrolysis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets
exposure
Rats fed zinc-deficient diets; dietary content and duration not available in the abstract.
limitations
Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
Dietary zinc deficiency also reduced this measured enzyme activity in rat serum.
primary_references
[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
tissue_or_cell_type
Rat serum assayed ex vivo
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 846–857
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft
### zinc-enz-bvitamin-rat-hydrolysis Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary zinc deficiency also reduced this measured enzyme activity in rat serum. organism: Rattus norvegicus tissue_or_cell_type: Rat serum assayed ex vivo experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported. exposure: Rats fed zinc-deficient diets; dietary content and duration not available in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
Complete structured claim and evidence
Human MMACHC residues 1–244 supported cyanocobalamin decyanation with FMN or FAD plus NADPH, without a separately supplied flavoprotein reductase; reduced FMN also supported the reaction.
Human MMACHC deltaC38 → Cyanocobalamin source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Experimental procedures and Results: CblC Has a Flavin Reductase Fold; Figure 1c
experimental_model
Recombinant human MMACHC deltaC38 biochemical assay
exposure
30–40 micromolar FMN/FAD with 200 micromolar NADPH, or photoreduced FMN
limitations
Engineered truncation and reconstitution; does not establish that riboflavin supplementation rescues MMACHC defects.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
A truncated B12-processing protein could use supplied flavins to carry out this reaction.
primary_references
[koutmos-2011-flavin] Structural Basis of Multifunctionality in a Vitamin B12-processing Enzyme (2011). https://pubmed.ncbi.nlm.nih.gov/21697092/ DOI: 10.1074/jbc.M111.261370
tissue_or_cell_type
Cell-free assay
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 753–765
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MMACHC deltaC38 biochemical assay · source_derived_draft · unverified_draft
### b12-mmachc-free-flavin-decyanation Human MMACHC residues 1–244 supported cyanocobalamin decyanation with FMN or FAD plus NADPH, without a separately supplied flavoprotein reductase; reduced FMN also supported the reaction. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A truncated B12-processing protein could use supplied flavins to carry out this reaction. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Recombinant human MMACHC deltaC38 biochemical assay limitations: Engineered truncation and reconstitution; does not establish that riboflavin supplementation rescues MMACHC defects. exposure: 30–40 micromolar FMN/FAD with 200 micromolar NADPH, or photoreduced FMN cross_nutrient: true evidence_location: Experimental procedures and Results: CblC Has a Flavin Reductase Fold; Figure 1c [koutmos-2011-flavin] Structural Basis of Multifunctionality in a Vitamin B12-processing Enzyme (2011). https://pubmed.ncbi.nlm.nih.gov/21697092/ DOI: 10.1074/jbc.M111.261370
Complete structured claim and evidence
Recombinant human MTRR with NADPH supported MMACHC-bound cyanocobalamin conversion to cob(II)alamin; free cyanocobalamin was not detectably reduced without MMACHC.
Methionine synthase reductase / MTRR → Human MMACHC / cobalamin-processing protein CblC source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Results: Figure 4; Materials and Methods: Decyanation of CNCbl
experimental_model
Human purified-protein anaerobic reconstitution
exposure
4 micromolar reductase, 20 micromolar MMACHC/CNCbl, 200 micromolar NADPH
limitations
Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
This flavoprotein can pass reducing power into B12 processing.
primary_references
[kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 683–695
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human purified-protein anaerobic reconstitution · source_derived_draft · unverified_draft
### b12-mtrr-mmachc-electrons Recombinant human MTRR with NADPH supported MMACHC-bound cyanocobalamin conversion to cob(II)alamin; free cyanocobalamin was not detectably reduced without MMACHC. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This flavoprotein can pass reducing power into B12 processing. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Human purified-protein anaerobic reconstitution limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: 4 micromolar reductase, 20 micromolar MMACHC/CNCbl, 200 micromolar NADPH cross_nutrient: true evidence_location: Results: Figure 4; Materials and Methods: Decyanation of CNCbl [kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
Complete structured claim and evidence
Recombinant human NDOR1/NR1 with NADPH supported MMACHC-bound cyanocobalamin conversion to cob(II)alamin; free cyanocobalamin was not detectably reduced without MMACHC.
Human NADPH-dependent diflavin oxidoreductase 1 → Human MMACHC / cobalamin-processing protein CblC source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Results: Figure 4; Materials and Methods: Decyanation of CNCbl
experimental_model
Human purified-protein anaerobic reconstitution
exposure
4 micromolar reductase, 20 micromolar MMACHC/CNCbl, 200 micromolar NADPH
limitations
Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
This flavoprotein can pass reducing power into B12 processing.
primary_references
[kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 697–709
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human purified-protein anaerobic reconstitution · source_derived_draft · unverified_draft
### b12-ndor1-mmachc-electrons Recombinant human NDOR1/NR1 with NADPH supported MMACHC-bound cyanocobalamin conversion to cob(II)alamin; free cyanocobalamin was not detectably reduced without MMACHC. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This flavoprotein can pass reducing power into B12 processing. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Human purified-protein anaerobic reconstitution limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: 4 micromolar reductase, 20 micromolar MMACHC/CNCbl, 200 micromolar NADPH cross_nutrient: true evidence_location: Results: Figure 4; Materials and Methods: Decyanation of CNCbl [kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
Complete structured claim and evidence
Purified human MTRR coupled cob(II)alamin reduction to MMAB-dependent adenosylcobalamin synthesis in vitro.
Methionine synthase reductase / MTRR → Human ATP:cob(I)alamin adenosyltransferase / MMAB source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Indexed primary abstract
experimental_model
Purified human proteins
exposure
Purified MTRR plus MMAB and reductants
limitations
MTRR coupling in vitro does not identify the physiological mitochondrial electron donor.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Human MTRR supported B12 activation in a test-tube system; this does not establish its mitochondrial role.
primary_references
[leal-2004-human-mmab] Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/15347655/ DOI: 10.1074/jbc.m405449200
tissue_or_cell_type
Purified protein assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 991–1003
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human proteins · source_derived_draft · unverified_draft
### mtrr-supports-mmab-in-vitro Purified human MTRR coupled cob(II)alamin reduction to MMAB-dependent adenosylcobalamin synthesis in vitro. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human MTRR supported B12 activation in a test-tube system; this does not establish its mitochondrial role. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: MTRR coupling in vitro does not identify the physiological mitochondrial electron donor. exposure: Purified MTRR plus MMAB and reductants cross_nutrient: true evidence_location: Indexed primary abstract [leal-2004-human-mmab] Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/15347655/ DOI: 10.1074/jbc.m405449200
Complete structured claim and evidence
Cheilosis and angular stomatitis occurred during the low-niacin/tryptophan regimen even with approximately 2 mg/day total riboflavin and supplemental pyridoxine; these lesions were not specific evidence of B2 deficiency.
Niacin (vitamin B3) → Niacin-related oral mucosal injury source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Riboflavin (vitamin B2) (supplied_co_nutrient); Pyridoxine (supplied_co_nutrient)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 15452, "end_char": 16019, "text_sha256": "66c68d7739e59c3e98f30fe0757f468a7952746f7dfe082138dfa6727fa54bf4"}
experimental_model
Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra
exposure
Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan
limitations
Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A sore mouth can arise from different nutrient problems. The appearance alone did not identify which vitamin was lacking.
primary_references
[nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
supplementary_evidence_spans
[{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 8901, "end_char": 9290, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "59d1a659822aca95688b5e36bd07b41ea700bfbfdc92b40005acf11bd540b046", "locator": "Methods: supplied B-vitamin quantities"}, {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 31540, "end_char": 31811, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "ff226f4114a9dec08a00118aa9df933b8246dc89bcf362b2569c089b511d9d3e", "locator": "Discussion: riboflavin and pyridoxine supplements"}]
tissue_or_cell_type
Skin, oral and intestinal mucosa
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1205–1218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra · source_derived_draft · unverified_draft
### nia-clin-pellagra-riboflavin-context Cheilosis and angular stomatitis occurred during the low-niacin/tryptophan regimen even with approximately 2 mg/day total riboflavin and supplemental pyridoxine; these lesions were not specific evidence of B2 deficiency. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sore mouth can arise from different nutrient problems. The appearance alone did not identify which vitamin was lacking. organism: Homo sapiens tissue_or_cell_type: Skin, oral and intestinal mucosa experimental_model: Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra limitations: Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin. exposure: Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan cross_nutrient: Riboflavin (vitamin B2) (supplied_co_nutrient); Pyridoxine (supplied_co_nutrient) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 15452, "end_char": 16019, "text_sha256": "66c68d7739e59c3e98f30fe0757f468a7952746f7dfe082138dfa6727fa54bf4"} supplementary_evidence_spans: [{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 8901, "end_char": 9290, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "59d1a659822aca95688b5e36bd07b41ea700bfbfdc92b40005acf11bd540b046", "locator": "Methods: supplied B-vitamin quantities"}, {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 31540, "end_char": 31811, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "ff226f4114a9dec08a00118aa9df933b8246dc89bcf362b2569c089b511d9d3e", "locator": "Discussion: riboflavin and pyridoxine supplements"}] [nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
Complete structured claim and evidence
Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold.
2-prime-Deoxy-FMN → Iyd catalytic efficiency source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/37654510.txt", "start_char": 9069, "end_char": 10489, "text_sha256": "5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1", "text_characters": 1420, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN
exposure
Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1.
limitations
Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster.
primary_references
[iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. (2023). https://pubmed.ncbi.nlm.nih.gov/37654510/ DOI: 10.1039/d3cb00094j
tissue_or_cell_type
Purified enzyme
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 730–742
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN · source_derived_draft · unverified_draft
### iodine-syn-iyd-cofactor-substitution Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified enzyme experimental_model: Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN limitations: Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons. exposure: Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/37654510.txt", "start_char": 9069, "end_char": 10489, "text_sha256": "5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1", "text_characters": 1420, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. (2023). https://pubmed.ncbi.nlm.nih.gov/37654510/ DOI: 10.1039/d3cb00094j
Complete structured claim and evidence
Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays.
Human IYD lacking N-terminal membrane anchor → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 11103, "end_char": 12723, "text_sha256": "726c34262182d49a45a4741a29a49ef70bf6d529c79d75cfbb0e9ea59ffd256b", "text_characters": 1620, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
0–70 micromolar [125I]DIT; sodium dithionite supplies reducing equivalents.
limitations
Anchor-deleted enzyme and artificial reductant; does not identify the physiological electron donor.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
IYD recovers iodine from leftover iodinated tyrosine.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 688–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-dit-salvage Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD recovers iodine from leftover iodinated tyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Anchor-deleted enzyme and artificial reductant; does not identify the physiological electron donor. exposure: 0–70 micromolar [125I]DIT; sodium dithionite supplies reducing equivalents. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 11103, "end_char": 12723, "text_sha256": "726c34262182d49a45a4741a29a49ef70bf6d529c79d75cfbb0e9ea59ffd256b", "text_characters": 1620, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex.
Human IYD lacking N-terminal membrane anchor → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine.
limitations
Cofactor structure; no riboflavin restriction or supplementation study.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 702–714
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-fmn-binding Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Cofactor structure; no riboflavin restriction or supplementation study. exposure: Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro.
Human IYD patient variant proteins studied in 2008 → Iodotyrosine deiodination source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Four selected patients from three unrelated families plus in-vitro mutant enzyme assays
exposure
Two missense variants and one three-base-pair deletion; no nutrient-restriction experiment.
limitations
Abstract does not provide exact variant residues or assay dose.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens proteins
plain_language
Genetic defects can disable iodine recycling.
primary_references
[iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
tissue_or_cell_type
In-vitro enzyme assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 744–756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four selected patients from three unrelated families plus in-vitro mutant enzyme assays · source_derived_draft · unverified_draft
### iodine-syn-iyd-mutant-activity The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Genetic defects can disable iodine recycling. organism: Homo sapiens proteins tissue_or_cell_type: In-vitro enzyme assays experimental_model: Four selected patients from three unrelated families plus in-vitro mutant enzyme assays limitations: Abstract does not provide exact variant residues or assay dose. exposure: Two missense variants and one three-base-pair deletion; no nutrient-restriction experiment. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
Complete structured claim and evidence
The substrate analog 3-fluoro-L-tyrosine stabilized a one-electron-reduced FMN semiquinone during reductive titration of soluble human IYD.
3-Fluoro-L-tyrosine → FMN semiquinone source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 4223, "end_char": 4943, "text_sha256": "5567eccc06be2559ce51e8a2640697678a8fd3c1216896997568a9341da5a73b", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
Reductive titration with versus without active-site ligand.
limitations
An inert fluorotyrosine probe demonstrates cofactor control, not physiological fluoride displacement.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
Substrate-like binding changes which FMN redox state the enzyme can stabilize.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 716–728
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-redox-switch The substrate analog 3-fluoro-L-tyrosine stabilized a one-electron-reduced FMN semiquinone during reductive titration of soluble human IYD. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Substrate-like binding changes which FMN redox state the enzyme can stabilize. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: An inert fluorotyrosine probe demonstrates cofactor control, not physiological fluoride displacement. exposure: Reductive titration with versus without active-site ligand. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 4223, "end_char": 4943, "text_sha256": "5567eccc06be2559ce51e8a2640697678a8fd3c1216896997568a9341da5a73b", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
FAD-containing human GCDH dehydrogenates glutaryl-CoA through glutaconyl-CoA and decarboxylates it to crotonyl-CoA.
Glutaryl-CoA → Crotonyl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GCDH crystallography and substrate-mechanism analysis
limitations
The downstream shared ECHS1/HADH/ACAT1 reactions are separate records; these individual enzyme assays do not measure the full lysine-derived flux in a person.
organism
Homo sapiens
plain_language
GCDH shortens the lysine-derived carbon chain.
primary_references
[fu2004] Crystal Structures of Human Glutaryl-CoA Dehydrogenase with and without an Alternate Substrate: Structural Bases of Dehydrogenation and Decarboxylation Reactions (2004). https://pubs.acs.org/doi/10.1021/bi049290c DOI: 10.1021/bi049290c
tissue_or_cell_type
Mitochondrial matrix
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 136–144
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GCDH crystallography and substrate-mechanism analysis · source_derived_draft · unverified_draft
### gcdh-crotonyl-coa FAD-containing human GCDH dehydrogenates glutaryl-CoA through glutaconyl-CoA and decarboxylates it to crotonyl-CoA. Plain language: GCDH shortens the lysine-derived carbon chain. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Human GCDH crystallography and substrate-mechanism analysis limitations: The downstream shared ECHS1/HADH/ACAT1 reactions are separate records; these individual enzyme assays do not measure the full lysine-derived flux in a person. [fu2004] Crystal Structures of Human Glutaryl-CoA Dehydrogenase with and without an Alternate Substrate: Structural Bases of Dehydrogenation and Decarboxylation Reactions (2004). https://pubs.acs.org/doi/10.1021/bi049290c DOI: 10.1021/bi049290c
Complete structured claim and evidence
KDM1A/LSD1 oxidatively removes a methyl group from H3K4me2 through a flavin-dependent reaction.
KDM1A → Histone H3 dimethylated at K4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified LSD1 enzyme / histone assays and cellular RNA interference.
limitations
Do not extend this specific activity to trimethyllysine or every histone site. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
Some lysine methyl marks can be erased by a flavin enzyme.
primary_references
[lsd1-2004] Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 (2004). https://pubmed.ncbi.nlm.nih.gov/15620353/ DOI: 10.1016/j.cell.2004.12.012
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 557–565
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified LSD1 enzyme / histone assays and cellular RNA interference. · source_derived_draft · unverified_draft
### kdm1a-h3k4-demethylation KDM1A/LSD1 oxidatively removes a methyl group from H3K4me2 through a flavin-dependent reaction. Plain language: Some lysine methyl marks can be erased by a flavin enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified LSD1 enzyme / histone assays and cellular RNA interference. limitations: Do not extend this specific activity to trimethyllysine or every histone site. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [lsd1-2004] Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 (2004). https://pubmed.ncbi.nlm.nih.gov/15620353/ DOI: 10.1016/j.cell.2004.12.012
Complete structured claim and evidence
FAD supplied before a 46 C, five-minute incubation preserved more MTHFR activity than FAD added after heating.
FAD → Methylenetetrahydrofolate reductase / MTHFR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived FAD affects folate-enzyme stability.
experimental_model
Recombinant human MTHFR; kinetics and structures.
exposure
FAD before versus after heating
limitations
Heat challenge is not physiological riboflavin deficiency.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Flavin protected the enzyme during heat stress.
primary_references
[froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 447–458
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR; kinetics and structures. · source_derived_draft · unverified_draft
### folate-methyl-fad-heat-protection FAD supplied before a 46 C, five-minute incubation preserved more MTHFR activity than FAD added after heating. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Flavin protected the enzyme during heat stress. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human MTHFR; kinetics and structures. limitations: Heat challenge is not physiological riboflavin deficiency. exposure: FAD before versus after heating cross_nutrient: B2-derived FAD affects folate-enzyme stability. [froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
Complete structured claim and evidence
Dual SAM binding rearranged the human MTHFR linker and inserted a loop that blocked catalytic substrate access.
S-Adenosyl-L-methionine → Methylenetetrahydrofolate reductase / MTHFR source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human MTHFR; cryo-EM and biochemistry.
limitations
Not a whole-body SAM threshold.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
SAM switches MTHFR into a closed shape.
primary_references
[mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 460–469
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR; cryo-EM and biochemistry. · source_derived_draft · unverified_draft
### folate-methyl-sam-dual-binding Dual SAM binding rearranged the human MTHFR linker and inserted a loop that blocked catalytic substrate access. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: SAM switches MTHFR into a closed shape. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human MTHFR; cryo-EM and biochemistry. limitations: Not a whole-body SAM threshold. [mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y
Complete structured claim and evidence
Recombinant human PPCDC converted phosphopantothenoylcysteine to 4′-phosphopantetheine, verified by coupled enzyme assays and pathway reconstitution.
Phosphopantothenoylcysteine decarboxylase / PPCDC → 4′-Phosphopantothenoyl-L-cysteine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
Coupled assay used 50 micrograms/mL PPCDC with downstream COASY and 5 mM ATP; downstream ATP use is not assigned to PPCDC itself.
limitations
Coupled-assay confirmation and HPLC reconstitution; no dietary riboflavin depletion/repletion was tested.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
PPCDC removes the cysteine carboxyl group to produce the next CoA intermediate.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 548–559
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-ppcdc-decarboxylation Recombinant human PPCDC converted phosphopantothenoylcysteine to 4′-phosphopantetheine, verified by coupled enzyme assays and pathway reconstitution. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PPCDC removes the cysteine carboxyl group to produce the next CoA intermediate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Coupled-assay confirmation and HPLC reconstitution; no dietary riboflavin depletion/repletion was tested. exposure: Coupled assay used 50 micrograms/mL PPCDC with downstream COASY and 5 mM ATP; downstream ATP use is not assigned to PPCDC itself. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Purified recombinant human PPCDC showed flavin-like absorbance maxima at 382 and 458 nm and approximately equimolar FMN association.
Phosphopantothenoylcysteine decarboxylase / PPCDC → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
Purified human recombinant protein spectroscopy and cofactor characterization.
limitations
Direct enzyme-cofactor evidence; the study did not test dietary B2 deficiency, oral riboflavin rescue, or a universal FMN threshold. FMN origin from B2 is shared nutrient context, not a newly demonstrated dietary effect.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
The CoA pathway contains a direct biochemical connection to the B2 cofactor FMN.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 561–572
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-ppcdc-fmn Purified recombinant human PPCDC showed flavin-like absorbance maxima at 382 and 458 nm and approximately equimolar FMN association. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoA pathway contains a direct biochemical connection to the B2 cofactor FMN. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Direct enzyme-cofactor evidence; the study did not test dietary B2 deficiency, oral riboflavin rescue, or a universal FMN threshold. FMN origin from B2 is shared nutrient context, not a newly demonstrated dietary effect. exposure: Purified human recombinant protein spectroscopy and cofactor characterization. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Experimental RFVT3 silencing reduces uptake

Condition: machinery_impairment · SLC52A3-directed siRNA