Nutrient chapter

Vitamin B6

Vitamin B6 is a family of related compounds. Its active cofactor forms support amino-acid reactions, neurotransmitter synthesis, heme production and other pathways. Individual forms, deficiency, genetic impairment and excess exposure are recorded separately. Vitamin B6 vitamer family; pyridoxine, pyridoxal, pyridoxamine and their phosphorylated forms remain separate chemical entities.

130 recorded mechanisms · 35 availability situations · 1 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 jejunal perfusion and in-vitro assays demonstrated phosphatase-mediated hydrolysis of luminal PLP.
Intestinal PLP hydrolysis → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: hydrolysis, albumin and pH experiments
experimental_model
Rat jejunal perfusion and in-vitro phosphatase assays.
exposure
PLP hydrolysis tested across luminal pH and albumin concentrations.
limitations
Luminal disappearance is not a complete absorption balance; no specific human phosphatase is assigned.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
Intestinal phosphatases remove PLP phosphate.
primary_references
[middleton1986] Intestinal hydrolysis of pyridoxal 5'-phosphate in vitro and in vivo in the rat. Effect of protein binding and pH. (1986). https://pubmed.ncbi.nlm.nih.gov/3721120/ DOI: 10.1016/0016-5085(86)90567-6
tissue_or_cell_type
Jejunum
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 72–83
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat jejunal perfusion and in-vitro phosphatase assays. · source_derived_draft · unverified_draft
### b6-transport-gut-plp-hydrolysis Rat jejunal perfusion and in-vitro assays demonstrated phosphatase-mediated hydrolysis of luminal PLP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intestinal phosphatases remove PLP phosphate. organism: Rattus norvegicus tissue_or_cell_type: Jejunum experimental_model: Rat jejunal perfusion and in-vitro phosphatase assays. limitations: Luminal disappearance is not a complete absorption balance; no specific human phosphatase is assigned. exposure: PLP hydrolysis tested across luminal pH and albumin concentrations. evidence_location: Indexed abstract: hydrolysis, albumin and pH experiments [middleton1986] Intestinal hydrolysis of pyridoxal 5'-phosphate in vitro and in vivo in the rat. Effect of protein binding and pH. (1986). https://pubmed.ncbi.nlm.nih.gov/3721120/ DOI: 10.1016/0016-5085(86)90567-6
Complete structured claim and evidence
Albumin binding inhibited hydrolysis of 2 micromolar PLP at pH 5-7.4; at pH 3-4 binding was negligible and hydrolysis persisted.
PLP → Intestinal PLP hydrolysis source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: hydrolysis, albumin and pH experiments
experimental_model
Rat jejunal perfusion and in-vitro phosphatase assays.
exposure
2 micromolar PLP, albumin and pH manipulation.
limitations
Albumin species is not assigned from the indexed abstract; no human acid-suppression outcome was measured.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
Protein binding and acidity changed substrate access.
primary_references
[middleton1986] Intestinal hydrolysis of pyridoxal 5'-phosphate in vitro and in vivo in the rat. Effect of protein binding and pH. (1986). https://pubmed.ncbi.nlm.nih.gov/3721120/ DOI: 10.1016/0016-5085(86)90567-6
tissue_or_cell_type
Perfused jejunum and in-vitro preparations
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 85–96
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat jejunal perfusion and in-vitro phosphatase assays. · source_derived_draft · unverified_draft
### b6-transport-albumin-gut-hydrolysis Albumin binding inhibited hydrolysis of 2 micromolar PLP at pH 5-7.4; at pH 3-4 binding was negligible and hydrolysis persisted. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protein binding and acidity changed substrate access. organism: Rattus norvegicus tissue_or_cell_type: Perfused jejunum and in-vitro preparations experimental_model: Rat jejunal perfusion and in-vitro phosphatase assays. limitations: Albumin species is not assigned from the indexed abstract; no human acid-suppression outcome was measured. exposure: 2 micromolar PLP, albumin and pH manipulation. evidence_location: Indexed abstract: hydrolysis, albumin and pH experiments [middleton1986] Intestinal hydrolysis of pyridoxal 5'-phosphate in vitro and in vivo in the rat. Effect of protein binding and pH. (1986). https://pubmed.ncbi.nlm.nih.gov/3721120/ DOI: 10.1016/0016-5085(86)90567-6
Complete structured claim and evidence
Hydrolysis-protected rat intestinal sacs showed serosal PLP appearance; the authors interpreted accompanying venous data as supporting some direct phosphorylated-PLP absorption.
PLP → Intestinal PLP absorption source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: hydrolysis-protected sac experiments and in-situ sampling
experimental_model
Rat everted intestinal sacs and mesenteric venous sampling.
exposure
Physiological-range 0.1-1 micromolar PLP and additional concentration-response experiments.
limitations
Does not establish the quantitative contribution in humans or exclude hydrolysis/rephosphorylation in every preparation.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
A rat experiment suggests PLP can sometimes cross intact.
primary_references
[morita1988] Intestinal absorption of pyridoxal 5'-phosphate at physiological levels in rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3244043/ DOI: 10.3177/jnsv.34.553
tissue_or_cell_type
Small intestine
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 98–109
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat everted intestinal sacs and mesenteric venous sampling. · source_derived_draft · unverified_draft
### b6-transport-rat-direct-plp Hydrolysis-protected rat intestinal sacs showed serosal PLP appearance; the authors interpreted accompanying venous data as supporting some direct phosphorylated-PLP absorption. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A rat experiment suggests PLP can sometimes cross intact. organism: Rattus norvegicus tissue_or_cell_type: Small intestine experimental_model: Rat everted intestinal sacs and mesenteric venous sampling. limitations: Does not establish the quantitative contribution in humans or exclude hydrolysis/rephosphorylation in every preparation. exposure: Physiological-range 0.1-1 micromolar PLP and additional concentration-response experiments. evidence_location: Indexed abstract: hydrolysis-protected sac experiments and in-situ sampling [morita1988] Intestinal absorption of pyridoxal 5'-phosphate at physiological levels in rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3244043/ DOI: 10.3177/jnsv.34.553
Complete structured claim and evidence
Caco-2 pyridoxine uptake was energy-dependent and sodium-independent; saturation occurred at pH 5.5 (apparent Km 11.99 micromolar), but not pH 7.4.
Pyridoxine → Intestinal pyridoxine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: pH-dependent saturation and sodium independence
experimental_model
Human Caco-2 intestinal epithelial cells.
exposure
Radiotracer uptake at controlled extracellular pH.
limitations
Carrier identity was not established; uptake behavior alone does not identify a transporter gene.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Acidic conditions exposed a saturable uptake component.
primary_references
[said2003] A carrier-mediated mechanism for pyridoxine uptake by human intestinal epithelial Caco-2 cells: regulation by a PKA-mediated pathway. (2003). https://pubmed.ncbi.nlm.nih.gov/12867360/ DOI: 10.1152/ajpcell.00204.2003
tissue_or_cell_type
Caco-2 cells
Vitamin B6: 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 · Human Caco-2 intestinal epithelial cells. · source_derived_draft · unverified_draft
### b6-transport-caco2-pn-uptake Caco-2 pyridoxine uptake was energy-dependent and sodium-independent; saturation occurred at pH 5.5 (apparent Km 11.99 micromolar), but not pH 7.4. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acidic conditions exposed a saturable uptake component. organism: Homo sapiens tissue_or_cell_type: Caco-2 cells experimental_model: Human Caco-2 intestinal epithelial cells. limitations: Carrier identity was not established; uptake behavior alone does not identify a transporter gene. exposure: Radiotracer uptake at controlled extracellular pH. evidence_location: Indexed abstract: pH-dependent saturation and sodium independence [said2003] A carrier-mediated mechanism for pyridoxine uptake by human intestinal epithelial Caco-2 cells: regulation by a PKA-mediated pathway. (2003). https://pubmed.ncbi.nlm.nih.gov/12867360/ DOI: 10.1152/ajpcell.00204.2003
Complete structured claim and evidence
Polarized Caco-2 cells supplied apically with PN generated PL and released more PL basolaterally than apically.
Pyridoxine → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
evidence_location
Results: Incubation with pyridoxine; Figure 4
experimental_model
Polarized human Caco-2 monolayers; human intestinal lysates.
exposure
100 or 1000 nM PN; 6-48 h.
limitations
Vitamer measurements establish net conversion; individual enzyme fluxes were not separately perturbed.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Enterocytes can process a precursor before releasing pyridoxal.
primary_references
[albersen2013] The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. (2013). https://pubmed.ncbi.nlm.nih.gov/23342087/ DOI: 10.1371/journal.pone.0054113
tissue_or_cell_type
Polarized Caco-2 monolayers
Vitamin B6: 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 · Polarized human Caco-2 monolayers; human intestinal lysates. · source_derived_draft · unverified_draft
### b6-transport-enterocyte-pn-to-pl Polarized Caco-2 cells supplied apically with PN generated PL and released more PL basolaterally than apically. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Enterocytes can process a precursor before releasing pyridoxal. organism: Homo sapiens tissue_or_cell_type: Polarized Caco-2 monolayers experimental_model: Polarized human Caco-2 monolayers; human intestinal lysates. limitations: Vitamer measurements establish net conversion; individual enzyme fluxes were not separately perturbed. exposure: 100 or 1000 nM PN; 6-48 h. evidence_location: Results: Incubation with pyridoxine; Figure 4 [albersen2013] The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. (2013). https://pubmed.ncbi.nlm.nih.gov/23342087/ DOI: 10.1371/journal.pone.0054113
Complete structured claim and evidence
Polarized Caco-2 cells supplied apically with PM generated PL and released more PL basolaterally than apically.
Pyridoxamine → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
evidence_location
Results: Incubation with pyridoxamine; Figure 4
experimental_model
Polarized human Caco-2 monolayers; human intestinal lysates.
exposure
100 or 1000 nM PM; 6-48 h.
limitations
Vitamer measurements establish net conversion; individual enzyme fluxes were not separately perturbed.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Enterocytes can process a precursor before releasing pyridoxal.
primary_references
[albersen2013] The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. (2013). https://pubmed.ncbi.nlm.nih.gov/23342087/ DOI: 10.1371/journal.pone.0054113
tissue_or_cell_type
Polarized Caco-2 monolayers
Vitamin B6: 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 · Polarized human Caco-2 monolayers; human intestinal lysates. · source_derived_draft · unverified_draft
### b6-transport-enterocyte-pm-to-pl Polarized Caco-2 cells supplied apically with PM generated PL and released more PL basolaterally than apically. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Enterocytes can process a precursor before releasing pyridoxal. organism: Homo sapiens tissue_or_cell_type: Polarized Caco-2 monolayers experimental_model: Polarized human Caco-2 monolayers; human intestinal lysates. limitations: Vitamer measurements establish net conversion; individual enzyme fluxes were not separately perturbed. exposure: 100 or 1000 nM PM; 6-48 h. evidence_location: Results: Incubation with pyridoxamine; Figure 4 [albersen2013] The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. (2013). https://pubmed.ncbi.nlm.nih.gov/23342087/ DOI: 10.1371/journal.pone.0054113
Complete structured claim and evidence
During apical PL incubation, basolateral PL appearance approximately matched apical disappearance, without detectable medium PLP or PMP.
Pyridoxal → Intestinal pyridoxal translocation source_derived_draftungraded
Experimental context and source evidence
evidence_location
Results: Incubation with pyridoxal; Table 1
experimental_model
Polarized human Caco-2 monolayers; human intestinal lysates.
exposure
100 or 1000 nM PL; 6-48 h.
limitations
Cell monolayer model; PL and PN transport mechanisms need not be identical.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Pyridoxal crossed the cell layer largely as pyridoxal.
primary_references
[albersen2013] The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. (2013). https://pubmed.ncbi.nlm.nih.gov/23342087/ DOI: 10.1371/journal.pone.0054113
tissue_or_cell_type
Polarized Caco-2 monolayers
Vitamin B6: 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 · Polarized human Caco-2 monolayers; human intestinal lysates. · source_derived_draft · unverified_draft
### b6-transport-enterocyte-pl-translocation During apical PL incubation, basolateral PL appearance approximately matched apical disappearance, without detectable medium PLP or PMP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pyridoxal crossed the cell layer largely as pyridoxal. organism: Homo sapiens tissue_or_cell_type: Polarized Caco-2 monolayers experimental_model: Polarized human Caco-2 monolayers; human intestinal lysates. limitations: Cell monolayer model; PL and PN transport mechanisms need not be identical. exposure: 100 or 1000 nM PL; 6-48 h. evidence_location: Results: Incubation with pyridoxal; Table 1 [albersen2013] The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. (2013). https://pubmed.ncbi.nlm.nih.gov/23342087/ DOI: 10.1371/journal.pone.0054113
Complete structured claim and evidence
Purified recombinant human PDXK phosphorylated pyridoxine to its corresponding 5-prime phosphate.
Pyridoxal kinase / PDXK → Pyridoxine source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract and publisher abstract; human enzyme findings only
experimental_model
Purified recombinant human and E. coli pyridoxal kinases.
exposure
Purified-enzyme substrate kinetics.
limitations
Model-specific evidence; no dietary threshold or treatment benefit established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
PDXK adds phosphate to this B6 precursor.
primary_references
[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
tissue_or_cell_type
Purified human enzyme
Vitamin B6: 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 · Purified recombinant human and E. coli pyridoxal kinases. · source_derived_draft · unverified_draft
### b6-transport-pdxk-pn Purified recombinant human PDXK phosphorylated pyridoxine to its corresponding 5-prime phosphate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PDXK adds phosphate to this B6 precursor. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Model-specific evidence; no dietary threshold or treatment benefit established. exposure: Purified-enzyme substrate kinetics. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
Complete structured claim and evidence
Purified recombinant human PDXK phosphorylated pyridoxamine to its corresponding 5-prime phosphate.
Pyridoxal kinase / PDXK → Pyridoxamine source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract and publisher abstract; human enzyme findings only
experimental_model
Purified recombinant human and E. coli pyridoxal kinases.
exposure
Purified-enzyme substrate kinetics.
limitations
Model-specific evidence; no dietary threshold or treatment benefit established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
PDXK adds phosphate to this B6 precursor.
primary_references
[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
tissue_or_cell_type
Purified human enzyme
Vitamin B6: 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 · Purified recombinant human and E. coli pyridoxal kinases. · source_derived_draft · unverified_draft
### b6-transport-pdxk-pm Purified recombinant human PDXK phosphorylated pyridoxamine to its corresponding 5-prime phosphate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PDXK adds phosphate to this B6 precursor. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Model-specific evidence; no dietary threshold or treatment benefit established. exposure: Purified-enzyme substrate kinetics. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
Complete structured claim and evidence
Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions.
Magnesium-ATP complex → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-B6 activation chemistry.
evidence_location
Indexed abstract and publisher abstract; human enzyme findings only
experimental_model
Purified recombinant human and E. coli pyridoxal kinases.
exposure
MgATP versus ZnATP kinetic comparisons.
limitations
Metal preference depends on assay conditions and does not prove magnesium supplementation improves B6 status.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Magnesium helps supply ATP to B6 activation.
primary_references
[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
tissue_or_cell_type
Purified human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 189–201
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human and E. coli pyridoxal kinases. · source_derived_draft · unverified_draft
### b6-transport-pdxk-mgatp Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps supply ATP to B6 activation. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Metal preference depends on assay conditions and does not prove magnesium supplementation improves B6 status. exposure: MgATP versus ZnATP kinetic comparisons. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only cross_nutrient: Magnesium-B6 activation chemistry. [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
Complete structured claim and evidence
Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity.
Potassium ion → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Potassium/sodium-B6 enzyme kinetics.
evidence_location
Full text: Metal binding and enzyme activity; Figure 1
experimental_model
Purified recombinant human PDXK kinetics and crystallography.
exposure
Kinetic assays at pH 7.3.
limitations
Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Potassium and sodium affect different kinetic properties.
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 human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 203–215
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PDXK kinetics and crystallography. · source_derived_draft · unverified_draft
### b6-transport-pdxk-k-na Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and sodium affect different kinetic properties. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human PDXK kinetics and crystallography. limitations: Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects. exposure: Kinetic assays at pH 7.3. evidence_location: Full text: Metal binding and enzyme activity; Figure 1 cross_nutrient: Potassium/sodium-B6 enzyme kinetics. [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
ATPgammaS binding was detected for wild-type PDXK but not A228T under the ITC conditions; A228T also required higher MgATP for half-maximal activity.
Human PDXK Ala228Thr → ATP gamma S source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 3B,E
experimental_model
Human families, dried blood spots, recombinant PDXK variants.
exposure
ATPgammaS ITC; variable MgATP kinetics.
limitations
ATPgammaS is an analog; absence of detectable binding is assay-specific.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The variant disrupts nucleotide handling.
primary_references
[chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
tissue_or_cell_type
Purified human enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 217–228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human families, dried blood spots, recombinant PDXK variants. · source_derived_draft · unverified_draft
### b6-transport-pdxk-a228t-atp ATPgammaS binding was detected for wild-type PDXK but not A228T under the ITC conditions; A228T also required higher MgATP for half-maximal activity. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The variant disrupts nucleotide handling. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Human families, dried blood spots, recombinant PDXK variants. limitations: ATPgammaS is an analog; absence of detectable binding is assay-specific. exposure: ATPgammaS ITC; variable MgATP kinetics. evidence_location: Figure 3B,E [chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
Complete structured claim and evidence
Homozygous A228T cases had PDXK activities of 0.8 and 1.1 pmol per dried-blood-spot punch per hour; controls ranged 2.6-14.7.
Human PDXK Ala228Thr homozygous genotype → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 3F; Results
experimental_model
Human families, dried blood spots, recombinant PDXK variants.
exposure
Patient blood-spot assay.
limitations
Assay-specific values.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Inherited activation defects reduced enzyme output.
primary_references
[chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
tissue_or_cell_type
Erythrocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 230–241
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human families, dried blood spots, recombinant PDXK variants. · source_derived_draft · unverified_draft
### b6-transport-pdxk-patient-a228t Homozygous A228T cases had PDXK activities of 0.8 and 1.1 pmol per dried-blood-spot punch per hour; controls ranged 2.6-14.7. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited activation defects reduced enzyme output. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human families, dried blood spots, recombinant PDXK variants. limitations: Assay-specific values. exposure: Patient blood-spot assay. evidence_location: Figure 3F; Results [chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
Complete structured claim and evidence
Homozygous R220Q cases had PDXK activities of 0.5 and 1.19 pmol per dried-blood-spot punch per hour; controls ranged 2.6-14.7.
Human PDXK Arg220Gln homozygous genotype → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 3F; Results
experimental_model
Human families, dried blood spots, recombinant PDXK variants.
exposure
Patient blood-spot assay.
limitations
Assay-specific values.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Inherited activation defects reduced enzyme output.
primary_references
[chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
tissue_or_cell_type
Erythrocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 243–254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human families, dried blood spots, recombinant PDXK variants. · source_derived_draft · unverified_draft
### b6-transport-pdxk-patient-r220q Homozygous R220Q cases had PDXK activities of 0.5 and 1.19 pmol per dried-blood-spot punch per hour; controls ranged 2.6-14.7. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited activation defects reduced enzyme output. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human families, dried blood spots, recombinant PDXK variants. limitations: Assay-specific values. exposure: Patient blood-spot assay. evidence_location: Figure 3F; Results [chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
Complete structured claim and evidence
Catalytically active recombinant human pyridoxal phosphatase hydrolyzed pyridoxal-phosphate.
Human pyridoxal phosphatase / PDXP → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: cloning and substrate hydrolysis
experimental_model
Recombinant human pyridoxal phosphatase expressed in E. coli.
exposure
Recombinant-enzyme characterization.
limitations
Model-specific evidence; no dietary threshold or treatment benefit established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
PDXP removes phosphate from a B6 vitamer.
primary_references
[jang2003] Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. (2003). https://pubmed.ncbi.nlm.nih.gov/14522954/ DOI: 10.1074/jbc.m309619200
tissue_or_cell_type
Purified recombinant human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 256–267
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human pyridoxal phosphatase expressed in E. coli. · source_derived_draft · unverified_draft
### b6-transport-pdxp-plp Catalytically active recombinant human pyridoxal phosphatase hydrolyzed pyridoxal-phosphate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PDXP removes phosphate from a B6 vitamer. organism: Homo sapiens tissue_or_cell_type: Purified recombinant human enzyme experimental_model: Recombinant human pyridoxal phosphatase expressed in E. coli. limitations: Model-specific evidence; no dietary threshold or treatment benefit established. exposure: Recombinant-enzyme characterization. evidence_location: Indexed abstract: cloning and substrate hydrolysis [jang2003] Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. (2003). https://pubmed.ncbi.nlm.nih.gov/14522954/ DOI: 10.1074/jbc.m309619200
Complete structured claim and evidence
Catalytically active recombinant human pyridoxal phosphatase hydrolyzed pyridoxine-phosphate.
Human pyridoxal phosphatase / PDXP → Pyridoxine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: cloning and substrate hydrolysis
experimental_model
Recombinant human pyridoxal phosphatase expressed in E. coli.
exposure
Recombinant-enzyme characterization.
limitations
Model-specific evidence; no dietary threshold or treatment benefit established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
PDXP removes phosphate from a B6 vitamer.
primary_references
[jang2003] Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. (2003). https://pubmed.ncbi.nlm.nih.gov/14522954/ DOI: 10.1074/jbc.m309619200
tissue_or_cell_type
Purified recombinant human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 269–280
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human pyridoxal phosphatase expressed in E. coli. · source_derived_draft · unverified_draft
### b6-transport-pdxp-pnp Catalytically active recombinant human pyridoxal phosphatase hydrolyzed pyridoxine-phosphate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PDXP removes phosphate from a B6 vitamer. organism: Homo sapiens tissue_or_cell_type: Purified recombinant human enzyme experimental_model: Recombinant human pyridoxal phosphatase expressed in E. coli. limitations: Model-specific evidence; no dietary threshold or treatment benefit established. exposure: Recombinant-enzyme characterization. evidence_location: Indexed abstract: cloning and substrate hydrolysis [jang2003] Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. (2003). https://pubmed.ncbi.nlm.nih.gov/14522954/ DOI: 10.1074/jbc.m309619200
Complete structured claim and evidence
Human erythrocyte pyridoxal phosphatase required divalent cations; magnesium activated PLP hydrolysis with Michaelis-Menten behavior.
Mg2+ → Human pyridoxal phosphatase / PDXP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium participates in both sides of B6 phosphate cycling.
evidence_location
Indexed abstract: divalent-cation kinetics at pH 7.4, 37 C
experimental_model
Purified human erythrocyte pyridoxal phosphatase kinetics.
exposure
pH 7.4, 37 C; Mg2+ titration.
limitations
Other metals also activated in vitro; does not establish net PLP response to changing dietary magnesium.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Magnesium supports B6 dephosphorylation as well as activation.
primary_references
[fonda1995] Kinetic mechanism and divalent metal activation of human erythrocyte pyridoxal phosphatase. (1995). https://pubmed.ncbi.nlm.nih.gov/7625842/ DOI: 10.1016/0003-9861(95)90018-7
tissue_or_cell_type
Erythrocyte enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 282–294
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human erythrocyte pyridoxal phosphatase kinetics. · source_derived_draft · unverified_draft
### b6-transport-pdxp-magnesium Human erythrocyte pyridoxal phosphatase required divalent cations; magnesium activated PLP hydrolysis with Michaelis-Menten behavior. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports B6 dephosphorylation as well as activation. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Purified human erythrocyte pyridoxal phosphatase kinetics. limitations: Other metals also activated in vitro; does not establish net PLP response to changing dietary magnesium. exposure: pH 7.4, 37 C; Mg2+ titration. evidence_location: Indexed abstract: divalent-cation kinetics at pH 7.4, 37 C cross_nutrient: Magnesium participates in both sides of B6 phosphate cycling. [fonda1995] Kinetic mechanism and divalent metal activation of human erythrocyte pyridoxal phosphatase. (1995). https://pubmed.ncbi.nlm.nih.gov/7625842/ DOI: 10.1016/0003-9861(95)90018-7
Complete structured claim and evidence
Ubiquitous Pdxp deletion raised PLP in brain, skeletal muscle and red cells by up to threefold compared with controls.
Mouse Pdxp knockout genotype → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Indexed abstract: tissue PLP measurements
experimental_model
Conditional and ubiquitous Pdxp-deletion mice.
exposure
Genetic Pdxp ablation.
limitations
Effects vary by tissue; knockout does not model ordinary B6 intake.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Mus musculus
plain_language
Slower breakdown increased tissue PLP.
primary_references
[jeanclos2019] Improved cognition, mild anxiety-like behavior and decreased motor performance in pyridoxal phosphatase-deficient mice. (2019). https://pubmed.ncbi.nlm.nih.gov/30327125/ DOI: 10.1016/j.bbadis.2018.08.018
tissue_or_cell_type
Brain, skeletal muscle and erythrocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 296–307
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional and ubiquitous Pdxp-deletion mice. · source_derived_draft · unverified_draft
### b6-transport-pdxp-mouse-pools Ubiquitous Pdxp deletion raised PLP in brain, skeletal muscle and red cells by up to threefold compared with controls. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Slower breakdown increased tissue PLP. organism: Mus musculus tissue_or_cell_type: Brain, skeletal muscle and erythrocytes experimental_model: Conditional and ubiquitous Pdxp-deletion mice. limitations: Effects vary by tissue; knockout does not model ordinary B6 intake. exposure: Genetic Pdxp ablation. evidence_location: Indexed abstract: tissue PLP measurements [jeanclos2019] Improved cognition, mild anxiety-like behavior and decreased motor performance in pyridoxal phosphatase-deficient mice. (2019). https://pubmed.ncbi.nlm.nih.gov/30327125/ DOI: 10.1016/j.bbadis.2018.08.018
Complete structured claim and evidence
Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity
experimental_model
Normal and hypophosphatasia human skin fibroblasts.
exposure
Extracellular PLP; intact versus disrupted cells; PI-PLC release.
limitations
Directly demonstrated in fibroblasts; does not itself measure brain entry.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Cell-surface ALPL processes PLP outside the cell.
primary_references
[fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
tissue_or_cell_type
Skin fibroblasts
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 309–320
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal and hypophosphatasia human skin fibroblasts. · source_derived_draft · unverified_draft
### b6-transport-alpl-ecto Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cell-surface ALPL processes PLP outside the cell. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts experimental_model: Normal and hypophosphatasia human skin fibroblasts. limitations: Directly demonstrated in fibroblasts; does not itself measure brain entry. exposure: Extracellular PLP; intact versus disrupted cells; PI-PLC release. evidence_location: Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity [fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
Complete structured claim and evidence
Hypophosphatasia fibroblasts retained only 2-5% of control phosphatase activity toward PLP and other tested substrates.
Human hypophosphatasia ALPL impairment → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity
experimental_model
Normal and hypophosphatasia human skin fibroblasts.
exposure
Patient versus control fibroblast enzyme assays.
limitations
Not an intake-deficiency experiment.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A handling defect limits extracellular PLP processing.
primary_references
[fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
tissue_or_cell_type
Skin fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 322–333
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal and hypophosphatasia human skin fibroblasts. · source_derived_draft · unverified_draft
### b6-transport-alpl-impaired Hypophosphatasia fibroblasts retained only 2-5% of control phosphatase activity toward PLP and other tested substrates. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A handling defect limits extracellular PLP processing. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts experimental_model: Normal and hypophosphatasia human skin fibroblasts. limitations: Not an intake-deficiency experiment. exposure: Patient versus control fibroblast enzyme assays. evidence_location: Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity [fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
Complete structured claim and evidence
Equilibrium dialysis found one higher-affinity human-albumin PLP-binding site (Kd 8.7 micromolar) and additional lower-affinity sites.
Human serum albumin → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: equilibrium dialysis and competition
experimental_model
Purified human serum albumin binding assays.
exposure
In-vitro albumin/PLP binding.
limitations
Purified-system affinity is not a plasma sufficiency threshold; bovine albumin behaved differently.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Albumin binds circulating active B6.
primary_references
[fonda1991] The binding of pyridoxal 5'-phosphate to human serum albumin. (1991). https://pubmed.ncbi.nlm.nih.gov/1898027/ DOI: 10.1016/0003-9861(91)90167-h
tissue_or_cell_type
Purified serum albumin
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 335–346
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human serum albumin binding assays. · source_derived_draft · unverified_draft
### b6-transport-albumin-binding Equilibrium dialysis found one higher-affinity human-albumin PLP-binding site (Kd 8.7 micromolar) and additional lower-affinity sites. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Albumin binds circulating active B6. organism: Homo sapiens tissue_or_cell_type: Purified serum albumin experimental_model: Purified human serum albumin binding assays. limitations: Purified-system affinity is not a plasma sufficiency threshold; bovine albumin behaved differently. exposure: In-vitro albumin/PLP binding. evidence_location: Indexed abstract: equilibrium dialysis and competition [fonda1991] The binding of pyridoxal 5'-phosphate to human serum albumin. (1991). https://pubmed.ncbi.nlm.nih.gov/1898027/ DOI: 10.1016/0003-9861(91)90167-h
Complete structured claim and evidence
Pyridoxal and 4-pyridoxic acid inhibited PLP binding to human serum albumin in vitro.
Pyridoxal → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: equilibrium dialysis and competition
experimental_model
Purified human serum albumin binding assays.
exposure
In-vitro binding-inhibition experiments.
limitations
Physiological competition magnitude and consequences were not established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Related B6 molecules can compete in albumin-binding assays.
primary_references
[fonda1991] The binding of pyridoxal 5'-phosphate to human serum albumin. (1991). https://pubmed.ncbi.nlm.nih.gov/1898027/ DOI: 10.1016/0003-9861(91)90167-h
tissue_or_cell_type
Purified serum albumin
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 348–359
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human serum albumin binding assays. · source_derived_draft · unverified_draft
### b6-transport-albumin-competition Pyridoxal and 4-pyridoxic acid inhibited PLP binding to human serum albumin in vitro. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related B6 molecules can compete in albumin-binding assays. organism: Homo sapiens tissue_or_cell_type: Purified serum albumin experimental_model: Purified human serum albumin binding assays. limitations: Physiological competition magnitude and consequences were not established. exposure: In-vitro binding-inhibition experiments. evidence_location: Indexed abstract: equilibrium dialysis and competition [fonda1991] The binding of pyridoxal 5'-phosphate to human serum albumin. (1991). https://pubmed.ncbi.nlm.nih.gov/1898027/ DOI: 10.1016/0003-9861(91)90167-h
Complete structured claim and evidence
The human PNPO IVS3-1G>A splice-site construct had no detectable PNPO activity in the reported CHO expression assay.
Human PNPO IVS3-1G>A splice genotype → Pyridoxine 5-prime-phosphate oxidase / PNPO source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Indexed abstract: CHO expression studies
experimental_model
Five affected patients and human PNPO constructs expressed in CHO cells.
exposure
Construct expression, not nutrient withdrawal.
limitations
Cannot generalize to every PNPO variant or vitamer treatment response.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens protein expressed in Cricetulus griseus cells
plain_language
This variant prevented measured B6 activation.
primary_references
[mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120
tissue_or_cell_type
CHO expression system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 361–372
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five affected patients and human PNPO constructs expressed in CHO cells. · source_derived_draft · unverified_draft
### b6-transport-pnpo-splice The human PNPO IVS3-1G>A splice-site construct had no detectable PNPO activity in the reported CHO expression assay. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant prevented measured B6 activation. organism: Homo sapiens protein expressed in Cricetulus griseus cells tissue_or_cell_type: CHO expression system experimental_model: Five affected patients and human PNPO constructs expressed in CHO cells. limitations: Cannot generalize to every PNPO variant or vitamer treatment response. exposure: Construct expression, not nutrient withdrawal. evidence_location: Indexed abstract: CHO expression studies [mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120
Complete structured claim and evidence
The human PNPO X262Q stop-loss construct had no detectable PNPO activity in the reported CHO expression assay.
Human PNPO stop262Gln genotype → Pyridoxine 5-prime-phosphate oxidase / PNPO source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Indexed abstract: CHO expression studies
experimental_model
Five affected patients and human PNPO constructs expressed in CHO cells.
exposure
Construct expression, not nutrient withdrawal.
limitations
Cannot generalize to every PNPO variant or vitamer treatment response.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens protein expressed in Cricetulus griseus cells
plain_language
This variant prevented measured B6 activation.
primary_references
[mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120
tissue_or_cell_type
CHO expression system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 374–385
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five affected patients and human PNPO constructs expressed in CHO cells. · source_derived_draft · unverified_draft
### b6-transport-pnpo-stoploss The human PNPO X262Q stop-loss construct had no detectable PNPO activity in the reported CHO expression assay. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant prevented measured B6 activation. organism: Homo sapiens protein expressed in Cricetulus griseus cells tissue_or_cell_type: CHO expression system experimental_model: Five affected patients and human PNPO constructs expressed in CHO cells. limitations: Cannot generalize to every PNPO variant or vitamer treatment response. exposure: Construct expression, not nutrient withdrawal. evidence_location: Indexed abstract: CHO expression studies [mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120
Complete structured claim and evidence
Mass spectrometry of reduced recombinant human PLPBP identified Lys47 as the PLP-binding residue; spectroscopy supported an internal aldimine.
Human PLP-binding protein / PLPBP → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Figure 1C-D
experimental_model
Recombinant human PLPBP and HEK293 proteomics.
exposure
NaBH4 reduction, LC-MS/MS and spectral analysis.
limitations
Binding alone does not prove direct cofactor delivery to target enzymes.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
PLPBP physically binds PLP through a lysine residue.
primary_references
[fux2020] Biochemical and Proteomic Studies of Human Pyridoxal 5'-Phosphate-Binding Protein (PLPBP). (2020). https://pubmed.ncbi.nlm.nih.gov/31825581/ DOI: 10.1021/acschembio.9b00857
tissue_or_cell_type
Recombinant human protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 387–398
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PLPBP and HEK293 proteomics. · source_derived_draft · unverified_draft
### b6-transport-plpbp-binding Mass spectrometry of reduced recombinant human PLPBP identified Lys47 as the PLP-binding residue; spectroscopy supported an internal aldimine. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PLPBP physically binds PLP through a lysine residue. organism: Homo sapiens tissue_or_cell_type: Recombinant human protein experimental_model: Recombinant human PLPBP and HEK293 proteomics. limitations: Binding alone does not prove direct cofactor delivery to target enzymes. exposure: NaBH4 reduction, LC-MS/MS and spectral analysis. evidence_location: Figure 1C-D [fux2020] Biochemical and Proteomic Studies of Human Pyridoxal 5'-Phosphate-Binding Protein (PLPBP). (2020). https://pubmed.ncbi.nlm.nih.gov/31825581/ DOI: 10.1021/acschembio.9b00857
Complete structured claim and evidence
Purified R241Q lacked detectable bound PLP, but a fourfold molar PLP excess produced a mixture including holo-protein.
Human PLPBP Arg241Gln → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Full text: biochemical properties and Figure 2B-D
experimental_model
Recombinant human PLPBP and HEK293 proteomics.
exposure
Purification followed by PLP addition.
limitations
Biochemical reconstitution does not establish clinical rescue.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This variant binds poorly but is not absolutely incapable of binding.
primary_references
[fux2020] Biochemical and Proteomic Studies of Human Pyridoxal 5'-Phosphate-Binding Protein (PLPBP). (2020). https://pubmed.ncbi.nlm.nih.gov/31825581/ DOI: 10.1021/acschembio.9b00857
tissue_or_cell_type
Recombinant human protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 400–411
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PLPBP and HEK293 proteomics. · source_derived_draft · unverified_draft
### b6-transport-plpbp-r241q Purified R241Q lacked detectable bound PLP, but a fourfold molar PLP excess produced a mixture including holo-protein. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant binds poorly but is not absolutely incapable of binding. organism: Homo sapiens tissue_or_cell_type: Recombinant human protein experimental_model: Recombinant human PLPBP and HEK293 proteomics. limitations: Biochemical reconstitution does not establish clinical rescue. exposure: Purification followed by PLP addition. evidence_location: Full text: biochemical properties and Figure 2B-D [fux2020] Biochemical and Proteomic Studies of Human Pyridoxal 5'-Phosphate-Binding Protein (PLPBP). (2020). https://pubmed.ncbi.nlm.nih.gov/31825581/ DOI: 10.1021/acschembio.9b00857
Complete structured claim and evidence
PLPBP-deficient patient fibroblasts in Darin 2016 accumulated approximately two- to threefold more PLP than controls in the tested culture medium.
Human biallelic PLPBP impairment → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Indexed abstract; full-text discussion of cultured patient fibroblasts
experimental_model
Patient fibroblasts and biochemical studies in vitamin-B6-dependent epilepsy.
exposure
Patient cells cultured in normal medium containing serum and pyridoxine.
limitations
Later different cultures showed lower PLP; bulk PLP is not enzyme-specific cofactor availability.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A cellular handling defect can raise the measured PLP pool.
primary_references
[darin2016] Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-Dependent Epilepsy. (2016). https://pubmed.ncbi.nlm.nih.gov/27912044/ DOI: 10.1016/j.ajhg.2016.10.011
tissue_or_cell_type
Patient skin fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 413–424
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts and biochemical studies in vitamin-B6-dependent epilepsy. · source_derived_draft · unverified_draft
### b6-transport-plpbp-fibroblast-accumulation PLPBP-deficient patient fibroblasts in Darin 2016 accumulated approximately two- to threefold more PLP than controls in the tested culture medium. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cellular handling defect can raise the measured PLP pool. organism: Homo sapiens tissue_or_cell_type: Patient skin fibroblasts experimental_model: Patient fibroblasts and biochemical studies in vitamin-B6-dependent epilepsy. limitations: Later different cultures showed lower PLP; bulk PLP is not enzyme-specific cofactor availability. exposure: Patient cells cultured in normal medium containing serum and pyridoxine. evidence_location: Indexed abstract; full-text discussion of cultured patient fibroblasts [darin2016] Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-Dependent Epilepsy. (2016). https://pubmed.ncbi.nlm.nih.gov/27912044/ DOI: 10.1016/j.ajhg.2016.10.011
Complete structured claim and evidence
In the 2023 study, PLP was lower in PLPBP-deficient fibroblasts and HEK293 cells after 96 hours with 20 micromolar PN, PM or PL.
Human PLPBP knockout genotype → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 2A-B; Discussion
experimental_model
Human patient skin fibroblasts and CRISPR PLPBP-null HEK293 cells.
exposure
20 micromolar individual vitamer for 96 h.
limitations
Different conditions may explain the earlier accumulation result.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The pool response depended on the cell model and culture conditions.
primary_references
[ciapaite2023] Maintenance of cellular vitamin B6 levels and mitochondrial oxidative function depend on pyridoxal 5'-phosphate homeostasis protein. (2023). https://pubmed.ncbi.nlm.nih.gov/37451483/ DOI: 10.1016/j.jbc.2023.105047
tissue_or_cell_type
Skin fibroblasts and HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 426–437
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human patient skin fibroblasts and CRISPR PLPBP-null HEK293 cells. · source_derived_draft · unverified_draft
### b6-transport-plpbp-low-plp In the 2023 study, PLP was lower in PLPBP-deficient fibroblasts and HEK293 cells after 96 hours with 20 micromolar PN, PM or PL. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pool response depended on the cell model and culture conditions. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts and HEK293 cells experimental_model: Human patient skin fibroblasts and CRISPR PLPBP-null HEK293 cells. limitations: Different conditions may explain the earlier accumulation result. exposure: 20 micromolar individual vitamer for 96 h. evidence_location: Figure 2A-B; Discussion [ciapaite2023] Maintenance of cellular vitamin B6 levels and mitochondrial oxidative function depend on pyridoxal 5'-phosphate homeostasis protein. (2023). https://pubmed.ncbi.nlm.nih.gov/37451483/ DOI: 10.1016/j.jbc.2023.105047
Complete structured claim and evidence
Forty-eight-hour PDXP siRNA restored PLP toward control concentrations in PLPBP-deficient HEK293 cells and decreased PL.
Human PDXP knockdown → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 6B-C
experimental_model
Human patient skin fibroblasts and CRISPR PLPBP-null HEK293 cells.
exposure
15 nM siRNA; 48 h; standard PN-containing medium.
limitations
Cell experiment; does not prove a direct PLPBP-PDXP interaction.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Reducing breakdown restored the cellular PLP pool.
primary_references
[ciapaite2023] Maintenance of cellular vitamin B6 levels and mitochondrial oxidative function depend on pyridoxal 5'-phosphate homeostasis protein. (2023). https://pubmed.ncbi.nlm.nih.gov/37451483/ DOI: 10.1016/j.jbc.2023.105047
tissue_or_cell_type
HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 439–450
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human patient skin fibroblasts and CRISPR PLPBP-null HEK293 cells. · source_derived_draft · unverified_draft
### b6-transport-pdxp-silencing-plpbp-null Forty-eight-hour PDXP siRNA restored PLP toward control concentrations in PLPBP-deficient HEK293 cells and decreased PL. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing breakdown restored the cellular PLP pool. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Human patient skin fibroblasts and CRISPR PLPBP-null HEK293 cells. limitations: Cell experiment; does not prove a direct PLPBP-PDXP interaction. exposure: 15 nM siRNA; 48 h; standard PN-containing medium. evidence_location: Figure 6B-C [ciapaite2023] Maintenance of cellular vitamin B6 levels and mitochondrial oxidative function depend on pyridoxal 5'-phosphate homeostasis protein. (2023). https://pubmed.ncbi.nlm.nih.gov/37451483/ DOI: 10.1016/j.jbc.2023.105047
Complete structured claim and evidence
At 10 nM extracellular PN, SLC25A38-null K562 mitochondria had about 3.9-fold lower PLP despite no whole-cell depletion.
Human SLC25A38 knockout genotype → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Supplementary Figure 3E-F
experimental_model
Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.
exposure
10 nM PN culture condition.
limitations
Not proof that SLC25A38 directly transports PLP.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A normal whole-cell pool can hide mitochondrial depletion.
primary_references
[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3
tissue_or_cell_type
K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 452–463
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. · source_derived_draft · unverified_draft
### b6-transport-slc25a38-pools At 10 nM extracellular PN, SLC25A38-null K562 mitochondria had about 3.9-fold lower PLP despite no whole-cell depletion. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal whole-cell pool can hide mitochondrial depletion. organism: Homo sapiens tissue_or_cell_type: K562 cells experimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. limitations: Not proof that SLC25A38 directly transports PLP. exposure: 10 nM PN culture condition. evidence_location: Supplementary Figure 3E-F [pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3
Complete structured claim and evidence
After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria.
Human SLC25A38 knockout genotype → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 4A-B
experimental_model
Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.
exposure
100 nM D3-PN, one-hour tracing after 10 nM PN conditioning.
limitations
Import, retention and indirect regulation remain alternatives.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Synthesis persisted while mitochondrial accumulation failed.
primary_references
[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3
tissue_or_cell_type
K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 465–476
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. · source_derived_draft · unverified_draft
### b6-transport-slc25a38-tracer After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Synthesis persisted while mitochondrial accumulation failed. organism: Homo sapiens tissue_or_cell_type: K562 cells experimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. limitations: Import, retention and indirect regulation remain alternatives. exposure: 100 nM D3-PN, one-hour tracing after 10 nM PN conditioning. evidence_location: Figure 4A-B [pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3
Complete structured claim and evidence
R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back.
Human SLC25A38 Arg134Cys → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figures 3F and 4C-D
experimental_model
Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.
exposure
Variant versus wild-type expression.
limitations
No direct PLP transport conclusion.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A disease-associated variant failed the cellular rescue test.
primary_references
[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3
tissue_or_cell_type
K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 478–489
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. · source_derived_draft · unverified_draft
### b6-transport-slc25a38-r134c R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A disease-associated variant failed the cellular rescue test. organism: Homo sapiens tissue_or_cell_type: K562 cells experimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. limitations: No direct PLP transport conclusion. exposure: Variant versus wild-type expression. evidence_location: Figures 3F and 4C-D [pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3
Complete structured claim and evidence
Partially purified rat tissue NAD-dependent aldehyde-dehydrogenase activity oxidized PL to 4-pyridoxic acid; oxidase-null rats still excreted the acid.
Rat NAD-dependent pyridoxal dehydrogenase activity → 4-Pyridoxic acid source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
NAD links niacin-derived redox chemistry to B6 catabolism in this rat assay.
evidence_location
Indexed abstract: partially purified rat enzyme and urinary metabolites
experimental_model
Rat tissue enzyme fractions and aldehyde-oxidase activity variants.
exposure
Partially purified activity; kinetic assays at pH 9.6.
limitations
Molecular isoenzyme and quantitative contribution in humans not established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
Rat B6 breakdown had an alternative to aldehyde oxidase.
primary_references
[stanulovic1976] New pathway of conversion of pyridoxal to 4-pyridoxic acid. (1976). https://pubmed.ncbi.nlm.nih.gov/939227/ DOI: 10.1159/000458879
tissue_or_cell_type
Rat tissue enzyme fractions and urine
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 491–503
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat tissue enzyme fractions and aldehyde-oxidase activity variants. · source_derived_draft · unverified_draft
### b6-transport-rat-pl-catabolism Partially purified rat tissue NAD-dependent aldehyde-dehydrogenase activity oxidized PL to 4-pyridoxic acid; oxidase-null rats still excreted the acid. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Rat B6 breakdown had an alternative to aldehyde oxidase. organism: Rattus norvegicus tissue_or_cell_type: Rat tissue enzyme fractions and urine experimental_model: Rat tissue enzyme fractions and aldehyde-oxidase activity variants. limitations: Molecular isoenzyme and quantitative contribution in humans not established. exposure: Partially purified activity; kinetic assays at pH 9.6. evidence_location: Indexed abstract: partially purified rat enzyme and urinary metabolites cross_nutrient: NAD links niacin-derived redox chemistry to B6 catabolism in this rat assay. [stanulovic1976] New pathway of conversion of pyridoxal to 4-pyridoxic acid. (1976). https://pubmed.ncbi.nlm.nih.gov/939227/ DOI: 10.1159/000458879
Complete structured claim and evidence
The human CBS catalytic core binds PLP through its active-site lysine; this site is separate from the heme-binding region.
PLP → Human cystathionine beta-synthase / CBS source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin B6 and sulfur amino-acid metabolism.
experimental_model
Recombinant truncated human CBS crystallography
limitations
The crystallized human construct lacks the C-terminal regulatory region.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
CBS uses active vitamin B6 in its catalytic site.
primary_references
[b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 505–515
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant truncated human CBS crystallography · source_derived_draft · unverified_draft
### b6-met-cbs-plp The human CBS catalytic core binds PLP through its active-site lysine; this site is separate from the heme-binding region. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CBS uses active vitamin B6 in its catalytic site. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: The crystallized human construct lacks the C-terminal regulatory region. cross_nutrient: Vitamin B6 and sulfur amino-acid metabolism. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
Complete structured claim and evidence
PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine.
Human cystathionine beta-synthase / CBS → Cystathionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Methionine-derived sulfur enters cysteine synthesis.
experimental_model
Recombinant truncated human CBS crystallography
limitations
Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency.
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 channels homocysteine into transsulfuration.
primary_references
[b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant truncated human CBS crystallography · source_derived_draft · unverified_draft
### b6-met-cbs-condensation PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine. 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 channels homocysteine into transsulfuration. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency. cross_nutrient: Methionine-derived sulfur enters cysteine synthesis. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
Complete structured claim and evidence
The human CBS structure resolves a heme-binding region distinct from the PLP catalytic site.
Heme → Human cystathionine beta-synthase / CBS source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6 and iron-containing heme meet in one enzyme.
experimental_model
Recombinant truncated human CBS crystallography
limitations
Heme binding does not establish iron supplementation as a way to increase CBS flux.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
CBS contains both heme and active vitamin B6.
primary_references
[b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 529–539
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant truncated human CBS crystallography · source_derived_draft · unverified_draft
### b6-met-cbs-heme The human CBS structure resolves a heme-binding region distinct from the PLP catalytic site. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CBS contains both heme and active vitamin B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: Heme binding does not establish iron supplementation as a way to increase CBS flux. cross_nutrient: B6 and iron-containing heme meet in one enzyme. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
Complete structured claim and evidence
PLP binds human CTH at Lys212 in an active site assembled from adjacent subunits.
PLP → Human cystathionine gamma-lyase / CTH source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Second PLP-dependent step of sulfur amino-acid transsulfuration.
evidence_location
Apo, PLP and PLP-PAG structural comparisons
experimental_model
Purified human CTH apo/holo crystal structures and assays
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
CTH needs an assembled B6-binding catalytic site.
primary_references
[b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 541–552
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CTH apo/holo crystal structures and assays · source_derived_draft · unverified_draft
### b6-met-cth-plp PLP binds human CTH at Lys212 in an active site assembled from adjacent subunits. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CTH needs an assembled B6-binding catalytic site. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human CTH apo/holo crystal structures and assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Second PLP-dependent step of sulfur amino-acid transsulfuration. evidence_location: Apo, PLP and PLP-PAG structural comparisons [b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
Complete structured claim and evidence
Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction.
Human cystathionine gamma-lyase / CTH → Cystathionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes.
experimental_model
Purified human CTH apo/holo crystal structures and assays
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This step releases cysteine for downstream metabolism.
primary_references
[b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 554–564
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CTH apo/holo crystal structures and assays · source_derived_draft · unverified_draft
### b6-met-cth-cleavage Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This step releases cysteine for downstream metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human CTH apo/holo crystal structures and assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes. [b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
Complete structured claim and evidence
Expressed human CTH Thr67Ile had 13% of wild-type catalytic activity in the 2009 study.
Human CTH Thr67Ile variant → Human cystathionine gamma-lyase / CTH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human families; expressed human CTH variants
limitations
Recombinant assay result; not proof of a universal clinical syndrome.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This inherited enzyme change reduces catalytic capacity.
primary_references
[b6-cth-2009] Cystathionine gamma-lyase: Clinical, metabolic, genetic, and structural studies. (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2752209/ DOI: 10.1016/j.ymgme.2009.04.001
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 566–575
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human families; expressed human CTH variants · source_derived_draft · unverified_draft
### b6-met-cth-t67i-activity Expressed human CTH Thr67Ile had 13% of wild-type catalytic activity in the 2009 study. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inherited enzyme change reduces catalytic capacity. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human families; expressed human CTH variants limitations: Recombinant assay result; not proof of a universal clinical syndrome. [b6-cth-2009] Cystathionine gamma-lyase: Clinical, metabolic, genetic, and structural studies. (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2752209/ DOI: 10.1016/j.ymgme.2009.04.001
Complete structured claim and evidence
Vitamin B6 administration lowered plasma cystathionine in the reported CTH Thr67Ile homozygote.
Vitamin B6 → Plasma cystathionine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
p.Thr67Ile section; Supplemental Table 3
experimental_model
Human families; expressed human CTH variants
exposure
Vitamin B6 administration reported for patient 2927; observational case context
limitations
Single genotype-specific case; not a treatment recommendation or evidence of deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6 responsiveness occurred in this particular enzyme genotype.
primary_references
[b6-cth-2009] Cystathionine gamma-lyase: Clinical, metabolic, genetic, and structural studies. (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2752209/ DOI: 10.1016/j.ymgme.2009.04.001
tissue_or_cell_type
Human plasma
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 577–588
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human families; expressed human CTH variants · source_derived_draft · unverified_draft
### b6-met-cth-t67i-clinical Vitamin B6 administration lowered plasma cystathionine in the reported CTH Thr67Ile homozygote. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 responsiveness occurred in this particular enzyme genotype. organism: Homo sapiens tissue_or_cell_type: Human plasma experimental_model: Human families; expressed human CTH variants limitations: Single genotype-specific case; not a treatment recommendation or evidence of deficiency. exposure: Vitamin B6 administration reported for patient 2927; observational case context evidence_location: p.Thr67Ile section; Supplemental Table 3 [b6-cth-2009] Cystathionine gamma-lyase: Clinical, metabolic, genetic, and structural studies. (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2752209/ DOI: 10.1016/j.ymgme.2009.04.001
Complete structured claim and evidence
Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool.
Homocysteine → GSH source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione.
experimental_model
Cultured human hepatoma cell line; metabolic sulfur tracing
limitations
Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione.
primary_references
[b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w
tissue_or_cell_type
Cultured human hepatoma cell line
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 590–600
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human hepatoma cell line; metabolic sulfur tracing · source_derived_draft · unverified_draft
### b6-met-transsulfuration-glutathione Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione. organism: Homo sapiens tissue_or_cell_type: Cultured human hepatoma cell line experimental_model: Cultured human hepatoma cell line; metabolic sulfur tracing limitations: Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion. cross_nutrient: B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione. [b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w
Complete structured claim and evidence
Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT1 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP (B6) and THF (folate) cooperate in one reaction.
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Reaction is reversible; assembly assays do not establish flux in every cell.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–612
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt1-onecarbon Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT2 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP (B6) and THF (folate) cooperate in one reaction.
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Reaction is reversible; assembly assays do not establish flux in every cell.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 614–624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt2-onecarbon Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Adding PLP shifted purified human SHMT2 from dimers toward tetramers.
PLP → SHMT2 tetramer assembly source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
In-vitro cofactor titration; no dietary deficiency threshold was tested.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Active B6 also helps assemble SHMT2.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 626–635
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt2-assembly Adding PLP shifted purified human SHMT2 from dimers toward tetramers. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active B6 also helps assemble SHMT2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: In-vitro cofactor titration; no dietary deficiency threshold was tested. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Human SHMT1 remained tetrameric with and without PLP in the tested solution conditions.
PLP → SHMT1 tetramer assembly source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Tetramer persistence does not mean cofactor-free SHMT1 can perform normal catalysis.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
SHMT1 assembly responds differently from SHMT2.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 637–646
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt1-assembly Human SHMT1 remained tetrameric with and without PLP in the tested solution conditions. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: SHMT1 assembly responds differently from SHMT2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Tetramer persistence does not mean cofactor-free SHMT1 can perform normal catalysis. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Purified chicken glycine decarboxylase contained approximately one PLP molecule per subunit.
PLP → Chicken glycine decarboxylase source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified chicken liver mitochondrial P-protein
limitations
Chicken enzyme; not a direct assay of human GLDC.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Gallus gallus
plain_language
This avian glycine-cleaving enzyme carries active B6.
primary_references
[b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5
tissue_or_cell_type
Chicken liver mitochondrial protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 648–657
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chicken liver mitochondrial P-protein · source_derived_draft · unverified_draft
### b6-met-chicken-gldc-plp Purified chicken glycine decarboxylase contained approximately one PLP molecule per subunit. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This avian glycine-cleaving enzyme carries active B6. organism: Gallus gallus tissue_or_cell_type: Chicken liver mitochondrial protein experimental_model: Purified chicken liver mitochondrial P-protein limitations: Chicken enzyme; not a direct assay of human GLDC. [b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5
Complete structured claim and evidence
Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold.
Chicken glycine decarboxylase → Glycine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP chemistry connects with the lipoyl component of glycine cleavage.
experimental_model
Purified chicken liver mitochondrial P-protein
limitations
Free lipoic acid assay; not evidence that supplements replace the intact cleavage system.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Gallus gallus
plain_language
B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners.
primary_references
[b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5
tissue_or_cell_type
Chicken liver mitochondrial protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 659–669
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chicken liver mitochondrial P-protein · source_derived_draft · unverified_draft
### b6-met-chicken-gldc-decarboxylation Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners. organism: Gallus gallus tissue_or_cell_type: Chicken liver mitochondrial protein experimental_model: Purified chicken liver mitochondrial P-protein limitations: Free lipoic acid assay; not evidence that supplements replace the intact cleavage system. cross_nutrient: PLP chemistry connects with the lipoyl component of glycine cleavage. [b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5
Complete structured claim and evidence
Human GLDC cDNA sequencing identified a conserved PLP-binding lysine region corresponding to the chicken enzyme.
Human glycine decarboxylase / GLDC → PLP source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human and chicken cDNA cloning and sequence comparison
limitations
Sequence evidence; human catalytic rates were not established by this cloning study.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The human enzyme retains the conserved B6-binding machinery.
primary_references
[b6-gldc-1991] The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures. (1991). https://pubmed.ncbi.nlm.nih.gov/1993704/ DOI: 10.1016/s0021-9258(18)49991-7
tissue_or_cell_type
Cloned human GLDC cDNA and deduced protein sequence
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 671–680
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and chicken cDNA cloning and sequence comparison · source_derived_draft · unverified_draft
### b6-met-human-gldc-plp-site Human GLDC cDNA sequencing identified a conserved PLP-binding lysine region corresponding to the chicken enzyme. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human enzyme retains the conserved B6-binding machinery. organism: Homo sapiens tissue_or_cell_type: Cloned human GLDC cDNA and deduced protein sequence experimental_model: Human and chicken cDNA cloning and sequence comparison limitations: Sequence evidence; human catalytic rates were not established by this cloning study. [b6-gldc-1991] The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures. (1991). https://pubmed.ncbi.nlm.nih.gov/1993704/ DOI: 10.1016/s0021-9258(18)49991-7
Complete structured claim and evidence
Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein.
Human aminomethyltransferase / glycine-cleavage T-protein → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry.
experimental_model
Purified human AMT structures and mutational analyses
limitations
AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step.
primary_references
[b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 682–692
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human AMT structures and mutational analyses · source_derived_draft · unverified_draft
### b6-met-amt-onecarbon Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human AMT structures and mutational analyses limitations: AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux. cross_nutrient: B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry. [b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
Complete structured claim and evidence
Human BCAT2 crystal structures show PLP covalently linked to the active-site lysine in active enzyme forms.
PLP → Human mitochondrial branched-chain aminotransferase / BCAT2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6 participates in essential branched-chain amino-acid metabolism.
experimental_model
Purified recombinant human BCAT2 crystallography
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Mitochondrial branched-chain amino-acid metabolism uses bound active B6.
primary_references
[b6-bcat2-2001] The structure of human mitochondrial branched-chain aminotransferase (2001). https://doi.org/10.1107/S0907444901001925 DOI: 10.1107/S0907444901001925
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 694–704
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human BCAT2 crystallography · source_derived_draft · unverified_draft
### b6-met-bcat2-plp Human BCAT2 crystal structures show PLP covalently linked to the active-site lysine in active enzyme forms. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial branched-chain amino-acid metabolism uses bound active B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human BCAT2 crystallography limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6 participates in essential branched-chain amino-acid metabolism. [b6-bcat2-2001] The structure of human mitochondrial branched-chain aminotransferase (2001). https://doi.org/10.1107/S0907444901001925 DOI: 10.1107/S0907444901001925
Complete structured claim and evidence
Human BCAT2 structures capture the isoleucine ketimine and PMP forms of its amino-transfer cycle.
Human mitochondrial branched-chain aminotransferase / BCAT2 → Pyridoxamine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human BCAT2 reaction-intermediate crystallography
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The cofactor cycles between PLP and PMP as it carries an amino group.
primary_references
[b6-bcat2-2002] Crystal structures of human mitochondrial branched chain aminotransferase reaction intermediates: ketimine and pyridoxamine phosphate forms (2002). https://pubmed.ncbi.nlm.nih.gov/12269802/ DOI: 10.1021/bi020221c
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 706–715
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human BCAT2 reaction-intermediate crystallography · source_derived_draft · unverified_draft
### b6-met-bcat2-pmp Human BCAT2 structures capture the isoleucine ketimine and PMP forms of its amino-transfer cycle. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor cycles between PLP and PMP as it carries an amino group. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human BCAT2 reaction-intermediate crystallography limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. [b6-bcat2-2002] Crystal structures of human mitochondrial branched chain aminotransferase reaction intermediates: ketimine and pyridoxamine phosphate forms (2002). https://pubmed.ncbi.nlm.nih.gov/12269802/ DOI: 10.1021/bi020221c
Complete structured claim and evidence
Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.
Human cytosolic branched-chain aminotransferase / BCAT1 → L-Leucine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions.
experimental_model
Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate.
primary_references
[b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures · source_derived_draft · unverified_draft
### b6-met-bcat1-leucine Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions. [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
Complete structured claim and evidence
Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.
Human mitochondrial branched-chain aminotransferase / BCAT2 → L-Leucine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions.
experimental_model
Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate.
primary_references
[b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 729–739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures · source_derived_draft · unverified_draft
### b6-met-bcat2-leucine Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions. [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
Complete structured claim and evidence
Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate.
Human cytosolic aspartate aminotransferase / GOT1 → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human cytosolic GOT1 and GPT; coupled kinetic assays
exposure
Kinetic assays at pH 7.4 and 37 C
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
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 enzyme links amino-acid and carbon metabolism.
primary_references
[b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 741–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic GOT1 and GPT; coupled kinetic assays · source_derived_draft · unverified_draft
### b6-met-got1-reaction Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent enzyme links amino-acid and carbon metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human cytosolic GOT1 and GPT; coupled kinetic assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. exposure: Kinetic assays at pH 7.4 and 37 C [b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
Complete structured claim and evidence
Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate.
Human cytosolic alanine aminotransferase / GPT → L-Alanine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human cytosolic GOT1 and GPT; coupled kinetic assays
exposure
Kinetic assays at pH 7.4 and 37 C
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6-dependent alanine transamination links nitrogen transfer to pyruvate metabolism.
primary_references
[b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 753–763
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic GOT1 and GPT; coupled kinetic assays · source_derived_draft · unverified_draft
### b6-met-gpt-reaction Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent alanine transamination links nitrogen transfer to pyruvate metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human cytosolic GOT1 and GPT; coupled kinetic assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. exposure: Kinetic assays at pH 7.4 and 37 C [b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
Complete structured claim and evidence
Cryo-EM of human liver mitochondria resolved PLP in GOT2, with residues from both subunits forming its binding pocket.
PLP → Human mitochondrial aspartate aminotransferase / GOT2 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human liver mitochondrial lysate cryo-EM
limitations
Structure demonstrates binding; it does not measure the response to B6 restriction.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The mitochondrial aspartate enzyme also has a B6-binding catalytic site.
primary_references
[b6-got2-2023] High-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology. (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10709515/ DOI: 10.1016/j.mcpro.2023.100666
tissue_or_cell_type
Human liver mitochondrial lysate
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 765–774
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver mitochondrial lysate cryo-EM · source_derived_draft · unverified_draft
### b6-met-got2-plp Cryo-EM of human liver mitochondria resolved PLP in GOT2, with residues from both subunits forming its binding pocket. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial aspartate enzyme also has a B6-binding catalytic site. organism: Homo sapiens tissue_or_cell_type: Human liver mitochondrial lysate experimental_model: Human liver mitochondrial lysate cryo-EM limitations: Structure demonstrates binding; it does not measure the response to B6 restriction. [b6-got2-2023] High-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology. (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10709515/ DOI: 10.1016/j.mcpro.2023.100666
Complete structured claim and evidence
Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT.
Human mitochondrial alanine aminotransferase / GPT2 → L-Alanine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GPT2 expressed in E. coli
limitations
Functional-expression evidence; this study did not quantify B6-deficiency sensitivity.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Human alanine metabolism has a separately encoded second enzyme.
primary_references
[b6-gpt2-2002] cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase (2002). https://pubmed.ncbi.nlm.nih.gov/11863375/ DOI: 10.1006/geno.2002.6722
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 776–785
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GPT2 expressed in E. coli · source_derived_draft · unverified_draft
### b6-met-gpt2-reaction Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human alanine metabolism has a separately encoded second enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human GPT2 expressed in E. coli limitations: Functional-expression evidence; this study did not quantify B6-deficiency sensitivity. [b6-gpt2-2002] cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase (2002). https://pubmed.ncbi.nlm.nih.gov/11863375/ DOI: 10.1006/geno.2002.6722
Complete structured claim and evidence
The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391.
PLP → Human erythroid aminolevulinate synthase 2 / ALAS2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent production of precursors for iron-containing heme.
experimental_model
Purified recombinant human ALAS2; crystallography and kinetics
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Active B6 is bound inside the erythroid heme-precursor enzyme.
primary_references
[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 787–797
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft
### b6-met-alas2-plp The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active B6 is bound inside the erythroid heme-precursor enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent production of precursors for iron-containing heme. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
Complete structured claim and evidence
Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide.
Human erythroid aminolevulinate synthase 2 / ALAS2 → 5-Aminolevulinate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6 and glycine support the porphyrin precursor pathway upstream of iron insertion.
experimental_model
Purified recombinant human ALAS2; crystallography and kinetics
limitations
Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction.
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 starts erythroid heme synthesis.
primary_references
[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 799–809
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft
### b6-met-alas2-ala Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide. 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 starts erythroid heme synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction. cross_nutrient: B6 and glycine support the porphyrin precursor pathway upstream of iron insertion. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
Complete structured claim and evidence
ALAS2 Arg452Cys showed reduced PLP affinity and altered succinyl-CoA kinetics despite retained SUCLA2 binding.
Human ALAS2 Arg452Cys variant → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Genetic impairment of a B6-dependent enzyme in an iron/heme disorder.
experimental_model
Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays
limitations
Variant-specific in-vitro kinetics do not predict all clinical responses.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
An inherited heme-synthesis defect can impair B6 cofactor use.
primary_references
[b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 811–821
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays · source_derived_draft · unverified_draft
### b6-met-alas2-r452c ALAS2 Arg452Cys showed reduced PLP affinity and altered succinyl-CoA kinetics despite retained SUCLA2 binding. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited heme-synthesis defect can impair B6 cofactor use. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays limitations: Variant-specific in-vitro kinetics do not predict all clinical responses. cross_nutrient: Genetic impairment of a B6-dependent enzyme in an iron/heme disorder. [b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423
Complete structured claim and evidence
ALAS2 Met567Val retained normal activity in purified assays but showed markedly reduced retention on SUCLA2 affinity columns.
Human ALAS2 Met567Val variant → Human succinyl-CoA synthetase ADP-forming beta subunit / SUCLA2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B6 enzyme function can depend on protein machinery as well as cofactor supply.
experimental_model
Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays
limitations
Normal in-vitro catalysis and defective binding coexist; these are complementary assay results.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Some heme defects involve enzyme partnerships even when a simple enzyme assay looks normal.
primary_references
[b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 823–833
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays · source_derived_draft · unverified_draft
### b6-met-alas2-m567v ALAS2 Met567Val retained normal activity in purified assays but showed markedly reduced retention on SUCLA2 affinity columns. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some heme defects involve enzyme partnerships even when a simple enzyme assay looks normal. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays limitations: Normal in-vitro catalysis and defective binding coexist; these are complementary assay results. cross_nutrient: B6 enzyme function can depend on protein machinery as well as cofactor supply. [b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423
Complete structured claim and evidence
Chenodeoxycholic acid increased ALAS1 mRNA and enzyme activity in primary human hepatocytes and liver slices through an FXR-linked regulatory mechanism.
Chenodeoxycholic acid → Human aminolevulinate synthase 1 / ALAS1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Hepatic heme synthesis; ALAS1 is distinct from erythroid ALAS2.
experimental_model
Primary human hepatocytes and human liver slices; reporter assays
exposure
Experimental bile-acid or FXR-agonist treatment
limitations
No B6 manipulation; this is regulation of the pathway, not proof of a B6 rescue effect.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The liver heme pathway has its own regulation in addition to its cofactor needs.
primary_references
[b6-alas1-2007] Regulation of human liver delta-aminolevulinic acid synthase by bile acids. (2007). https://pubmed.ncbi.nlm.nih.gov/17975826/ DOI: 10.1002/hep.21879
tissue_or_cell_type
Primary human hepatocytes and human liver slices
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 835–846
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human hepatocytes and human liver slices; reporter assays · source_derived_draft · unverified_draft
### b6-met-alas1-fxr Chenodeoxycholic acid increased ALAS1 mRNA and enzyme activity in primary human hepatocytes and liver slices through an FXR-linked regulatory mechanism. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver heme pathway has its own regulation in addition to its cofactor needs. organism: Homo sapiens tissue_or_cell_type: Primary human hepatocytes and human liver slices experimental_model: Primary human hepatocytes and human liver slices; reporter assays limitations: No B6 manipulation; this is regulation of the pathway, not proof of a B6 rescue effect. cross_nutrient: Hepatic heme synthesis; ALAS1 is distinct from erythroid ALAS2. exposure: Experimental bile-acid or FXR-agonist treatment [b6-alas1-2007] Regulation of human liver delta-aminolevulinic acid synthase by bile acids. (2007). https://pubmed.ncbi.nlm.nih.gov/17975826/ DOI: 10.1002/hep.21879
Complete structured claim and evidence
Rabbit muscle phosphorylase crystallography located PLP buried next to the catalytic glucose-binding site.
PLP → Rabbit skeletal-muscle glycogen phosphorylase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-linked glycogen chemistry involves phosphate-containing substrates.
experimental_model
Rabbit skeletal muscle glycogen phosphorylase crystallography
limitations
Rabbit structure; the spatial relationship alone does not establish every catalytic step.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Oryctolagus cuniculus
plain_language
B6 also participates in glycogen metabolism.
primary_references
[b6-phosphorylase-1977] Location of pyridoxal phosphate in glycogen phosphorylase a. (1977). https://pmc.ncbi.nlm.nih.gov/articles/PMC432034/ DOI: 10.1073/pnas.74.11.4757
tissue_or_cell_type
Rabbit skeletal-muscle protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 848–858
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rabbit skeletal muscle glycogen phosphorylase crystallography · source_derived_draft · unverified_draft
### b6-met-rabbit-phosphorylase-plp Rabbit muscle phosphorylase crystallography located PLP buried next to the catalytic glucose-binding site. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 also participates in glycogen metabolism. organism: Oryctolagus cuniculus tissue_or_cell_type: Rabbit skeletal-muscle protein experimental_model: Rabbit skeletal muscle glycogen phosphorylase crystallography limitations: Rabbit structure; the spatial relationship alone does not establish every catalytic step. cross_nutrient: B6-linked glycogen chemistry involves phosphate-containing substrates. [b6-phosphorylase-1977] Location of pyridoxal phosphate in glycogen phosphorylase a. (1977). https://pmc.ncbi.nlm.nih.gov/articles/PMC432034/ DOI: 10.1073/pnas.74.11.4757
Complete structured claim and evidence
A labeled cofactor-analogue experiment supported direct participation of the PLP phosphate group in glycogen phosphorylase glucosyl transfer.
PLP → Rabbit skeletal-muscle glycogen phosphorylase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP-phosphate chemistry supports glycogen metabolism.
experimental_model
Rabbit muscle phosphorylase reconstituted with synthetic cofactor analogue
exposure
Synthetic pyridoxal-diphospho-glucose analogue reconstitution
limitations
Mechanistic analogue evidence; not a demonstration of muscle glycogen failure in human B6 deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Oryctolagus cuniculus
plain_language
The phosphate portion of active B6 helps this carbohydrate reaction.
primary_references
[b6-phosphorylase-1982] Catalytic mechanism of glycogen phosphorylase: pyridoxal(5')diphospho(1)-alpha-D-glucose as a transition-state analogue. (1982). https://pmc.ncbi.nlm.nih.gov/articles/PMC346497/ DOI: 10.1073/pnas.79.12.3716
tissue_or_cell_type
Rabbit skeletal-muscle protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 860–871
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rabbit muscle phosphorylase reconstituted with synthetic cofactor analogue · source_derived_draft · unverified_draft
### b6-met-rabbit-phosphorylase-phosphate A labeled cofactor-analogue experiment supported direct participation of the PLP phosphate group in glycogen phosphorylase glucosyl transfer. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate portion of active B6 helps this carbohydrate reaction. organism: Oryctolagus cuniculus tissue_or_cell_type: Rabbit skeletal-muscle protein experimental_model: Rabbit muscle phosphorylase reconstituted with synthetic cofactor analogue limitations: Mechanistic analogue evidence; not a demonstration of muscle glycogen failure in human B6 deficiency. cross_nutrient: PLP-phosphate chemistry supports glycogen metabolism. exposure: Synthetic pyridoxal-diphospho-glucose analogue reconstitution [b6-phosphorylase-1982] Catalytic mechanism of glycogen phosphorylase: pyridoxal(5')diphospho(1)-alpha-D-glucose as a transition-state analogue. (1982). https://pmc.ncbi.nlm.nih.gov/articles/PMC346497/ DOI: 10.1073/pnas.79.12.3716
Complete structured claim and evidence
Human kynureninase crystallography resolves the PLP-containing active-site architecture.
PLP → Human kynureninase / KYNU source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent KYNU acts in the pathway leading from tryptophan toward niacin/NAD precursors.
experimental_model
Recombinant human KYNU crystallography and biochemical characterization
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
KYNU uses active B6 in the tryptophan pathway.
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 873–883
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-plp Human kynureninase crystallography resolves the PLP-containing active-site architecture. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: KYNU uses active B6 in the tryptophan pathway. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human KYNU crystallography and biochemical characterization limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent KYNU acts in the pathway leading from tryptophan toward niacin/NAD precursors. [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
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
Under niacin-free feeding, B6-free rats had lower apparent tryptophan-to-niacin conversion than rats receiving B6.
Vitamin B6 → Apparent tryptophan-to-niacin conversion from urinary metabolites source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Dietary B6 status affected apparent tryptophan-to-niacin conversion.
experimental_model
Young male Wistar rats; four controlled diets for 19 days
exposure
Young male Wistar rats; 19-day diets; conversion contrast within niacin-free groups
limitations
Apparent urinary conversion, not net synthesis or a human requirement.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
B6 shortage reduced this dietary study's estimate of niacin production from tryptophan.
primary_references
[b6-niacin-1995] Effects of Vitamin B6 Deficiency on the Conversion Ratio of Tryptophan to Niacin (1995). https://doi.org/10.1271/bbb.59.2060 DOI: 10.1271/bbb.59.2060
tissue_or_cell_type
Whole-animal dietary intake and urine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 898–909
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Young male Wistar rats; four controlled diets for 19 days · source_derived_draft · unverified_draft
### b6-met-rat-niacin-conversion Under niacin-free feeding, B6-free rats had lower apparent tryptophan-to-niacin conversion than rats receiving B6. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 shortage reduced this dietary study's estimate of niacin production from tryptophan. organism: Rattus norvegicus tissue_or_cell_type: Whole-animal dietary intake and urine experimental_model: Young male Wistar rats; four controlled diets for 19 days limitations: Apparent urinary conversion, not net synthesis or a human requirement. cross_nutrient: Dietary B6 status affected apparent tryptophan-to-niacin conversion. exposure: Young male Wistar rats; 19-day diets; conversion contrast within niacin-free groups [b6-niacin-1995] Effects of Vitamin B6 Deficiency on the Conversion Ratio of Tryptophan to Niacin (1995). https://doi.org/10.1271/bbb.59.2060 DOI: 10.1271/bbb.59.2060
Complete structured claim and evidence
Both B6-free rat diet groups showed substantially increased urinary xanthurenate relative to B6-containing groups.
Vitamin B6 → Urinary xanthurenate excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6 and tryptophan metabolism.
experimental_model
Young male Wistar rats; four controlled diets for 19 days
exposure
19-day controlled diets
limitations
The marker does not independently measure intracellular NAD.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
B6 withdrawal diverted this urinary tryptophan-metabolism readout.
primary_references
[b6-niacin-1995] Effects of Vitamin B6 Deficiency on the Conversion Ratio of Tryptophan to Niacin (1995). https://doi.org/10.1271/bbb.59.2060 DOI: 10.1271/bbb.59.2060
tissue_or_cell_type
Urine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 911–922
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Young male Wistar rats; four controlled diets for 19 days · source_derived_draft · unverified_draft
### b6-met-rat-xanthurenate Both B6-free rat diet groups showed substantially increased urinary xanthurenate relative to B6-containing groups. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 withdrawal diverted this urinary tryptophan-metabolism readout. organism: Rattus norvegicus tissue_or_cell_type: Urine experimental_model: Young male Wistar rats; four controlled diets for 19 days limitations: The marker does not independently measure intracellular NAD. cross_nutrient: B6 and tryptophan metabolism. exposure: 19-day controlled diets [b6-niacin-1995] Effects of Vitamin B6 Deficiency on the Conversion Ratio of Tryptophan to Niacin (1995). https://doi.org/10.1271/bbb.59.2060 DOI: 10.1271/bbb.59.2060
Complete structured claim and evidence
Human SCLY has two cofactor-containing active sites at its homodimer interface, with both subunits contributing to each site.
SCLY → PLP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent machinery participates in selenium metabolism.
existing_related_claim_ids
["54d5691e-ef60-5f20-a204-abc3fcef9c21", "b6605dbc-466c-5591-965b-0a11b1b3c6fc"]
experimental_model
Recombinant human SCLY; structures and substrate assays
limitations
Structural/biochemical evidence; dietary B6 withdrawal was not tested.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The selenium enzyme has a shared B6-binding architecture.
primary_references
[b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 924–935
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SCLY; structures and substrate assays · source_derived_draft · unverified_draft
### b6-met-scly-structure Human SCLY has two cofactor-containing active sites at its homodimer interface, with both subunits contributing to each site. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The selenium enzyme has a shared B6-binding architecture. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SCLY; structures and substrate assays limitations: Structural/biochemical evidence; dietary B6 withdrawal was not tested. cross_nutrient: B6-dependent machinery participates in selenium metabolism. existing_related_claim_ids: ["54d5691e-ef60-5f20-a204-abc3fcef9c21", "b6605dbc-466c-5591-965b-0a11b1b3c6fc"] [b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581
Complete structured claim and evidence
Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays.
Human SCLY Asp146Lys variant → L-Cysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme.
experimental_model
Recombinant human SCLY; structures and substrate assays
limitations
Engineered gain of function; physiological rates and clinical effects were not tested.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A specific enzyme residue helps distinguish selenium from sulfur substrates.
primary_references
[b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 937–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SCLY; structures and substrate assays · source_derived_draft · unverified_draft
### b6-met-scly-specificity Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific enzyme residue helps distinguish selenium from sulfur substrates. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SCLY; structures and substrate assays limitations: Engineered gain of function; physiological rates and clinical effects were not tested. cross_nutrient: Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme. [b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581
Complete structured claim and evidence
PLP-bound human GAD67 catalyzes glutamate decarboxylation to GABA.
Human glutamate decarboxylase 67 / GAD1 → Gamma-aminobutyric acid source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human GAD isoforms; crystallography and enzyme kinetics
exposure
Glutamate turnover in recombinant enzyme assays.
limitations
Recombinant chemistry does not establish a human supplementation response.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Activated B6 helps this enzyme make GABA.
primary_references
[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 949–959
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics · source_derived_draft · unverified_draft
### b6-neuro-gad1-gaba PLP-bound human GAD67 catalyzes glutamate decarboxylation to GABA. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 helps this enzyme make GABA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics limitations: Recombinant chemistry does not establish a human supplementation response. exposure: Glutamate turnover in recombinant enzyme assays. [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
Complete structured claim and evidence
PLP-bound human GAD65 catalyzes glutamate decarboxylation to GABA.
Human glutamate decarboxylase 65 / GAD2 → Gamma-aminobutyric acid source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human GAD isoforms; crystallography and enzyme kinetics
exposure
Glutamate turnover in recombinant enzyme assays.
limitations
Recombinant chemistry does not establish a human supplementation response.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Activated B6 helps this enzyme make GABA.
primary_references
[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 961–971
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics · source_derived_draft · unverified_draft
### b6-neuro-gad2-gaba PLP-bound human GAD65 catalyzes glutamate decarboxylation to GABA. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 helps this enzyme make GABA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics limitations: Recombinant chemistry does not establish a human supplementation response. exposure: Glutamate turnover in recombinant enzyme assays. [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
Complete structured claim and evidence
GAD65 catalytic-loop mobility favors a side reaction producing succinic semialdehyde and releasing the converted cofactor as PMP.
Human glutamate decarboxylase 65 / GAD2 → Pyridoxamine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human GAD isoforms; crystallography and enzyme kinetics; Human GAD65/GAD67 recombinant chimeras
exposure
Glutamate incubation and enzyme kinetics.
limitations
Loop causality is supported by structure and kinetics; cellular net GABA was not measured.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
GAD65 can switch into an inactive cofactor-free form.
primary_references
[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228 [langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111
revision_history
[{"kind": "draft-correction", "description": "Corrected released cofactor identity from PLP to PMP after checking the source; not a scientific conflict."}]
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 973–985
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics; Human GAD65/GAD67 recombinant chimeras · source_derived_draft · unverified_draft
### b6-neuro-gad65-autoinactivation GAD65 catalytic-loop mobility favors a side reaction producing succinic semialdehyde and releasing the converted cofactor as PMP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: GAD65 can switch into an inactive cofactor-free form. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics; Human GAD65/GAD67 recombinant chimeras limitations: Loop causality is supported by structure and kinetics; cellular net GABA was not measured. exposure: Glutamate incubation and enzyme kinetics. revision_history: [{"kind": "draft-correction", "description": "Corrected released cofactor identity from PLP to PMP after checking the source; not a scientific conflict."}] [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228 [langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111
Complete structured claim and evidence
GAD65/GAD67 chimera experiments implicated the C-terminal domain, together with the catalytic loop, in controlling auto-inactivation.
Human glutamate decarboxylase 65 / GAD2 → PLP source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GAD65/GAD67 recombinant chimeras
exposure
Engineered domain/loop swaps; glutamate-dependent auto-inactivation assays.
limitations
Artificial chimeras; not patient mutations or nutritional deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
More than the active-site loop controls enzyme shutoff.
primary_references
[langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 987–997
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GAD65/GAD67 recombinant chimeras · source_derived_draft · unverified_draft
### b6-neuro-gad-domain-control GAD65/GAD67 chimera experiments implicated the C-terminal domain, together with the catalytic loop, in controlling auto-inactivation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More than the active-site loop controls enzyme shutoff. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human GAD65/GAD67 recombinant chimeras limitations: Artificial chimeras; not patient mutations or nutritional deficiency. exposure: Engineered domain/loop swaps; glutamate-dependent auto-inactivation assays. [langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111
Complete structured claim and evidence
Expressed human DDC decarboxylated L-DOPA; added PLP enhanced the measured activity.
Human aromatic L-amino acid decarboxylase / DDC → Dopamine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human DDC expressed in monkey COS cells; enzyme assays
exposure
PLP addition to transfected COS-cell enzyme incubations.
limitations
An expression-system response is not proof that supplements increase brain monoamines.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Human DDC expressed in monkey COS cells
plain_language
B6 cofactor supports this monoamine-producing step.
primary_references
[sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
tissue_or_cell_type
COS-cell expression system
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 999–1009
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DDC expressed in monkey COS cells; enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-ddc-dopamine Expressed human DDC decarboxylated L-DOPA; added PLP enhanced the measured activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 cofactor supports this monoamine-producing step. organism: Human DDC expressed in monkey COS cells tissue_or_cell_type: COS-cell expression system experimental_model: Human DDC expressed in monkey COS cells; enzyme assays limitations: An expression-system response is not proof that supplements increase brain monoamines. exposure: PLP addition to transfected COS-cell enzyme incubations. [sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
Complete structured claim and evidence
Expressed human DDC decarboxylated 5-hydroxy-L-tryptophan; added PLP enhanced the measured activity.
Human aromatic L-amino acid decarboxylase / DDC → Serotonin source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human DDC expressed in monkey COS cells; enzyme assays
exposure
PLP addition to transfected COS-cell enzyme incubations.
limitations
An expression-system response is not proof that supplements increase brain monoamines.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Human DDC expressed in monkey COS cells
plain_language
B6 cofactor supports this monoamine-producing step.
primary_references
[sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
tissue_or_cell_type
COS-cell expression system
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1011–1021
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DDC expressed in monkey COS cells; enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-ddc-serotonin Expressed human DDC decarboxylated 5-hydroxy-L-tryptophan; added PLP enhanced the measured activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 cofactor supports this monoamine-producing step. organism: Human DDC expressed in monkey COS cells tissue_or_cell_type: COS-cell expression system experimental_model: Human DDC expressed in monkey COS cells; enzyme assays limitations: An expression-system response is not proof that supplements increase brain monoamines. exposure: PLP addition to transfected COS-cell enzyme incubations. [sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
Complete structured claim and evidence
Human apoDDC has exposed active sites; PLP-titrated structures and kinetics support a cofactor-linked conformational transition.
PLP → Human aromatic L-amino acid decarboxylase / DDC source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human DDC crystallography and kinetics
exposure
Apoenzyme crystallization and varied crystal PLP concentrations.
limitations
The closed comparison included pig holoenzyme; proposed degradation consequences were not directly established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Cofactor binding changes the enzyme structure.
primary_references
[giardina-2011-ddc] Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3251144/ DOI: 10.1073/pnas.1111456108
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1023–1033
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human DDC crystallography and kinetics · source_derived_draft · unverified_draft
### b6-neuro-ddc-plp-conformation Human apoDDC has exposed active sites; PLP-titrated structures and kinetics support a cofactor-linked conformational transition. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor binding changes the enzyme structure. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human DDC crystallography and kinetics limitations: The closed comparison included pig holoenzyme; proposed degradation consequences were not directly established. exposure: Apoenzyme crystallization and varied crystal PLP concentrations. [giardina-2011-ddc] Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3251144/ DOI: 10.1073/pnas.1111456108
Complete structured claim and evidence
Human holoDDC crystallography resolved an internal PLP aldimine at 1.9 angstrom resolution.
PLP → Human aromatic L-amino acid decarboxylase / DDC source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human DDC structures, SAXS and molecular dynamics
exposure
Crystallized purified holoenzyme.
limitations
Structure describes a catalytic state, not a dietary dose requirement.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The active B6 cofactor is chemically attached inside DDC.
primary_references
[bisello-2023-ddc] Human aromatic amino acid decarboxylase is an asymmetric and flexible enzyme: Implication in aromatic amino acid decarboxylase deficiency (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10382914/ DOI: 10.1002/pro.4732
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1035–1045
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DDC structures, SAXS and molecular dynamics · source_derived_draft · unverified_draft
### b6-neuro-ddc-internal-aldimine Human holoDDC crystallography resolved an internal PLP aldimine at 1.9 angstrom resolution. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active B6 cofactor is chemically attached inside DDC. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human DDC structures, SAXS and molecular dynamics limitations: Structure describes a catalytic state, not a dietary dose requirement. exposure: Crystallized purified holoenzyme. [bisello-2023-ddc] Human aromatic amino acid decarboxylase is an asymmetric and flexible enzyme: Implication in aromatic amino acid decarboxylase deficiency (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10382914/ DOI: 10.1002/pro.4732
Complete structured claim and evidence
Recombinant human HDC catalyzes PLP-dependent histidine decarboxylation to histamine.
Human histidine decarboxylase / HDC → Histamine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant engineered human HDC; crystallography and enzyme assays
exposure
Recombinant HDC enzyme-activity assays.
limitations
Engineered soluble HDC construct; histamine release and allergy outcomes were not tested.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Activated B6 supports histamine synthesis.
primary_references
[komori-2012-hdc] Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436558/ DOI: 10.1074/jbc.M112.381897
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1047–1057
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant engineered human HDC; crystallography and enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-hdc-histamine Recombinant human HDC catalyzes PLP-dependent histidine decarboxylation to histamine. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 supports histamine synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant engineered human HDC; crystallography and enzyme assays limitations: Engineered soluble HDC construct; histamine release and allergy outcomes were not tested. exposure: Recombinant HDC enzyme-activity assays. [komori-2012-hdc] Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436558/ DOI: 10.1074/jbc.M112.381897
Complete structured claim and evidence
The human HDC inhibitor complex resolved a PLP-histidine-methyl-ester external aldimine in its active site.
Human histidine decarboxylase / HDC → PLP source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant engineered human HDC; crystallography and enzyme assays
exposure
Histidine methyl ester co-crystallization.
limitations
Inhibitor-bound engineered protein; not direct observation of every physiological catalytic intermediate.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The structure shows how HDC holds a B6-bound substrate mimic.
primary_references
[komori-2012-hdc] Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436558/ DOI: 10.1074/jbc.M112.381897
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1059–1069
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant engineered human HDC; crystallography and enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-hdc-external-aldimine The human HDC inhibitor complex resolved a PLP-histidine-methyl-ester external aldimine in its active site. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The structure shows how HDC holds a B6-bound substrate mimic. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant engineered human HDC; crystallography and enzyme assays limitations: Inhibitor-bound engineered protein; not direct observation of every physiological catalytic intermediate. exposure: Histidine methyl ester co-crystallization. [komori-2012-hdc] Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436558/ DOI: 10.1074/jbc.M112.381897
Complete structured claim and evidence
Pig GABA aminotransferase contains a PLP-dependent active site for GABA degradation.
Pig GABA aminotransferase / ABAT → Gamma-aminobutyric acid source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified pig GABA aminotransferase; crystallography
exposure
Purified native pig GABA aminotransferase structure.
limitations
Pig enzyme evidence cannot alone predict human brain GABA responses to B6.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Sus scrofa
plain_language
B6 participates in GABA breakdown as well as synthesis.
primary_references
[storici-1999-gaba-at] Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy (1999). https://iris.uniroma1.it/handle/11573/393739 DOI: 10.1021/bi990478j
tissue_or_cell_type
Purified pig enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1071–1081
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig GABA aminotransferase; crystallography · source_derived_draft · unverified_draft
### b6-neuro-gaba-degradation Pig GABA aminotransferase contains a PLP-dependent active site for GABA degradation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 participates in GABA breakdown as well as synthesis. organism: Sus scrofa tissue_or_cell_type: Purified pig enzyme experimental_model: Purified pig GABA aminotransferase; crystallography limitations: Pig enzyme evidence cannot alone predict human brain GABA responses to B6. exposure: Purified native pig GABA aminotransferase structure. [storici-1999-gaba-at] Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy (1999). https://iris.uniroma1.it/handle/11573/393739 DOI: 10.1021/bi990478j
Complete structured claim and evidence
Native and inhibitor-bound pig liver GABA-AT structures resolved a [2Fe-2S] cluster near the PLP sites.
Pig GABA aminotransferase / ABAT → [2Fe-2S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6 and iron-sulfur cluster coexistence; functional nutritional interaction remains untested.
experimental_model
Pig liver GABA aminotransferase; inhibitor complexes and spectroscopy
exposure
Native and inhibitor-bound enzyme crystallography.
limitations
The cluster function was unknown; no iron-deficiency or B6-rescue response was demonstrated.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Sus scrofa
plain_language
Iron and B6 occur in the same enzyme structure.
primary_references
[storici-2004-gaba-at] Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin (2004). https://doi.org/10.1074/jbc.M305884200 DOI: 10.1074/jbc.M305884200
tissue_or_cell_type
Pig liver enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1083–1094
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig liver GABA aminotransferase; inhibitor complexes and spectroscopy · source_derived_draft · unverified_draft
### b6-neuro-gaba-at-iron-cluster Native and inhibitor-bound pig liver GABA-AT structures resolved a [2Fe-2S] cluster near the PLP sites. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron and B6 occur in the same enzyme structure. organism: Sus scrofa tissue_or_cell_type: Pig liver enzyme experimental_model: Pig liver GABA aminotransferase; inhibitor complexes and spectroscopy limitations: The cluster function was unknown; no iron-deficiency or B6-rescue response was demonstrated. exposure: Native and inhibitor-bound enzyme crystallography. cross_nutrient: B6 and iron-sulfur cluster coexistence; functional nutritional interaction remains untested. [storici-2004-gaba-at] Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin (2004). https://doi.org/10.1074/jbc.M305884200 DOI: 10.1074/jbc.M305884200
Complete structured claim and evidence
Vigabatrin formed a covalent adduct involving pig GABA-AT Lys329 and its PLP cofactor.
Vigabatrin → Pig GABA aminotransferase / ABAT source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Pig liver GABA aminotransferase; inhibitor complexes and spectroscopy
exposure
Inhibitor-treated purified enzyme.
limitations
Does not establish systemic B6 depletion.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Sus scrofa
plain_language
The drug traps the enzyme together with its B6 cofactor.
primary_references
[storici-2004-gaba-at] Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin (2004). https://doi.org/10.1074/jbc.M305884200 DOI: 10.1074/jbc.M305884200
tissue_or_cell_type
Pig liver enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1096–1106
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig liver GABA aminotransferase; inhibitor complexes and spectroscopy · source_derived_draft · unverified_draft
### b6-neuro-vigabatrin-plp-adduct Vigabatrin formed a covalent adduct involving pig GABA-AT Lys329 and its PLP cofactor. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug traps the enzyme together with its B6 cofactor. organism: Sus scrofa tissue_or_cell_type: Pig liver enzyme experimental_model: Pig liver GABA aminotransferase; inhibitor complexes and spectroscopy limitations: Does not establish systemic B6 depletion. exposure: Inhibitor-treated purified enzyme. [storici-2004-gaba-at] Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin (2004). https://doi.org/10.1074/jbc.M305884200 DOI: 10.1074/jbc.M305884200
Complete structured claim and evidence
Human SPT structures place PLP at the SPTLC1-SPTLC2 interface, with the catalytic lysine supplied by SPTLC2.
PLP → Human serine palmitoyltransferase long-chain base subunit 2 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays
exposure
Cryo-EM of recombinant complexes.
limitations
No dietary B6 manipulation.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
SPT uses activated B6 where its two core subunits meet.
primary_references
[wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1108–1118
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays · source_derived_draft · unverified_draft
### b6-neuro-spt-plp-site Human SPT structures place PLP at the SPTLC1-SPTLC2 interface, with the catalytic lysine supplied by SPTLC2. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: SPT uses activated B6 where its two core subunits meet. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays limitations: No dietary B6 manipulation. exposure: Cryo-EM of recombinant complexes. [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
Complete structured claim and evidence
PLP-dependent human SPT condenses serine and palmitoyl-CoA into 3-ketosphinganine; the product-bound structure locates its headgroup and acyl chain.
Human SPTLC1-SPTLC2-SPTSSA complex → 3-Ketosphinganine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent use of the amino acid serine and a fatty-acyl-CoA substrate.
experimental_model
Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays
exposure
Product-bound cryo-EM and functional enzyme assays.
limitations
Does not show that B6 supplementation repairs myelin.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6 supports entry into sphingolipid synthesis.
primary_references
[wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1120–1131
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays · source_derived_draft · unverified_draft
### b6-neuro-spt-sphingolipid-entry PLP-dependent human SPT condenses serine and palmitoyl-CoA into 3-ketosphinganine; the product-bound structure locates its headgroup and acyl chain. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 supports entry into sphingolipid synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays limitations: Does not show that B6 supplementation repairs myelin. exposure: Product-bound cryo-EM and functional enzyme assays. cross_nutrient: B6-dependent use of the amino acid serine and a fatty-acyl-CoA substrate. [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
Complete structured claim and evidence
ORMDL3 restricts access to the substrate tunnel of the PLP-dependent human SPT complex.
Human ORMDL sphingolipid biosynthesis regulator 3 → Human SPTLC1-SPTLC2-SPTSSA complex source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays
exposure
Recombinant complex structures and functional assays.
limitations
Ceramide sensing was proposed; these structures alone do not establish its complete mechanism.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Cofactor availability is only one control on sphingolipid production.
primary_references
[wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1133–1143
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays · source_derived_draft · unverified_draft
### b6-neuro-spt-ormdl-gating ORMDL3 restricts access to the substrate tunnel of the PLP-dependent human SPT complex. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor availability is only one control on sphingolipid production. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays limitations: Ceramide sensing was proposed; these structures alone do not establish its complete mechanism. exposure: Recombinant complex structures and functional assays. [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
Complete structured claim and evidence
ALDH7A1 variants identified in affected children abolished antiquitin activity in the reported functional assays.
Biallelic ALDH7A1 disease genotypes studied by Mills 2006 → Antiquitin / ALDH7A1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Lysine catabolic machinery can impair intracellular B6 availability.
experimental_model
Affected children, expressed human ALDH7A1 variants and metabolite chemistry
exposure
Disease-variant functional expression.
limitations
Applies to the studied variants; not all possible ALDH7A1 alleles.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The inherited defect blocks a lysine-breakdown enzyme.
primary_references
[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
tissue_or_cell_type
Patient-linked expression experiments
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1145–1156
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected children, expressed human ALDH7A1 variants and metabolite chemistry · source_derived_draft · unverified_draft
### b6-neuro-aldh7a1-variants ALDH7A1 variants identified in affected children abolished antiquitin activity in the reported functional assays. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inherited defect blocks a lysine-breakdown enzyme. organism: Homo sapiens tissue_or_cell_type: Patient-linked expression experiments experimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry limitations: Applies to the studied variants; not all possible ALDH7A1 alleles. exposure: Disease-variant functional expression. cross_nutrient: Lysine catabolic machinery can impair intracellular B6 availability. [mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
Complete structured claim and evidence
The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway.
Biallelic ALDH7A1 disease genotypes studied by Mills 2006 → Delta1-piperideine-6-carboxylate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Lysine catabolism generates the metabolite that can sequester PLP.
experimental_model
Affected children, expressed human ALDH7A1 variants and metabolite chemistry
exposure
ALDH7A1-associated disease and metabolite analysis.
limitations
This is inherited pathway failure, not lysine toxicity in healthy people.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A blocked lysine pathway builds up B6-reactive metabolites.
primary_references
[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
tissue_or_cell_type
Patient biological samples and biochemical pathway analysis
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1158–1169
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected children, expressed human ALDH7A1 variants and metabolite chemistry · source_derived_draft · unverified_draft
### b6-neuro-aldh7a1-metabolite-accumulation The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked lysine pathway builds up B6-reactive metabolites. organism: Homo sapiens tissue_or_cell_type: Patient biological samples and biochemical pathway analysis experimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry limitations: This is inherited pathway failure, not lysine toxicity in healthy people. exposure: ALDH7A1-associated disease and metabolite analysis. cross_nutrient: Lysine catabolism generates the metabolite that can sequester PLP. [mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
Complete structured claim and evidence
P6C reacts with PLP to form a Knoevenagel condensation product that inactivates the cofactor.
Delta1-piperideine-6-carboxylate → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Direct lysine-metabolite to vitamin-B6 antagonism.
experimental_model
Affected children, expressed human ALDH7A1 variants and metabolite chemistry
exposure
Biochemical P6C-PLP reaction.
limitations
Direct chemistry supports sequestration; it does not quantify PLP loss in every neuronal compartment.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The accumulated lysine metabolite chemically traps activated B6.
primary_references
[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
tissue_or_cell_type
Cell-free chemistry
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1171–1182
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected children, expressed human ALDH7A1 variants and metabolite chemistry · source_derived_draft · unverified_draft
### b6-neuro-p6c-plp-sequestration P6C reacts with PLP to form a Knoevenagel condensation product that inactivates the cofactor. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The accumulated lysine metabolite chemically traps activated B6. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry experimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry limitations: Direct chemistry supports sequestration; it does not quantify PLP loss in every neuronal compartment. exposure: Biochemical P6C-PLP reaction. cross_nutrient: Direct lysine-metabolite to vitamin-B6 antagonism. [mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
Complete structured claim and evidence
Purified human PDXK converted ginkgotoxin to its 5-prime-phosphate in an ATP-dependent assay.
Pyridoxal kinase / PDXK → Ginkgotoxin / 4-prime-O-methylpyridoxine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified recombinant human PDXK; HPLC and kinetic competition assays
exposure
HPLC product identification at 37 C, pH 6.2.
limitations
Purified-enzyme substrate recognition does not establish a whole-body toxicity threshold.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The toxin can use the B6-activating enzyme.
primary_references
[kastner-2007-ginkgotoxin] The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba (2007). https://doi.org/10.1111/j.1742-4658.2007.05654.x DOI: 10.1111/j.1742-4658.2007.05654.x
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1184–1194
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PDXK; HPLC and kinetic competition assays · source_derived_draft · unverified_draft
### b6-neuro-ginkgotoxin-phosphorylation Purified human PDXK converted ginkgotoxin to its 5-prime-phosphate in an ATP-dependent assay. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The toxin can use the B6-activating enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PDXK; HPLC and kinetic competition assays limitations: Purified-enzyme substrate recognition does not establish a whole-body toxicity threshold. exposure: HPLC product identification at 37 C, pH 6.2. [kastner-2007-ginkgotoxin] The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba (2007). https://doi.org/10.1111/j.1742-4658.2007.05654.x DOI: 10.1111/j.1742-4658.2007.05654.x
Complete structured claim and evidence
Ginkgotoxin competed with pyridoxal and delayed PLP formation by human PDXK; increasing pyridoxal alleviated inhibition.
Ginkgotoxin / 4-prime-O-methylpyridoxine → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Purified recombinant human PDXK; HPLC and kinetic competition assays
exposure
25 micromolar pyridoxal with 12.5-25 micromolar ginkgotoxin in illustrative co-incubations.
limitations
Reported Ki was assay-specific; not a clinical exposure limit.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The toxin competes for the enzyme that activates B6.
primary_references
[kastner-2007-ginkgotoxin] The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba (2007). https://doi.org/10.1111/j.1742-4658.2007.05654.x DOI: 10.1111/j.1742-4658.2007.05654.x
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1196–1206
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PDXK; HPLC and kinetic competition assays · source_derived_draft · unverified_draft
### b6-neuro-ginkgotoxin-plp-competition Ginkgotoxin competed with pyridoxal and delayed PLP formation by human PDXK; increasing pyridoxal alleviated inhibition. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The toxin competes for the enzyme that activates B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PDXK; HPLC and kinetic competition assays limitations: Reported Ki was assay-specific; not a clinical exposure limit. exposure: 25 micromolar pyridoxal with 12.5-25 micromolar ginkgotoxin in illustrative co-incubations. [kastner-2007-ginkgotoxin] The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba (2007). https://doi.org/10.1111/j.1742-4658.2007.05654.x DOI: 10.1111/j.1742-4658.2007.05654.x
Complete structured claim and evidence
Human PDXK crystallography placed ginkgotoxin at the pyridoxal-binding site alongside MgATP.
Ginkgotoxin / 4-prime-O-methylpyridoxine → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Purified human PDXK; crystallography and inhibition kinetics
exposure
2.15 angstrom ternary crystal structure.
limitations
Binding in a purified protein does not establish brain concentrations.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The structure directly locates the competing toxin.
primary_references
[gandhi-2012-pdxk-inhibitors] Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040954 DOI: 10.1371/journal.pone.0040954
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1208–1218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human PDXK; crystallography and inhibition kinetics · source_derived_draft · unverified_draft
### b6-neuro-ginkgotoxin-binding Human PDXK crystallography placed ginkgotoxin at the pyridoxal-binding site alongside MgATP. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The structure directly locates the competing toxin. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human PDXK; crystallography and inhibition kinetics limitations: Binding in a purified protein does not establish brain concentrations. exposure: 2.15 angstrom ternary crystal structure. [gandhi-2012-pdxk-inhibitors] Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040954 DOI: 10.1371/journal.pone.0040954
Complete structured claim and evidence
Theophylline inhibited purified human PDXK, with Ki 50 micromolar, and occupied its vitamin-substrate site.
Theophylline → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Purified human PDXK; crystallography and inhibition kinetics
exposure
Purified-enzyme inhibition series; 2.1 angstrom crystal structure.
limitations
Other preparations yielded different Ki values; this is assay context, not a nutritional threshold.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This drug can interfere with B6 activation in an enzyme assay.
primary_references
[gandhi-2012-pdxk-inhibitors] Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040954 DOI: 10.1371/journal.pone.0040954
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1220–1230
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human PDXK; crystallography and inhibition kinetics · source_derived_draft · unverified_draft
### b6-neuro-theophylline-pdxk Theophylline inhibited purified human PDXK, with Ki 50 micromolar, and occupied its vitamin-substrate site. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This drug can interfere with B6 activation in an enzyme assay. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human PDXK; crystallography and inhibition kinetics limitations: Other preparations yielded different Ki values; this is assay context, not a nutritional threshold. exposure: Purified-enzyme inhibition series; 2.1 angstrom crystal structure. [gandhi-2012-pdxk-inhibitors] Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040954 DOI: 10.1371/journal.pone.0040954
Complete structured claim and evidence
Pyridoxine reduced MTT-measured viability of differentiated SH-SY5Y cells after 24 hours in a concentration-dependent manner.
Pyridoxine → SH-SY5Y cell viability by MTT source_derived_draftungraded
Experimental context and source evidence
experimental_model
Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays
exposure
Pyridoxine 0-5 micromolar for 24 hours.
exposure-class
Experimental excess pyridoxine; not dietary B6 deficiency · Pyridoxine
limitations
Tumor-derived cells and MTT endpoint; no oral-dose conversion or human toxicity threshold.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Added pyridoxine harmed this experimental neuronal cell model.
primary_references
[vrolijk-2017-pn] The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function (2017). https://doi.org/10.1016/j.tiv.2017.07.009 DOI: 10.1016/j.tiv.2017.07.009
tissue_or_cell_type
Differentiated SH-SY5Y neuroblastoma cells
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1232–1243
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-pn-cell-viability Pyridoxine reduced MTT-measured viability of differentiated SH-SY5Y cells after 24 hours in a concentration-dependent manner. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Added pyridoxine harmed this experimental neuronal cell model. organism: Homo sapiens tissue_or_cell_type: Differentiated SH-SY5Y neuroblastoma cells experimental_model: Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays limitations: Tumor-derived cells and MTT endpoint; no oral-dose conversion or human toxicity threshold. exposure: Pyridoxine 0-5 micromolar for 24 hours. exposure-class: Experimental excess pyridoxine; not dietary B6 deficiency [vrolijk-2017-pn] The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function (2017). https://doi.org/10.1016/j.tiv.2017.07.009 DOI: 10.1016/j.tiv.2017.07.009
Complete structured claim and evidence
Pyridoxal, pyridoxamine, PLP and PMP did not reduce viability in the tested 24-hour cell assay.
PLP → SH-SY5Y cell viability by MTT source_derived_draftungraded
Experimental context and source evidence
experimental_model
Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays
exposure
Comparators 0-500 micromolar for 24 hours.
exposure-class
Experimental excess pyridoxine; not dietary B6 deficiency · Pyridoxine
limitations
A negative short-term cell assay proves neither universal safety nor equivalent toxicity.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The tested B6 forms behaved differently in this assay.
primary_references
[vrolijk-2017-pn] The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function (2017). https://doi.org/10.1016/j.tiv.2017.07.009 DOI: 10.1016/j.tiv.2017.07.009
tissue_or_cell_type
SH-SY5Y and CaCo-2 cells
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1245–1256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-pn-vitamer-specificity Pyridoxal, pyridoxamine, PLP and PMP did not reduce viability in the tested 24-hour cell assay. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested B6 forms behaved differently in this assay. organism: Homo sapiens tissue_or_cell_type: SH-SY5Y and CaCo-2 cells experimental_model: Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays limitations: A negative short-term cell assay proves neither universal safety nor equivalent toxicity. exposure: Comparators 0-500 micromolar for 24 hours. exposure-class: Experimental excess pyridoxine; not dietary B6 deficiency [vrolijk-2017-pn] The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function (2017). https://doi.org/10.1016/j.tiv.2017.07.009 DOI: 10.1016/j.tiv.2017.07.009
Complete structured claim and evidence
Pyridoxine inhibited the tested PLP-dependent bacterial tyrosine decarboxylase preparation.
Pyridoxine → Enterococcus faecalis tyrosine decarboxylase source_derived_draftungraded
Experimental context and source evidence
experimental_model
Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays
exposure
5 micromolar pyridoxine; commercial Streptococcus faecalis enzyme (current Enterococcus name).
exposure-class
Experimental excess pyridoxine; not dietary B6 deficiency · Pyridoxine
limitations
Not human GAD, DDC or PDXK; mechanism of human neuropathy remains unresolved.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Enterococcus faecalis (reported as Streptococcus faecalis)
plain_language
Pyridoxine interfered with one isolated B6-dependent enzyme.
primary_references
[vrolijk-2017-pn] The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function (2017). https://doi.org/10.1016/j.tiv.2017.07.009 DOI: 10.1016/j.tiv.2017.07.009
tissue_or_cell_type
Cell-free bacterial enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1258–1269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-pn-enzyme-inhibition Pyridoxine inhibited the tested PLP-dependent bacterial tyrosine decarboxylase preparation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pyridoxine interfered with one isolated B6-dependent enzyme. organism: Enterococcus faecalis (reported as Streptococcus faecalis) tissue_or_cell_type: Cell-free bacterial enzyme experimental_model: Differentiated human SH-SY5Y and CaCo-2 cells; isolated enzyme assays limitations: Not human GAD, DDC or PDXK; mechanism of human neuropathy remains unresolved. exposure: 5 micromolar pyridoxine; commercial Streptococcus faecalis enzyme (current Enterococcus name). exposure-class: Experimental excess pyridoxine; not dietary B6 deficiency [vrolijk-2017-pn] The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function (2017). https://doi.org/10.1016/j.tiv.2017.07.009 DOI: 10.1016/j.tiv.2017.07.009
Complete structured claim and evidence
Isoniazid and pyridoxal formed PIH without cells or enzymes.
Isoniazid → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
experimental_model
Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells
exposure
1 mM reactants in PBS; timed incubations at 4 or 37 C.
limitations
High-concentration cell-free chemistry; not proof of neuronal depletion.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Not applicable; chemical reaction
plain_language
A drug can chemically capture a B6 vitamer.
primary_references
[brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294
tissue_or_cell_type
Cell-free PBS
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1271–1281
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells · source_derived_draft · unverified_draft
### b6-neuro-isoniazid-pl-conjugation Isoniazid and pyridoxal formed PIH without cells or enzymes. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug can chemically capture a B6 vitamer. organism: Not applicable; chemical reaction tissue_or_cell_type: Cell-free PBS experimental_model: Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells limitations: High-concentration cell-free chemistry; not proof of neuronal depletion. exposure: 1 mM reactants in PBS; timed incubations at 4 or 37 C. [brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294
Complete structured claim and evidence
The B6-isoniazid conjugate PIH bound iron in the study chelation assay.
Pyridoxal isonicotinoyl hydrazone → Iron source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Drug-modified B6 chemistry creates an iron-binding molecule.
experimental_model
Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells
exposure
Chrome azurol S assay; biochemical and cell-medium samples.
limitations
This endpoint does not establish nutritional iron deficiency in patients.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Not applicable; chemical reaction
plain_language
The drug-B6 product also interacts with iron.
primary_references
[brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294
tissue_or_cell_type
Cell-free chelation assay
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1283–1294
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells · source_derived_draft · unverified_draft
### b6-neuro-pih-iron-chelation The B6-isoniazid conjugate PIH bound iron in the study chelation assay. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug-B6 product also interacts with iron. organism: Not applicable; chemical reaction tissue_or_cell_type: Cell-free chelation assay experimental_model: Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells limitations: This endpoint does not establish nutritional iron deficiency in patients. exposure: Chrome azurol S assay; biochemical and cell-medium samples. cross_nutrient: Drug-modified B6 chemistry creates an iron-binding molecule. [brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294
Complete structured claim and evidence
PIH treatment lowered FECH protein without lowering FECH mRNA in human liver-cell models.
Pyridoxal isonicotinoyl hydrazone → Human ferrochelatase / FECH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B6-drug conjugation connects to iron-sensitive heme machinery.
experimental_model
Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells
exposure
100 micromolar PIH for 16 hours in the initial HepG2/C3A comparison; 24-hour PIH dose-response assays.
limitations
Direct destruction of the FECH iron-sulfur cluster was not demonstrated.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A drug-B6 conjugate affected a heme-making enzyme.
primary_references
[brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294
tissue_or_cell_type
Primary human hepatocytes and HepG2/C3A cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1296–1307
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells · source_derived_draft · unverified_draft
### b6-neuro-pih-fech-protein PIH treatment lowered FECH protein without lowering FECH mRNA in human liver-cell models. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug-B6 conjugate affected a heme-making enzyme. organism: Homo sapiens tissue_or_cell_type: Primary human hepatocytes and HepG2/C3A cells experimental_model: Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells limitations: Direct destruction of the FECH iron-sulfur cluster was not demonstrated. exposure: 100 micromolar PIH for 16 hours in the initial HepG2/C3A comparison; 24-hour PIH dose-response assays. cross_nutrient: B6-drug conjugation connects to iron-sensitive heme machinery. [brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294
Complete structured claim and evidence
Dietary B6 restriction increased plasma cystathionine by 124% while plasma PLP fell from 55.1 to 22.6 nmol/L.
Vitamin B6 → Cystathionine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.
exposure
Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.
limitations
Pool size alone cannot identify the limiting enzyme or quantify pathway flux.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A pathway intermediate accumulated even though the whole pathway did not simply stop.
primary_references
[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1309–1319
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft
### b6-fasting-cystathionine-pool Dietary B6 restriction increased plasma cystathionine by 124% while plasma PLP fell from 55.1 to 22.6 nmol/L. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pathway intermediate accumulated even though the whole pathway did not simply stop. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Pool size alone cannot identify the limiting enzyme or quantify pathway flux. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
Complete structured claim and evidence
Plasma total glutathione rose 38% during restriction; plasma cysteine, homocysteine and CRP did not significantly change.
Vitamin B6 → Plasma total glutathione concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6-dependent sulfur metabolism connects to glutathione, with blood and cellular pools distinguished.
experimental_model
Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.
exposure
Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.
limitations
Plasma total glutathione is not intracellular reduced GSH, tissue antioxidant capacity or synthesis rate.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This experiment did not find a universal glutathione collapse.
primary_references
[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1321–1332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft
### b6-fasting-total-glutathione Plasma total glutathione rose 38% during restriction; plasma cysteine, homocysteine and CRP did not significantly change. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experiment did not find a universal glutathione collapse. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Plasma total glutathione is not intracellular reduced GSH, tissue antioxidant capacity or synthesis rate. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. cross_nutrient: B6-dependent sulfur metabolism connects to glutathione, with blood and cellular pools distinguished. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
Complete structured claim and evidence
Whole-body cysteine flux and fractional cystathionine synthesis were unchanged; transsulfuration-derived cysteine synthesis was below detection in this fasting protocol.
Vitamin B6 → Whole-body cysteine flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.
exposure
Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.
limitations
Below detection is not zero flux, nor proof that transsulfuration was unchanged.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The investigators could measure cysteine turnover but could not reliably quantify one specific input route.
primary_references
[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1334–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft
### b6-fasting-cysteine-flux Whole-body cysteine flux and fractional cystathionine synthesis were unchanged; transsulfuration-derived cysteine synthesis was below detection in this fasting protocol. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The investigators could measure cysteine turnover but could not reliably quantify one specific input route. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Below detection is not zero flux, nor proof that transsulfuration was unchanged. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
Complete structured claim and evidence
Mean postprandial homocysteine remethylation did not significantly change after restriction, with substantial individual variation.
Vitamin B6 → Homocysteine remethylation flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6 intersects methionine/folate metabolism; this experiment does not establish B12 or folate depletion.
experimental_model
Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics.
exposure
28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L.
limitations
Null group means do not establish identical responses or preserved DNA methylation in every tissue.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Lower B6 did not make this measured process uniformly fail.
primary_references
[b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1346–1357
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. · source_derived_draft · unverified_draft
### b6-fed-remethylation-preserved Mean postprandial homocysteine remethylation did not significantly change after restriction, with substantial individual variation. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower B6 did not make this measured process uniformly fail. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. limitations: Null group means do not establish identical responses or preserved DNA methylation in every tissue. exposure: 28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L. cross_nutrient: B6 intersects methionine/folate metabolism; this experiment does not establish B12 or folate depletion. [b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
Complete structured claim and evidence
Mean postprandial transmethylation did not significantly change after restriction, with substantial individual variation.
Vitamin B6 → Methionine-cycle transmethylation flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6 intersects methionine/folate metabolism; this experiment does not establish B12 or folate depletion.
experimental_model
Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics.
exposure
28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L.
limitations
Null group means do not establish identical responses or preserved DNA methylation in every tissue.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Lower B6 did not make this measured process uniformly fail.
primary_references
[b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1359–1370
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. · source_derived_draft · unverified_draft
### b6-fed-transmethylation-preserved Mean postprandial transmethylation did not significantly change after restriction, with substantial individual variation. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower B6 did not make this measured process uniformly fail. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. limitations: Null group means do not establish identical responses or preserved DNA methylation in every tissue. exposure: 28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L. cross_nutrient: B6 intersects methionine/folate metabolism; this experiment does not establish B12 or folate depletion. [b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
Complete structured claim and evidence
Mean postprandial total transsulfuration did not significantly change after restriction, with substantial individual variation.
Vitamin B6 → Total transsulfuration flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6 intersects methionine/folate metabolism; this experiment does not establish B12 or folate depletion.
experimental_model
Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics.
exposure
28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L.
limitations
Null group means do not establish identical responses or preserved DNA methylation in every tissue.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Lower B6 did not make this measured process uniformly fail.
primary_references
[b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1372–1383
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. · source_derived_draft · unverified_draft
### b6-fed-transsulfuration-preserved Mean postprandial total transsulfuration did not significantly change after restriction, with substantial individual variation. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower B6 did not make this measured process uniformly fail. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. limitations: Null group means do not establish identical responses or preserved DNA methylation in every tissue. exposure: 28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L. cross_nutrient: B6 intersects methionine/folate metabolism; this experiment does not establish B12 or folate depletion. [b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
Complete structured claim and evidence
Cystathionine fractional synthesis increased by a mean 12% in eight of nine participants; plasma concentration rose 142 to 236 nmol/L.
Vitamin B6 → Cystathionine fractional synthesis rate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics.
exposure
28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L.
limitations
Fractional synthesis, pool size and total flux are distinct measurements.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A faster fractional rate for an intermediate can coexist with preserved overall pathway throughput.
primary_references
[b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1385–1395
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. · source_derived_draft · unverified_draft
### b6-fed-cystathionine-synthesis Cystathionine fractional synthesis increased by a mean 12% in eight of nine participants; plasma concentration rose 142 to 236 nmol/L. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A faster fractional rate for an intermediate can coexist with preserved overall pathway throughput. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–35), repeated postprandial isotope kinetics. limitations: Fractional synthesis, pool size and total flux are distinct measurements. exposure: 28 days dietary B6 restriction; plasma PLP49±4 to 19±2 nmol/L. [b6-lamers2011] Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women (2011). https://pubmed.ncbi.nlm.nih.gov/21430249/ DOI: 10.3945/jn.110.134197
Complete structured claim and evidence
Restriction did not significantly change glycine cleavage or serine synthesis from GCS-derived one-carbon units.
Vitamin B6 → Glycine cleavage flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6-dependent glycine cleavage supplies folate one-carbon chemistry.
experimental_model
Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion.
exposure
Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L.
limitations
Whole-body kinetics do not resolve separate organs or prove severe deficiency harmless.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This folate-linked carbon supply remained measurable despite lower blood B6.
primary_references
[b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1397–1408
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. · source_derived_draft · unverified_draft
### b6-glycine-cleavage-resilience Restriction did not significantly change glycine cleavage or serine synthesis from GCS-derived one-carbon units. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This folate-linked carbon supply remained measurable despite lower blood B6. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. limitations: Whole-body kinetics do not resolve separate organs or prove severe deficiency harmless. exposure: Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L. cross_nutrient: B6-dependent glycine cleavage supplies folate one-carbon chemistry. [b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184
Complete structured claim and evidence
SHMT-mediated glycine-to-serine conversion increased 182 to 205 micromol/kg/hour during restriction, accompanied by higher plasma glycine.
Vitamin B6 → Glycine-to-serine flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6 and folate participate in a reversible reaction; flux direction matters.
experimental_model
Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion.
exposure
Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L.
limitations
Do not substitute the reverse serine-to-glycine direction or identify the responsible SHMT compartment from whole-body data.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The measured direction ran faster, rather than shutting down.
primary_references
[b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1410–1421
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. · source_derived_draft · unverified_draft
### b6-glycine-serine-flux-increase SHMT-mediated glycine-to-serine conversion increased 182 to 205 micromol/kg/hour during restriction, accompanied by higher plasma glycine. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured direction ran faster, rather than shutting down. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. limitations: Do not substitute the reverse serine-to-glycine direction or identify the responsible SHMT compartment from whole-body data. exposure: Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L. cross_nutrient: B6 and folate participate in a reversible reaction; flux direction matters. [b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184
Complete structured claim and evidence
Plasma creatine decreased 40% in both meal states; creatinine fell 9% and dimethylglycine 16% postprandially.
Vitamin B6 → Creatine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Plasma metabolites connect B6 status with one-carbon metabolism without establishing a complete causal chain.
experimental_model
Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling.
exposure
28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications.
limitations
This does not establish exhausted SAM, impaired muscle phosphocreatine or a direct PLP requirement for creatine methylation.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6 restriction changed selected methylation-related metabolites.
primary_references
[b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1423–1434
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. · source_derived_draft · unverified_draft
### b6-restriction-creatine-profile Plasma creatine decreased 40% in both meal states; creatinine fell 9% and dimethylglycine 16% postprandially. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 restriction changed selected methylation-related metabolites. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. limitations: This does not establish exhausted SAM, impaired muscle phosphocreatine or a direct PLP requirement for creatine methylation. exposure: 28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications. cross_nutrient: Plasma metabolites connect B6 status with one-carbon metabolism without establishing a complete causal chain. [b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
Complete structured claim and evidence
3-Hydroxykynurenine increased 39% fasting and 34% after meals; kynurenic acid decreased 22% and 20%, respectively.
Vitamin B6 → 3-Hydroxy-L-kynurenine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6-dependent kynurenine reactions intersect the tryptophan-to-niacin network; conversion to NAD was not measured.
experimental_model
Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling.
exposure
28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications.
limitations
Does not measure brain neurotransmitters, tissue NAD synthesis or diagnose niacin deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Different branches of tryptophan processing left a detectable blood pattern.
primary_references
[b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1436–1447
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. · source_derived_draft · unverified_draft
### b6-restriction-kynurenine-profile 3-Hydroxykynurenine increased 39% fasting and 34% after meals; kynurenic acid decreased 22% and 20%, respectively. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different branches of tryptophan processing left a detectable blood pattern. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. limitations: Does not measure brain neurotransmitters, tissue NAD synthesis or diagnose niacin deficiency. exposure: 28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications. cross_nutrient: B6-dependent kynurenine reactions intersect the tryptophan-to-niacin network; conversion to NAD was not measured. [b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
Complete structured claim and evidence
Cystathionine increased 53% fasting and 76% postprandially; fasting serine increased 12%.
Vitamin B6 → Cystathionine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling.
exposure
28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications.
limitations
Shared restriction research program; not an independent demonstration of each molecular enzyme defect.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
More material accumulated at selected points in the network.
primary_references
[b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1449–1459
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. · source_derived_draft · unverified_draft
### b6-restriction-serine-cystathionine-profile Cystathionine increased 53% fasting and 76% postprandially; fasting serine increased 12%. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More material accumulated at selected points in the network. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. limitations: Shared restriction research program; not an independent demonstration of each molecular enzyme defect. exposure: 28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications. [b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
Complete structured claim and evidence
Supplementation improved plasma and erythrocyte PLP compared with placebo.
Pyridoxine → Plasma pyridoxal 5-prime-phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation.
exposure
Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation.
limitations
Selected low-PLP RA patients; blood response is not direct all-organ cofactor measurement.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The measured B6 pools responded to added pyridoxine.
primary_references
[b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1461–1471
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. · source_derived_draft · unverified_draft
### b6-ra-vitamer-response Supplementation improved plasma and erythrocyte PLP compared with placebo. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured B6 pools responded to added pyridoxine. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. limitations: Selected low-PLP RA patients; blood response is not direct all-organ cofactor measurement. exposure: Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation. [b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
Complete structured claim and evidence
Pyridoxine reduced the erythrocyte AST activation coefficient and improved post-tryptophan-load urinary xanthurenate response.
Pyridoxine → Erythrocyte aspartate aminotransferase activation coefficient source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation.
exposure
Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation.
limitations
Challenge tests and erythrocyte saturation do not identify every tissue defect.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Two B6-related functional tests improved, alongside blood vitamin levels.
primary_references
[b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1473–1483
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. · source_derived_draft · unverified_draft
### b6-ra-functional-tests Pyridoxine reduced the erythrocyte AST activation coefficient and improved post-tryptophan-load urinary xanthurenate response. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two B6-related functional tests improved, alongside blood vitamin levels. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. limitations: Challenge tests and erythrocyte saturation do not identify every tissue defect. exposure: Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation. [b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
Complete structured claim and evidence
The 2005 trial found no suppression of IL-6 or TNF production despite improved B6 markers.
Pyridoxine → IL6 source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation.
exposure
Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation.
limitations
Small short trial; a null finding is not proof that no population can respond. The CRP/ESR/RF table-versus-narrative reporting ambiguity is retained separately as an open question.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Correcting the vitamin measurements did not resolve the measured inflammation.
primary_references
[b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1485–1495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. · source_derived_draft · unverified_draft
### b6-ra-no-cytokine-suppression The 2005 trial found no suppression of IL-6 or TNF production despite improved B6 markers. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the vitamin measurements did not resolve the measured inflammation. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. limitations: Small short trial; a null finding is not proof that no population can respond. The CRP/ESR/RF table-versus-narrative reporting ambiguity is retained separately as an open question. exposure: Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation. [b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
Complete structured claim and evidence
The overall post-methionine homocysteine treatment effect was a nonsignificant trend (P=0.086); an elevated-baseline subgroup showed a stronger signal.
Pyridoxine → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Methionine handling depends on more than circulating B6.
experimental_model
Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation.
exposure
Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation.
limitations
Subgroup findings are exploratory; methotrexate, inflammation and enzyme differences can affect the challenge.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The homocysteine test did not improve as consistently as the other B6 tests.
primary_references
[b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1497–1508
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. · source_derived_draft · unverified_draft
### b6-ra-homocysteine-response-boundary The overall post-methionine homocysteine treatment effect was a nonsignificant trend (P=0.086); an elevated-baseline subgroup showed a stronger signal. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The homocysteine test did not improve as consistently as the other B6 tests. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Double-blind randomized placebo-controlled RA trial: 36 recruited, 33 baseline completers, 28 low-PLP patients eligible for supplementation. limitations: Subgroup findings are exploratory; methotrexate, inflammation and enzyme differences can affect the challenge. exposure: Pyridoxine hydrochloride 50 mg/day or placebo for 30 days; historical trial exposure, not a regimen recommendation. cross_nutrient: Methionine handling depends on more than circulating B6. [b6-chiang2005-trial] Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis (2005). https://pubmed.ncbi.nlm.nih.gov/16277693/ DOI: 10.1186/ar1839
Complete structured claim and evidence
In the 2010 cointervention trial, plasma IL-6 and TNF declined within the B6-plus-folic-acid group over 12 weeks.
Vitamin B6 → IL6 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folic acid was given to both arms; no biochemical B6–folate synergy established.
experimental_model
Single-blind randomized cointervention in 35 RA patients: 15 control and 20 B6.
exposure
Both groups folic acid 5 mg/day; B6 group also 100 mg/day for 12 weeks. Reported cytokine result is within-group change.
limitations
The accessed abstract reports within-group significance, not a demonstrated between-group change contrast. Plasma concentration differs from cytokine production; no automatic contradiction with 2005.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A different trial found a cytokine signal under a different exposure and measurement design.
primary_references
[b6-huang2010] Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis (2010). https://pubmed.ncbi.nlm.nih.gov/20571496/ DOI: 10.1038/ejcn.2010.107
tissue_or_cell_type
Human blood and whole-body measurements
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1510–1521
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind randomized cointervention in 35 RA patients: 15 control and 20 B6. · source_derived_draft · unverified_draft
### b6-ra-cointervention-cytokine-signal In the 2010 cointervention trial, plasma IL-6 and TNF declined within the B6-plus-folic-acid group over 12 weeks. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different trial found a cytokine signal under a different exposure and measurement design. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Single-blind randomized cointervention in 35 RA patients: 15 control and 20 B6. limitations: The accessed abstract reports within-group significance, not a demonstrated between-group change contrast. Plasma concentration differs from cytokine production; no automatic contradiction with 2005. exposure: Both groups folic acid 5 mg/day; B6 group also 100 mg/day for 12 weeks. Reported cytokine result is within-group change. cross_nutrient: Folic acid was given to both arms; no biochemical B6–folate synergy established. [b6-huang2010] Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis (2010). https://pubmed.ncbi.nlm.nih.gov/20571496/ DOI: 10.1038/ejcn.2010.107
Complete structured claim and evidence
RA patients had lower plasma PLP than controls but no significant difference in erythrocyte PLP, AST activation coefficient or urinary 4-pyridoxic acid.
Rheumatoid arthritis disease activity → Plasma pyridoxal 5-prime-phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Human cross-sectional comparison: 33 RA patients, 17 healthy controls; separate pair-fed rat adjuvant-arthritis experiment.
exposure
Human observational samples; rats studied at peak day 21 and chronic day 42 inflammation. Human arm shares recruitment program with supplementation study.
limitations
Cross-sectional association; disease, treatment and nutrition are not fully separable. Shared recruitment with related 2005 trial.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A low blood-plasma result did not mean that every measured B6 compartment was low.
primary_references
[b6-chiang2005-inflammation] Inflammation causes tissue-specific depletion of vitamin B6 (2005). https://pubmed.ncbi.nlm.nih.gov/16277678/ DOI: 10.1186/ar1821
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1523–1533
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cross-sectional comparison: 33 RA patients, 17 healthy controls; separate pair-fed rat adjuvant-arthritis experiment. · source_derived_draft · unverified_draft
### b6-ra-plasma-redcell-divergence RA patients had lower plasma PLP than controls but no significant difference in erythrocyte PLP, AST activation coefficient or urinary 4-pyridoxic acid. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low blood-plasma result did not mean that every measured B6 compartment was low. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Human cross-sectional comparison: 33 RA patients, 17 healthy controls; separate pair-fed rat adjuvant-arthritis experiment. limitations: Cross-sectional association; disease, treatment and nutrition are not fully separable. Shared recruitment with related 2005 trial. exposure: Human observational samples; rats studied at peak day 21 and chronic day 42 inflammation. Human arm shares recruitment program with supplementation study. [b6-chiang2005-inflammation] Inflammation causes tissue-specific depletion of vitamin B6 (2005). https://pubmed.ncbi.nlm.nih.gov/16277678/ DOI: 10.1186/ar1821
Complete structured claim and evidence
Pair-fed rats with adjuvant arthritis had lower plasma and liver PLP at peak/chronic inflammation, while muscle PLP and urinary 4-pyridoxic acid were not significantly changed.
Acute inflammation → Hepatic pyridoxal 5-prime-phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Human cross-sectional comparison: 33 RA patients, 17 healthy controls; separate pair-fed rat adjuvant-arthritis experiment.
exposure
Human observational samples; rats studied at peak day 21 and chronic day 42 inflammation. Human arm shares recruitment program with supplementation study.
limitations
Separate rat model; neither universal muscle preservation nor directly measured human liver deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
In this animal experiment, inflammation changed some B6 pools more than others despite matched food supply.
primary_references
[b6-chiang2005-inflammation] Inflammation causes tissue-specific depletion of vitamin B6 (2005). https://pubmed.ncbi.nlm.nih.gov/16277678/ DOI: 10.1186/ar1821
tissue_or_cell_type
Rat liver, skeletal muscle, plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1535–1545
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cross-sectional comparison: 33 RA patients, 17 healthy controls; separate pair-fed rat adjuvant-arthritis experiment. · source_derived_draft · unverified_draft
### b6-rat-inflammation-liver-muscle Pair-fed rats with adjuvant arthritis had lower plasma and liver PLP at peak/chronic inflammation, while muscle PLP and urinary 4-pyridoxic acid were not significantly changed. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this animal experiment, inflammation changed some B6 pools more than others despite matched food supply. organism: Rattus norvegicus tissue_or_cell_type: Rat liver, skeletal muscle, plasma and urine experimental_model: Human cross-sectional comparison: 33 RA patients, 17 healthy controls; separate pair-fed rat adjuvant-arthritis experiment. limitations: Separate rat model; neither universal muscle preservation nor directly measured human liver deficiency. exposure: Human observational samples; rats studied at peak day 21 and chronic day 42 inflammation. Human arm shares recruitment program with supplementation study. [b6-chiang2005-inflammation] Inflammation causes tissue-specific depletion of vitamin B6 (2005). https://pubmed.ncbi.nlm.nih.gov/16277678/ DOI: 10.1186/ar1821
Complete structured claim and evidence
During TNF-inhibitor therapy, disease-activity changes correlated with PLP and HK: XA changes; good responders showed a 31% PLP increase.
Rheumatoid arthritis disease activity → Plasma pyridoxal 5-prime-phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Longitudinal 106 RA patients beginning TNF-inhibitor therapy, assessed at baseline and three months.
exposure
Clinical TNF inhibitors; not randomized B6 supplementation.
limitations
Observational treatment-response association; cannot show B6 caused improvement. The 11% HK: XA decrease in good responders was not statistically significant (P=0.1).
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6 markers changed while inflammation was being treated, without a B6 intervention.
primary_references
[b6-sande2019] Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors (2019). https://pubmed.ncbi.nlm.nih.gov/31050750/ DOI: 10.1093/jn/nxz001
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1547–1557
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Longitudinal 106 RA patients beginning TNF-inhibitor therapy, assessed at baseline and three months. · source_derived_draft · unverified_draft
### b6-tnf-treatment-marker-change During TNF-inhibitor therapy, disease-activity changes correlated with PLP and HK: XA changes; good responders showed a 31% PLP increase. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 markers changed while inflammation was being treated, without a B6 intervention. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Longitudinal 106 RA patients beginning TNF-inhibitor therapy, assessed at baseline and three months. limitations: Observational treatment-response association; cannot show B6 caused improvement. The 11% HK: XA decrease in good responders was not statistically significant (P=0.1). exposure: Clinical TNF inhibitors; not randomized B6 supplementation. [b6-sande2019] Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors (2019). https://pubmed.ncbi.nlm.nih.gov/31050750/ DOI: 10.1093/jn/nxz001
Complete structured claim and evidence
All five volunteers developed sensory symptoms and quantitative sensory abnormalities; the 3 g/day group became symptomatic sooner than the 1 g/day group.
Pyridoxine → Sensory neuropathy source_derived_draftungraded
Experimental context and source evidence
availability_state
Experimental excess, not nutrient deficiency
experimental_model
Five healthy volunteers prospectively followed during experimental pyridoxine excess.
exposure
Pyridoxine 1 or 3 g/day, stopped with clinical/laboratory abnormality; very high historical exposures.
limitations
Five volunteers at gram doses; cannot determine a lowest toxic dose, safe upper intake or equivalence of different B6 forms.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
At very high exposure, more pyridoxine produced earlier sensory toxicity.
primary_references
[b6-berger1992] Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity (1992). https://pubmed.ncbi.nlm.nih.gov/1620347/ DOI: 10.1212/wnl.42.7.1367
tissue_or_cell_type
Peripheral sensory function
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1559–1570
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five healthy volunteers prospectively followed during experimental pyridoxine excess. · source_derived_draft · unverified_draft
### b6-pyridoxine-dose-latency All five volunteers developed sensory symptoms and quantitative sensory abnormalities; the 3 g/day group became symptomatic sooner than the 1 g/day group. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: At very high exposure, more pyridoxine produced earlier sensory toxicity. organism: Homo sapiens tissue_or_cell_type: Peripheral sensory function experimental_model: Five healthy volunteers prospectively followed during experimental pyridoxine excess. limitations: Five volunteers at gram doses; cannot determine a lowest toxic dose, safe upper intake or equivalence of different B6 forms. exposure: Pyridoxine 1 or 3 g/day, stopped with clinical/laboratory abnormality; very high historical exposures. availability_state: Experimental excess, not nutrient deficiency [b6-berger1992] Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity (1992). https://pubmed.ncbi.nlm.nih.gov/1620347/ DOI: 10.1212/wnl.42.7.1367
Complete structured claim and evidence
Thermal thresholds changed before or more strongly than vibration thresholds in the lower-dose group; sensory nerve-potential changes lagged thresholds in two of three subjects.
Pyridoxine → Quantitative sensory thresholds source_derived_draftungraded
Experimental context and source evidence
experimental_model
Five healthy volunteers prospectively followed during experimental pyridoxine excess.
exposure
Pyridoxine 1 or 3 g/day, stopped with clinical/laboratory abnormality; very high historical exposures.
limitations
Small experimental groups; not a diagnostic screening protocol.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Different nerve tests detected the developing injury at different times.
primary_references
[b6-berger1992] Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity (1992). https://pubmed.ncbi.nlm.nih.gov/1620347/ DOI: 10.1212/wnl.42.7.1367
tissue_or_cell_type
Peripheral sensory nerve function
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1572–1582
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five healthy volunteers prospectively followed during experimental pyridoxine excess. · source_derived_draft · unverified_draft
### b6-toxicity-early-sensory-tests Thermal thresholds changed before or more strongly than vibration thresholds in the lower-dose group; sensory nerve-potential changes lagged thresholds in two of three subjects. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different nerve tests detected the developing injury at different times. organism: Homo sapiens tissue_or_cell_type: Peripheral sensory nerve function experimental_model: Five healthy volunteers prospectively followed during experimental pyridoxine excess. limitations: Small experimental groups; not a diagnostic screening protocol. exposure: Pyridoxine 1 or 3 g/day, stopped with clinical/laboratory abnormality; very high historical exposures. [b6-berger1992] Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity (1992). https://pubmed.ncbi.nlm.nih.gov/1620347/ DOI: 10.1212/wnl.42.7.1367
Complete structured claim and evidence
Symptoms progressed for two to three weeks after pyridoxine withdrawal despite normalized serum PLP.
Pyridoxine → Sensory neuropathy source_derived_draftungraded
Experimental context and source evidence
experimental_model
Five healthy volunteers prospectively followed during experimental pyridoxine excess.
exposure
Pyridoxine 1 or 3 g/day, stopped with clinical/laboratory abnormality; very high historical exposures.
limitations
Demonstrates clinical timing; does not identify the molecular injury mechanism or prove irreversible damage.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A blood vitamin level returned to normal before the nerve symptoms stopped worsening.
primary_references
[b6-berger1992] Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity (1992). https://pubmed.ncbi.nlm.nih.gov/1620347/ DOI: 10.1212/wnl.42.7.1367
tissue_or_cell_type
Peripheral sensory function after exposure withdrawal
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1584–1594
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five healthy volunteers prospectively followed during experimental pyridoxine excess. · source_derived_draft · unverified_draft
### b6-toxicity-coasting Symptoms progressed for two to three weeks after pyridoxine withdrawal despite normalized serum PLP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blood vitamin level returned to normal before the nerve symptoms stopped worsening. organism: Homo sapiens tissue_or_cell_type: Peripheral sensory function after exposure withdrawal experimental_model: Five healthy volunteers prospectively followed during experimental pyridoxine excess. limitations: Demonstrates clinical timing; does not identify the molecular injury mechanism or prove irreversible damage. exposure: Pyridoxine 1 or 3 g/day, stopped with clinical/laboratory abnormality; very high historical exposures. [b6-berger1992] Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity (1992). https://pubmed.ncbi.nlm.nih.gov/1620347/ DOI: 10.1212/wnl.42.7.1367
Complete structured claim and evidence
After long-term 1250–1750 mg/day exposure, the reported patient recovered sensory function and nerve potentials following reduction to 500 mg/day.
Pyridoxine → Sensory neuropathy source_derived_draftungraded
Experimental context and source evidence
experimental_model
Single patient with homocystinuria and long-term high-dose pyridoxine exposure.
exposure
1250–1750 mg/day for 20 years; subsequently reduced to 500 mg/day. Case history, not evidence that the reduced dose is safe generally.
limitations
Single homocystinuria case; does not establish universal reversibility or safety of 500 mg/day. The article background statement about 50 mg is not treated as an experimentally determined threshold.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Recovery was possible in this individual despite long exposure.
primary_references
[b6-echanizlaguna2018] Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria (2018). https://pubmed.ncbi.nlm.nih.gov/29954767/ DOI: 10.1136/bcr-2018-225059
tissue_or_cell_type
Peripheral sensory nerves
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1596–1606
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single patient with homocystinuria and long-term high-dose pyridoxine exposure. · source_derived_draft · unverified_draft
### b6-toxicity-case-recovery After long-term 1250–1750 mg/day exposure, the reported patient recovered sensory function and nerve potentials following reduction to 500 mg/day. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Recovery was possible in this individual despite long exposure. organism: Homo sapiens tissue_or_cell_type: Peripheral sensory nerves experimental_model: Single patient with homocystinuria and long-term high-dose pyridoxine exposure. limitations: Single homocystinuria case; does not establish universal reversibility or safety of 500 mg/day. The article background statement about 50 mg is not treated as an experimentally determined threshold. exposure: 1250–1750 mg/day for 20 years; subsequently reduced to 500 mg/day. Case history, not evidence that the reduced dose is safe generally. [b6-echanizlaguna2018] Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria (2018). https://pubmed.ncbi.nlm.nih.gov/29954767/ DOI: 10.1136/bcr-2018-225059
Complete structured claim and evidence
All 14 hypophosphatasia patients had elevated plasma PLP; the mean was 1174 nM versus 57 nM in controls.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Plasma pyridoxal 5-prime-phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
ALPL links mineralization biology with B6 handling; this result alone does not imply calcium causes B6 deficiency.
experimental_model
Fourteen hypophosphatasia patients compared with 38 controls; urinary catabolite studied in four affected children.
exposure
Endogenous ALPL enzyme deficiency; ordinary dietary B6 in urinary subset.
limitations
Small heterogeneous disease cohort; concentrations are not diagnostic thresholds for general nutrition.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A high B6-related blood measurement can reflect faulty processing rather than extra intake.
primary_references
[b6-whyte1985] Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism (1985). https://pubmed.ncbi.nlm.nih.gov/4031070/ DOI: 10.1172/jci112031
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1608–1619
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fourteen hypophosphatasia patients compared with 38 controls; urinary catabolite studied in four affected children. · source_derived_draft · unverified_draft
### b6-hpp-high-plasma-plp All 14 hypophosphatasia patients had elevated plasma PLP; the mean was 1174 nM versus 57 nM in controls. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high B6-related blood measurement can reflect faulty processing rather than extra intake. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Fourteen hypophosphatasia patients compared with 38 controls; urinary catabolite studied in four affected children. limitations: Small heterogeneous disease cohort; concentrations are not diagnostic thresholds for general nutrition. exposure: Endogenous ALPL enzyme deficiency; ordinary dietary B6 in urinary subset. cross_nutrient: ALPL links mineralization biology with B6 handling; this result alone does not imply calcium causes B6 deficiency. [b6-whyte1985] Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism (1985). https://pubmed.ncbi.nlm.nih.gov/4031070/ DOI: 10.1172/jci112031
Complete structured claim and evidence
Urinary 4-pyridoxic acid was unremarkable in four affected children consuming normal dietary B6 despite markedly elevated plasma PLP.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → 4-Pyridoxic acid source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Fourteen hypophosphatasia patients compared with 38 controls; urinary catabolite studied in four affected children.
exposure
Endogenous ALPL enzyme deficiency; ordinary dietary B6 in urinary subset.
limitations
Small subset; normal urinary excretion does not prove normal every-tissue metabolism.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The circulating vitamin and its urinary breakdown product told different stories.
primary_references
[b6-whyte1985] Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism (1985). https://pubmed.ncbi.nlm.nih.gov/4031070/ DOI: 10.1172/jci112031
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1621–1631
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fourteen hypophosphatasia patients compared with 38 controls; urinary catabolite studied in four affected children. · source_derived_draft · unverified_draft
### b6-hpp-urinary-catabolite Urinary 4-pyridoxic acid was unremarkable in four affected children consuming normal dietary B6 despite markedly elevated plasma PLP. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The circulating vitamin and its urinary breakdown product told different stories. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Fourteen hypophosphatasia patients compared with 38 controls; urinary catabolite studied in four affected children. limitations: Small subset; normal urinary excretion does not prove normal every-tissue metabolism. exposure: Endogenous ALPL enzyme deficiency; ordinary dietary B6 in urinary subset. [b6-whyte1985] Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism (1985). https://pubmed.ncbi.nlm.nih.gov/4031070/ DOI: 10.1172/jci112031
Complete structured claim and evidence
In 150 affected children/adolescents, mean plasma pyridoxal was 66.7 versus 37.1 nM in controls; mean 4-pyridoxic acid did not differ.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Primary measurement study in 150 children/adolescents with hypophosphatasia and healthy pediatric comparators; adult observations separately discussed.
exposure
ALPL-related hypophosphatasia, variable clinical severity; plasma vitamers, not direct all-tissue cofactor measurement.
limitations
Cohort result cannot be transferred to every severe neonatal case; does not establish all-tissue sufficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
ALPL impairment did not make circulating pyridoxal universally low in this pediatric cohort.
primary_references
[b6-whyte2022] Hypophosphatasia: Vitamin B6 status of affected children and adults (2022). https://pubmed.ncbi.nlm.nih.gov/34547524/ DOI: 10.1016/j.bone.2021.116204
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1633–1643
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary measurement study in 150 children/adolescents with hypophosphatasia and healthy pediatric comparators; adult observations separately discussed. · source_derived_draft · unverified_draft
### b6-hpp-pediatric-pyridoxal In 150 affected children/adolescents, mean plasma pyridoxal was 66.7 versus 37.1 nM in controls; mean 4-pyridoxic acid did not differ. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: ALPL impairment did not make circulating pyridoxal universally low in this pediatric cohort. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Primary measurement study in 150 children/adolescents with hypophosphatasia and healthy pediatric comparators; adult observations separately discussed. limitations: Cohort result cannot be transferred to every severe neonatal case; does not establish all-tissue sufficiency. exposure: ALPL-related hypophosphatasia, variable clinical severity; plasma vitamers, not direct all-tissue cofactor measurement. [b6-whyte2022] Hypophosphatasia: Vitamin B6 status of affected children and adults (2022). https://pubmed.ncbi.nlm.nih.gov/34547524/ DOI: 10.1016/j.bone.2021.116204
Complete structured claim and evidence
In the 2025 cohort, untreated HPP had higher serum PLP and PLP: PL ratios; severe perinatal disease had lower PL than benign perinatal disease and the lowest PA across subtypes.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Serum PLP to pyridoxal ratio source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Over 100 hypophosphatasia cases, serum vitamers and available CSF; supplementation/enzyme-replacement subgroups.
exposure
Observational clinical sampling by subtype and treatment; no randomized B6 efficacy comparison.
limitations
Observational subtype comparison; contextual difference from broader pediatric cohorts, not an editorial conflict.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Disease severity changes which B6 forms accumulate or become low.
primary_references
[b6-akitomo2025] Vitamin B6 Status in Hypophosphatasia: Association With Clinical Severity, Diagnostic Utility, and Effects on Vitamin B6 Metabolism by Supplementation and Enzyme Replacement Therapy (2025). https://pubmed.ncbi.nlm.nih.gov/40387451/ DOI: 10.1002/jimd.70036
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1645–1655
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Over 100 hypophosphatasia cases, serum vitamers and available CSF; supplementation/enzyme-replacement subgroups. · source_derived_draft · unverified_draft
### b6-hpp-severity-vitamer-pattern In the 2025 cohort, untreated HPP had higher serum PLP and PLP: PL ratios; severe perinatal disease had lower PL than benign perinatal disease and the lowest PA across subtypes. Condition category: biomarker_context nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disease severity changes which B6 forms accumulate or become low. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Over 100 hypophosphatasia cases, serum vitamers and available CSF; supplementation/enzyme-replacement subgroups. limitations: Observational subtype comparison; contextual difference from broader pediatric cohorts, not an editorial conflict. exposure: Observational clinical sampling by subtype and treatment; no randomized B6 efficacy comparison. [b6-akitomo2025] Vitamin B6 Status in Hypophosphatasia: Association With Clinical Severity, Diagnostic Utility, and Effects on Vitamin B6 Metabolism by Supplementation and Enzyme Replacement Therapy (2025). https://pubmed.ncbi.nlm.nih.gov/40387451/ DOI: 10.1002/jimd.70036
Complete structured claim and evidence
Enzyme replacement was associated with lower serum PLP: PL ratios; CSF PL was higher in treated than untreated cases.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Serum PLP to pyridoxal ratio source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Over 100 hypophosphatasia cases, serum vitamers and available CSF; supplementation/enzyme-replacement subgroups.
exposure
Observational clinical sampling by subtype and treatment; no randomized B6 efficacy comparison.
limitations
Nonrandomized treatment comparisons; does not directly measure transport flux or establish neurological benefit.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Restoring enzyme activity changed B6 handling markers, including the sampled fluid around the brain.
primary_references
[b6-akitomo2025] Vitamin B6 Status in Hypophosphatasia: Association With Clinical Severity, Diagnostic Utility, and Effects on Vitamin B6 Metabolism by Supplementation and Enzyme Replacement Therapy (2025). https://pubmed.ncbi.nlm.nih.gov/40387451/ DOI: 10.1002/jimd.70036
tissue_or_cell_type
Serum and cerebrospinal fluid
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1657–1667
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Over 100 hypophosphatasia cases, serum vitamers and available CSF; supplementation/enzyme-replacement subgroups. · source_derived_draft · unverified_draft
### b6-hpp-enzyme-replacement-ratio Enzyme replacement was associated with lower serum PLP: PL ratios; CSF PL was higher in treated than untreated cases. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring enzyme activity changed B6 handling markers, including the sampled fluid around the brain. organism: Homo sapiens tissue_or_cell_type: Serum and cerebrospinal fluid experimental_model: Over 100 hypophosphatasia cases, serum vitamers and available CSF; supplementation/enzyme-replacement subgroups. limitations: Nonrandomized treatment comparisons; does not directly measure transport flux or establish neurological benefit. exposure: Observational clinical sampling by subtype and treatment; no randomized B6 efficacy comparison. [b6-akitomo2025] Vitamin B6 Status in Hypophosphatasia: Association With Clinical Severity, Diagnostic Utility, and Effects on Vitamin B6 Metabolism by Supplementation and Enzyme Replacement Therapy (2025). https://pubmed.ncbi.nlm.nih.gov/40387451/ DOI: 10.1002/jimd.70036
Complete structured claim and evidence
Depletion reduced circulating lymphocyte number/percentage and lymphocyte responses to T- and B-cell mitogens.
Vitamin B6 → Circulating lymphocyte count source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Eight healthy older adults in sequential dietary depletion and repletion experiment.
exposure
Depletion up to 20 days, then three 21-day repletion stages; final short 50 mg/day phase. Repletion-stage intakes are historical experimental context.
limitations
Eight-person sequential design; not evidence that supplementing adequate people prevents infection.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Too little B6 weakened measured immune-cell responses in this experiment.
primary_references
[b6-meydani1991] Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults (1991). https://pubmed.ncbi.nlm.nih.gov/2021134/ DOI: 10.1093/ajcn/53.5.1275
tissue_or_cell_type
Human circulating lymphocytes and ex-vivo cultures
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1669–1679
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight healthy older adults in sequential dietary depletion and repletion experiment. · source_derived_draft · unverified_draft
### b6-depletion-lymphocytes Depletion reduced circulating lymphocyte number/percentage and lymphocyte responses to T- and B-cell mitogens. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Too little B6 weakened measured immune-cell responses in this experiment. organism: Homo sapiens tissue_or_cell_type: Human circulating lymphocytes and ex-vivo cultures experimental_model: Eight healthy older adults in sequential dietary depletion and repletion experiment. limitations: Eight-person sequential design; not evidence that supplementing adequate people prevents infection. exposure: Depletion up to 20 days, then three 21-day repletion stages; final short 50 mg/day phase. Repletion-stage intakes are historical experimental context. [b6-meydani1991] Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults (1991). https://pubmed.ncbi.nlm.nih.gov/2021134/ DOI: 10.1093/ajcn/53.5.1275
Complete structured claim and evidence
IL-2 production declined during depletion; immune indices returned to baseline after the third repletion stage.
Vitamin B6 → IL-2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Eight healthy older adults in sequential dietary depletion and repletion experiment.
exposure
Depletion up to 20 days, then three 21-day repletion stages; final short 50 mg/day phase. Repletion-stage intakes are historical experimental context.
limitations
Recovery occurred during a sequence of increasing intakes; no universal individual requirement or treatment dose follows.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The observed immune changes were reversible with restored intake.
primary_references
[b6-meydani1991] Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults (1991). https://pubmed.ncbi.nlm.nih.gov/2021134/ DOI: 10.1093/ajcn/53.5.1275
tissue_or_cell_type
Ex-vivo human immune-cell assays
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1681–1691
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight healthy older adults in sequential dietary depletion and repletion experiment. · source_derived_draft · unverified_draft
### b6-depletion-il2 IL-2 production declined during depletion; immune indices returned to baseline after the third repletion stage. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The observed immune changes were reversible with restored intake. organism: Homo sapiens tissue_or_cell_type: Ex-vivo human immune-cell assays experimental_model: Eight healthy older adults in sequential dietary depletion and repletion experiment. limitations: Recovery occurred during a sequence of increasing intakes; no universal individual requirement or treatment dose follows. exposure: Depletion up to 20 days, then three 21-day repletion stages; final short 50 mg/day phase. Repletion-stage intakes are historical experimental context. [b6-meydani1991] Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults (1991). https://pubmed.ncbi.nlm.nih.gov/2021134/ DOI: 10.1093/ajcn/53.5.1275
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.

PDXK A228T nucleotide handling

Condition: machinery_impairment · A228T substitution.

Normal role: PDXK uses ATP to phosphorylate vitamers.

Recorded consequence: Impaired nucleotide-dependent activity.

Scope: Recombinant human enzyme.

Biallelic PDXK A228T

Condition: machinery_impairment · Homozygous A228T.

Normal role: PDXK forms phosphorylated vitamers.

Recorded consequence: Reduced kinase activity.

Scope: Patient erythrocytes.

Biallelic PDXK R220Q

Condition: machinery_impairment · Homozygous R220Q.

Normal role: PDXK forms phosphorylated vitamers.

Recorded consequence: Reduced kinase activity.

Scope: Patient erythrocytes.

Pdxp deletion raises tissue PLP

Condition: machinery_impairment · Ubiquitous Pdxp deletion.

Normal role: Pdxp degrades PLP.

Recorded consequence: Higher tissue PLP.

Scope: Mouse tissues.

ALPL deficiency reduces extracellular processing

Condition: machinery_impairment · Inherited hypophosphatasia.

Normal role: ALPL hydrolyzes extracellular PLP.

Recorded consequence: Reduced PLP phosphatase activity.

Scope: Patient fibroblasts.

PNPO IVS3-1G>A splice-site impairment

Condition: machinery_impairment · Human IVS3-1G>A splice-site variant.

Normal role: PNPO oxidizes phosphorylated precursors.

Recorded consequence: Null measured PNPO activity.

Scope: Human construct in CHO cells.

PNPO X262Q stop-loss impairment

Condition: machinery_impairment · Human X262Q stop-loss variant.

Normal role: PNPO oxidizes phosphorylated precursors.

Recorded consequence: Null measured PNPO activity.

Scope: Human construct in CHO cells.

When acetaldehyde strips the active form of vitamin B6

Condition: nutrient_deficiency · Acetaldehyde produced from ethanol, which displaces PLP so the phosphatase can act.

Normal role: Pyridoxal is phosphorylated to pyridoxal 5-phosphate, the coenzyme form, and a membrane phosphatase removes the phosphate again.

Recorded consequence: Plasma PLP falls, and more than half of alcoholic subjects without liver disease are below the lowest control value.

Scope: Human plasma survey and erythrocyte experiments

PLPBP R241Q binding defect

Condition: machinery_impairment · R241Q substitution.

Normal role: PLPBP binds PLP.

Recorded consequence: Lower cofactor occupancy after purification.

Scope: Recombinant protein.

PLPBP-deficient fibroblasts in 2016 study

Condition: machinery_impairment · Patient biallelic PLPBP impairment.

Normal role: PLPBP contributes to PLP homeostasis.

Recorded consequence: PLP accumulated in this culture model.

Scope: Human fibroblasts.

PLPBP deficiency in defined vitamer cultures

Condition: machinery_impairment · Patient deletion or engineered PLPBP loss.

Normal role: PLPBP supports regulated PLP pools.

Recorded consequence: Lower PLP in the studied cultures.

Scope: Fibroblast and HEK293 models.

PDXP silencing in PLPBP-null cells

Condition: machinery_impairment · PDXP siRNA in PLPBP-null HEK293.

Normal role: PDXP hydrolyzes PLP.

Recorded consequence: Higher retained PLP.

Scope: Cultured human cells.

SLC25A38 loss separates mitochondrial from cellular PLP

Condition: machinery_impairment · Engineered knockout.

Normal role: SLC25A38 supports mitochondrial PLP accumulation.

Recorded consequence: Lower mitochondrial PLP.

Scope: K562 cells.

SLC25A38 R134C fails cellular rescue

Condition: machinery_impairment · R134C expressed in knockout.

Normal role: Wild-type supports accumulation.

Recorded consequence: Failed rescue.

Scope: K562 cells.

CTH Thr67Ile-associated catalytic impairment

Condition: machinery_impairment · Thr67Ile substitution

Normal role: Cleaves cystathionine

Recorded consequence: Lower expressed-enzyme activity

Scope: Variant protein and reported patients

ALAS2 Arg452Cys cofactor-use defect

Condition: machinery_impairment · Arg452Cys substitution

Normal role: PLP-dependent ALA formation

Recorded consequence: Altered cofactor and substrate kinetics

Scope: Recombinant human enzyme

ALAS2 Met567Val partner-binding defect

Condition: machinery_impairment · Met567Val substitution

Normal role: ALAS2 binds SUCLA2

Recorded consequence: Reduced partner binding

Scope: Recombinant human proteins; XLSA-associated variant

Dietary B6 withdrawal in the rat tryptophan-niacin pathway

Condition: nutrient_deficiency · 19 days of B6-free diet, with niacin-free comparator groups

Normal role: PLP supports kynurenine-pathway enzymes

Recorded consequence: Altered urinary pathway readouts

Scope: Controlled rat diets

Engineered SCLY substrate-specificity change

Condition: machinery_impairment · Engineered Asp146Lys substitution

Normal role: Preferential cleavage of selenocysteine

Recorded consequence: Acquired sulfur-substrate activity

Scope: In-vitro variant

Vigabatrin inhibition of GABA aminotransferase

Condition: machinery_impairment · Enzyme exposed to vigabatrin.

Normal role: PLP supports GABA degradation.

Recorded consequence: Covalent enzyme-cofactor-drug adduct.

Scope: Pig liver enzyme.

ALDH7A1 impairment and PLP sequestration

Condition: machinery_impairment · Biallelic ALDH7A1 disease variants.

Normal role: Antiquitin removes alpha-aminoadipic semialdehyde.

Recorded consequence: Accumulating P6C can consume PLP.

Scope: Patient and biochemical evidence.

Ginkgotoxin competition at PDXK

Condition: machinery_impairment · Ginkgotoxin in purified-enzyme incubations.

Normal role: PDXK phosphorylates vitamin B6 substrates.

Recorded consequence: Reduced pyridoxal phosphorylation.

Scope: Human enzyme in vitro.

Theophylline inhibition of PDXK

Condition: machinery_impairment · Theophylline added to purified human enzyme.

Normal role: PDXK generates phosphorylated B6.

Recorded consequence: Inhibition of kinase activity.

Scope: In-vitro kinetics and crystals.

PIH exposure and ferrochelatase abundance

Condition: machinery_impairment · Experimental PIH exposure.

Normal role: FECH completes heme synthesis.

Recorded consequence: Lower FECH protein.

Scope: Human liver-cell models.

B6 restriction changes blood pools without erasing cysteine turnover

Condition: nutrient_deficiency · Four-week dietary restriction in healthy young adults.

Normal role: PLP supports transsulfuration enzymes.

Recorded consequence: Cystathionine and total plasma glutathione rose; measured cysteine turnover did not decline.

Scope: Nine volunteers, overnight-fasted tracer protocol.

Post-meal methylation and sulfur-pathway rates can be resilient

Condition: nutrient_deficiency · 28-day dietary B6 restriction.

Normal role: PLP-dependent enzymes participate in sulfur and one-carbon metabolism.

Recorded consequence: Mean major fluxes were preserved despite lower PLP and altered cystathionine synthesis.

Scope: Nine healthy young adults, fed-state tracers.

Glycine-related one-carbon reactions respond unequally

Condition: nutrient_deficiency · Moderate dietary restriction in healthy adults.

Normal role: PLP-dependent GCS and SHMT reactions connect glycine with folate carbon units.

Recorded consequence: Glycine accumulated while measured glycine cleavage was maintained and glycine-to-serine conversion increased.

Scope: Thirteen adults, isotope kinetics.

B6 restriction leaves a selective metabolite pattern

Condition: nutrient_deficiency · 28 days of controlled low B6 intake.

Normal role: PLP-dependent enzymes contribute to amino-acid and tryptophan metabolism.

Recorded consequence: Several one-carbon and kynurenine-pathway concentrations shifted.

Scope: Twenty-three healthy adults; plasma LC-MS/MS.

Improving B6 tests does not guarantee less inflammation

Condition: biomarker_context · Low-PLP rheumatoid arthritis with supplementation.

Normal role: PLP supports aminotransferase and tryptophan-pathway functions.

Recorded consequence: Several B6 markers improved without demonstrated suppression of inflammatory cytokine production in the 2005 trial.

Scope: Randomized 28-patient study; historical 50 mg/day exposure.

Inflammation changes the meaning of a B6 blood result

Condition: biomarker_context · Inflammatory disease or experimentally induced inflammation.

Normal role: B6 resides in multiple compartments.

Recorded consequence: Plasma PLP may fall while erythrocyte or muscle pools remain stable.

Scope: Human RA observations and separately labeled rat experiment.

Rat inflammation changes liver and muscle B6 pools differently

Condition: biomarker_context · Adjuvant arthritis with pair-fed controls.

Normal role: B6 resides in multiple compartments.

Recorded consequence: Plasma PLP may fall while erythrocyte or muscle pools remain stable.

Scope: Rat liver, skeletal muscle, plasma and urine at days 21 and 42.

B6 markers change during anti-inflammatory treatment

Condition: biomarker_context · Three-month clinical TNF-inhibitor treatment in RA.

Normal role: B6 resides in multiple compartments.

Recorded consequence: Plasma PLP may fall while erythrocyte or muscle pools remain stable.

Scope: 106 RA patients; observational treatment-response analysis.

ALPL impairment can raise circulating PLP without uniform tissue excess

Condition: machinery_impairment · Hypophosphatasia from ALPL dysfunction.

Normal role: Cell-surface ALPL helps process extracellular phosphorylated B6.

Recorded consequence: Circulating vitamer concentrations and ratios depend on enzyme activity and disease severity.

Scope: Human hypophosphatasia studies across ages and subtypes.

ALPL impairment can raise circulating PLP without uniform tissue excess

Condition: biomarker_context · Hypophosphatasia from ALPL dysfunction.

Normal role: Cell-surface ALPL helps process extracellular phosphorylated B6.

Recorded consequence: Circulating vitamer concentrations and ratios depend on enzyme activity and disease severity.

Scope: Human hypophosphatasia studies across ages and subtypes.

Dietary depletion can impair measured immune-cell responses

Condition: nutrient_deficiency · Short controlled depletion in eight older adults.

Normal role: PLP supports metabolism needed by immune cells.

Recorded consequence: Lymphocyte indices and IL-2 production fell and returned toward baseline during repletion.

Scope: Sequential human dietary experiment with ex-vivo immune assays.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

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Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which organ-specific B6-dependent fluxes fail first as deficiency becomes severe or prolonged?Short marginal restriction in healthy adults preserved several group-mean whole-body rates; it does not rank every organ or enzyme.
Why did total plasma glutathione rise during fasting B6 restriction?The measured pool increase did not establish intracellular reduced GSH, synthesis rate or a unique compensation mechanism.
Which cellular mechanism and exposure history determine individual susceptibility to pyridoxine neuropathy?High-dose prospective observations establish toxicity and delayed recovery timing, but not the lowest harmful intake or one proved molecular mechanism.
Does correcting B6 status improve inflammatory disease outcomes in a defined subgroup?Biochemical correction, within-group cytokine changes and disease-response correlations are different evidence; larger comparable trials would be needed.
Can combined blood vitamer measurements predict B6 availability in each tissue across hypophosphatasia subtypes?Serum and CSF patterns improve interpretation but do not directly quantify intracellular enzyme-bound PLP everywhere.
How should the CRP, ESR and rheumatoid-factor treatment P values in Chiang 2005 Table 3 be reconciled with its discussion?Table 3 displays P<0.0001 for those treatment comparisons, while the narrative reports no anti-inflammatory improvement. Statistical change need not mean improvement; aggregate data cannot resolve the analysis or possible reporting error. The unambiguous cytokine-production null result is retained separately.
A shared PLP requirement does not show that mild dietary B6 restriction uniformly depresses all of these pathways.Enzyme saturation, substrates, compartmentation and protein abundance can compensate; purified enzymes do not establish universal blood thresholds.
Dietary B6 deficiency causing failure of selenium repletion through SCLY is not established by the curated SCLY structure study.The paper tested protein structure and substrate discrimination, not dietary depletion or selenium supplementation. Existing cell studies also show cell-dependent SCLY requirements.
Direct transfer of selenium from human SCLY to SEPHS2 remains a proposed connection in this evidence set.A mobile active-site region permits a delivery model, but this paper did not directly measure SCLY-to-SEPHS2 transfer.
Chicken GLDC kinetic findings cannot be reported as measured human GLDC kinetics.The human paper here is a cloning/sequence study; the purified enzyme study used chicken liver.
ALAS1 B6-depletion sensitivity has not been quantified by the ALAS1 regulation paper included here.The primary human experiment manipulated bile-acid/FXR signaling. ALAS2 cofactor results must not be reassigned to ALAS1.
Does pyridoxine inhibit neuronal PDXK sufficiently to cause human sensory neuropathy?The curated pyridoxine study tested cell viability and other enzymes, not neuronal PDXK inhibition as a causal mediator. Ginkgotoxin inhibition cannot substitute for pyridoxine evidence.
What net brain GABA response follows a particular B6 exposure?B6-dependent synthesis and degradation coexist; enzyme structures do not quantify compartmental flux or clinical responses.
What function does the pig GABA-AT iron-sulfur cluster serve?The structural study identified the cluster but did not establish its function or an iron-B6 nutritional dependency.
Are non-pyridoxine vitamers safe across human doses and exposure durations?The negative comparator cell assays cannot establish that broader claim.
Which neuronal consequences of ALDH7A1 loss are caused specifically by local PLP sequestration?The metabolite-cofactor chemistry is direct, but it does not fully map every downstream neuronal mechanism.
Does PIH directly damage the FECH iron-sulfur cluster?Cellular protein loss and chelation do not identify the exact iron-handling step.
The uptake carrier underlying Caco-2 PN kinetics was not molecularly identified in Said 2003.Do not assign an SLC gene from kinetic behavior alone.
The quantitative human contribution of intact PLP absorption remains unresolved by these rat and cell experiments.Rat hydrolysis-protected preparations support apparent intact transport; hydrolysis studies test a different step.
Direct transport of PLP by SLC25A38 has not been established.The 2025 cellular data permit import, retention or indirect regulation; proteoliposome experiments were requested by the authors.
PLPBP direct delivery of PLP to apoenzymes remains unresolved.Physical PLP binding and cellular rescue do not themselves demonstrate transfer to a recipient enzyme.
PLPBP-deficient cultures show opposite bulk-PLP directions across studies.Different genotypes and medium conditions prevent a same-condition contradiction; 2023 authors explicitly discuss culture composition as a possible explanation.
The human quantitative catabolic contribution of NAD-dependent oxidation versus aldehyde oxidase is not established here.The primary alternative-pathway experiment was in rats and did not identify a human ALDH isoenzyme.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Vitamin B6

The mechanisms

Rat jejunal perfusion and in-vitro assays demonstrated phosphatase-mediated hydrolysis of luminal PLP.

Albumin binding inhibited hydrolysis of 2 micromolar PLP at pH 5-7.4; at pH 3-4 binding was negligible and hydrolysis persisted.

Hydrolysis-protected rat intestinal sacs showed serosal PLP appearance; the authors interpreted accompanying venous data as supporting some direct phosphorylated-PLP absorption.

Caco-2 pyridoxine uptake was energy-dependent and sodium-independent; saturation occurred at pH 5.5 (apparent Km 11.99 micromolar), but not pH 7.4.

Polarized Caco-2 cells supplied apically with PN generated PL and released more PL basolaterally than apically.

Polarized Caco-2 cells supplied apically with PM generated PL and released more PL basolaterally than apically.

During apical PL incubation, basolateral PL appearance approximately matched apical disappearance, without detectable medium PLP or PMP.

Purified recombinant human PDXK phosphorylated pyridoxine to its corresponding 5-prime phosphate.

Purified recombinant human PDXK phosphorylated pyridoxamine to its corresponding 5-prime phosphate.

Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions.

Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity.

ATPgammaS binding was detected for wild-type PDXK but not A228T under the ITC conditions; A228T also required higher MgATP for half-maximal activity.

Homozygous A228T cases had PDXK activities of 0.8 and 1.1 pmol per dried-blood-spot punch per hour; controls ranged 2.6-14.7.

Homozygous R220Q cases had PDXK activities of 0.5 and 1.19 pmol per dried-blood-spot punch per hour; controls ranged 2.6-14.7.

Catalytically active recombinant human pyridoxal phosphatase hydrolyzed pyridoxal-phosphate.

Catalytically active recombinant human pyridoxal phosphatase hydrolyzed pyridoxine-phosphate.

Human erythrocyte pyridoxal phosphatase required divalent cations; magnesium activated PLP hydrolysis with Michaelis-Menten behavior.

Ubiquitous Pdxp deletion raised PLP in brain, skeletal muscle and red cells by up to threefold compared with controls.

Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation.

Hypophosphatasia fibroblasts retained only 2-5% of control phosphatase activity toward PLP and other tested substrates.

Equilibrium dialysis found one higher-affinity human-albumin PLP-binding site (Kd 8.7 micromolar) and additional lower-affinity sites.

Pyridoxal and 4-pyridoxic acid inhibited PLP binding to human serum albumin in vitro.

The human PNPO IVS3-1G>A splice-site construct had no detectable PNPO activity in the reported CHO expression assay.

The human PNPO X262Q stop-loss construct had no detectable PNPO activity in the reported CHO expression assay.

Mass spectrometry of reduced recombinant human PLPBP identified Lys47 as the PLP-binding residue; spectroscopy supported an internal aldimine.

Purified R241Q lacked detectable bound PLP, but a fourfold molar PLP excess produced a mixture including holo-protein.

PLPBP-deficient patient fibroblasts in Darin 2016 accumulated approximately two- to threefold more PLP than controls in the tested culture medium.

In the 2023 study, PLP was lower in PLPBP-deficient fibroblasts and HEK293 cells after 96 hours with 20 micromolar PN, PM or PL.

Forty-eight-hour PDXP siRNA restored PLP toward control concentrations in PLPBP-deficient HEK293 cells and decreased PL.

At 10 nM extracellular PN, SLC25A38-null K562 mitochondria had about 3.9-fold lower PLP despite no whole-cell depletion.

After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria.

R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back.

Partially purified rat tissue NAD-dependent aldehyde-dehydrogenase activity oxidized PL to 4-pyridoxic acid; oxidase-null rats still excreted the acid.

The human CBS catalytic core binds PLP through its active-site lysine; this site is separate from the heme-binding region.

PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine.

The human CBS structure resolves a heme-binding region distinct from the PLP catalytic site.

PLP binds human CTH at Lys212 in an active site assembled from adjacent subunits.

Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction.

Expressed human CTH Thr67Ile had 13% of wild-type catalytic activity in the 2009 study.

Vitamin B6 administration lowered plasma cystathionine in the reported CTH Thr67Ile homozygote.

Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool.

Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.

Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.

Adding PLP shifted purified human SHMT2 from dimers toward tetramers.

Human SHMT1 remained tetrameric with and without PLP in the tested solution conditions.

Purified chicken glycine decarboxylase contained approximately one PLP molecule per subunit.

Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold.

Human GLDC cDNA sequencing identified a conserved PLP-binding lysine region corresponding to the chicken enzyme.

Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein.

Human BCAT2 crystal structures show PLP covalently linked to the active-site lysine in active enzyme forms.

Human BCAT2 structures capture the isoleucine ketimine and PMP forms of its amino-transfer cycle.

Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.

Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.

Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate.

Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate.

Cryo-EM of human liver mitochondria resolved PLP in GOT2, with residues from both subunits forming its binding pocket.

Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT.

The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391.

Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide.

ALAS2 Arg452Cys showed reduced PLP affinity and altered succinyl-CoA kinetics despite retained SUCLA2 binding.

ALAS2 Met567Val retained normal activity in purified assays but showed markedly reduced retention on SUCLA2 affinity columns.

Chenodeoxycholic acid increased ALAS1 mRNA and enzyme activity in primary human hepatocytes and liver slices through an FXR-linked regulatory mechanism.

Rabbit muscle phosphorylase crystallography located PLP buried next to the catalytic glucose-binding site.

A labeled cofactor-analogue experiment supported direct participation of the PLP phosphate group in glycogen phosphorylase glucosyl transfer.

Human kynureninase crystallography resolves the PLP-containing active-site architecture.

Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP.

Under niacin-free feeding, B6-free rats had lower apparent tryptophan-to-niacin conversion than rats receiving B6.

Both B6-free rat diet groups showed substantially increased urinary xanthurenate relative to B6-containing groups.

Human SCLY has two cofactor-containing active sites at its homodimer interface, with both subunits contributing to each site.

Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays.

PLP-bound human GAD67 catalyzes glutamate decarboxylation to GABA.

PLP-bound human GAD65 catalyzes glutamate decarboxylation to GABA.

GAD65 catalytic-loop mobility favors a side reaction producing succinic semialdehyde and releasing the converted cofactor as PMP.

GAD65/GAD67 chimera experiments implicated the C-terminal domain, together with the catalytic loop, in controlling auto-inactivation.

Expressed human DDC decarboxylated L-DOPA; added PLP enhanced the measured activity.

Expressed human DDC decarboxylated 5-hydroxy-L-tryptophan; added PLP enhanced the measured activity.

Human apoDDC has exposed active sites; PLP-titrated structures and kinetics support a cofactor-linked conformational transition.

Human holoDDC crystallography resolved an internal PLP aldimine at 1.9 angstrom resolution.