PLP

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence_access

Primary full text, enzyme characterization

experimental_model

Human recombinant CSAD biochemical characterization.

limitations

Cofactor dependence does not establish that extra B6 increases taurine in a replete person.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

CSAD needs the active B6 cofactor, not just its cysteine-derived substrate.

primary_references

A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 41–47

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant CSAD biochemical characterization. · source_derived_draft · unverified_draft

## taurine-csad-plp CSAD needs the active B6 cofactor, not just its cysteine-derived substrate. The purified human CSAD characterized in this study was a PLP-dependent enzyme, linking its decarboxylation chemistry to the active cofactor form of vitamin B6. Model: Human recombinant CSAD biochemical characterization. Limitations: Cofactor dependence does not establish that extra B6 increases taurine in a replete person. Evidence access: Primary full text, enzyme characterization A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438

cross_nutrient

B6-product feedback regulates a B2-dependent enzyme.

evidence_location

Results: kinetic properties; Table 1; FMN-binding structure

experimental_model

Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.

exposure

Purified-enzyme assay

limitations

The paper did not establish free PLP pools or inhibition magnitude in intact mammalian tissues.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The active B6 product can slow its own formation in vitro.

primary_references

[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203

tissue_or_cell_type

Purified recombinant enzyme; no intact tissue

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1178–1190

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft

### b2-pnp-product-inhibition PLP competitively inhibited purified human PNPO in the reported kinetic assays. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active B6 product can slow its own formation in vitro. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: The paper did not establish free PLP pools or inhibition magnitude in intact mammalian tissues. exposure: Purified-enzyme assay cross_nutrient: B6-product feedback regulates a B2-dependent enzyme. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203

evidence_access

Primary abstract

experimental_model

Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons.

limitations

No demonstrated B6-dependent synthesis in human cells.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The active vitamin B6 cofactor participates in microbial synthesis.

primary_references

Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 200–206

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons. · source_derived_draft · unverified_draft

## ergothioneine-egte-plp The active vitamin B6 cofactor participates in microbial synthesis. Purified Mycobacterium smegmatis EgtE catalyzed a PLP-dependent C-S lyase reaction in ergothioneine biosynthesis. Model: Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons. Limitations: No demonstrated B6-dependent synthesis in human cells. Evidence access: Primary abstract Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

evidence_access

Primary abstract

experimental_model

Recombinant human enzyme spectroscopy and kinetics.

limitations

Enzyme dependence does not establish dietary B6 limitation or that adding B6 treats TAT genetic deficiency.

nutrient_topic

L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine

plain_language

The active B6 form participates in tyrosine breakdown.

primary_references

The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme spectroscopy and kinetics. · source_derived_draft · unverified_draft

## l-tyrosine-tat-b6 The active B6 form participates in tyrosine breakdown. Human TAT is PLP dependent, with spectroscopic analysis of its cofactor-linked aldimine. Model: Recombinant human enzyme spectroscopy and kinetics. Limitations: Enzyme dependence does not establish dietary B6 limitation or that adding B6 treats TAT genetic deficiency. Evidence access: Primary abstract The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x

evidence_access

Primary full text

experimental_model

Purified human PSAT spectroscopy, substrate addition and crystallography.

limitations

PLP is recycled in catalysis; the experiment does not show one dietary B6 molecule is consumed for each serine made.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

The B6 cofactor cycles between forms as it carries amino-group chemistry.

primary_references

L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 38–44

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human PSAT spectroscopy, substrate addition and crystallography. · source_derived_draft · unverified_draft

## l-serine-psat-plp The B6 cofactor cycles between forms as it carries amino-group chemistry. Human PSAT contained a PLP internal aldimine associated with Lys200; glutamate converted the cofactor toward its pyridoxamine-phosphate state during the first half-reaction. Model: Purified human PSAT spectroscopy, substrate addition and crystallography. Limitations: PLP is recycled in catalysis; the experiment does not show one dietary B6 molecule is consumed for each serine made. Evidence access: Primary full text L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609

evidence_access

Primary abstract

experimental_model

Purified wild-type and engineered human enzymes.

limitations

This manipulation does not show that additional B6 restores a mutant enzyme or that ordinary dietary B6 is limiting.

nutrient_topic

L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine

plain_language

B6-dependent chemistry also depends on the enzyme structure that binds its cofactor.

primary_references

Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 266–272

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified wild-type and engineered human enzymes. · source_derived_draft · unverified_draft

## l-threonine-human-sds-plp B6-dependent chemistry also depends on the enzyme structure that binds its cofactor. Deleting Pro128 from human hepatic SDS changed substrate kinetic constants and affinity for pyridoxal phosphate. Model: Purified wild-type and engineered human enzymes. Limitations: This manipulation does not show that additional B6 restores a mutant enzyme or that ordinary dietary B6 is limiting. Evidence access: Primary abstract Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

evidence_access

Primary abstract

experimental_model

Purified human SRR crystal structure.

limitations

Structural cofactor binding does not establish dietary B6 control of human D-aspartate or an effective supplementation threshold.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Vitamin B6-derived PLP is part of the shared racemase machinery.

primary_references

Conformational flexibility within the small domain of human serine racemase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32039887/ · DOI 10.1107/S2053230X20001193

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 56–62

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human SRR crystal structure. · source_derived_draft · unverified_draft

## d-aspartate-srr-plp Vitamin B6-derived PLP is part of the shared racemase machinery. The 1.89-angstrom human serine-racemase holoenzyme structure included its bound pyridoxal-phosphate cofactor. Model: Purified human SRR crystal structure. Limitations: Structural cofactor binding does not establish dietary B6 control of human D-aspartate or an effective supplementation threshold. Evidence access: Primary abstract Conformational flexibility within the small domain of human serine racemase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32039887/ · DOI 10.1107/S2053230X20001193

evidence_access

Primary abstract

experimental_model

Mouse high-fat-diet and brown-adipocyte experiments.

limitations

Abstract-only intervention details; no human dose, route equivalence or cysteine-plus-B6 synergy is established.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A B6-derived coenzyme and a sulfur donor were separately tested inputs to this pathway.

primary_references

Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 412–418

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse high-fat-diet and brown-adipocyte experiments. · source_derived_draft · unverified_draft

## l-cysteine-cars2-plp-intervention A B6-derived coenzyme and a sulfur donor were separately tested inputs to this pathway. PLP treatment or an H2S donor improved brown-adipocyte function and reduced obesity progression in the reported high-fat-fed mouse experiments. Model: Mouse high-fat-diet and brown-adipocyte experiments. Limitations: Abstract-only intervention details; no human dose, route equivalence or cysteine-plus-B6 synergy is established. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

evidence_span

{"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"}

experimental_model

Recombinant enzyme crystal structure

exposure

PLP-bound enzyme structure

limitations

The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human OAT

plain_language

Vitamin B6 has a defined role in the machinery handling ornithine.

primary_references

[citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

tissue_or_cell_type

Mitochondrial ornithine transamination

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 333–344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme crystal structure · source_derived_draft · unverified_draft

### citrulline-oat-plp Human OAT bound pyridoxal phosphate through a Schiff base to Lys292. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B6 has a defined role in the machinery handling ornithine. organism: Human OAT tissue_or_cell_type: Mitochondrial ornithine transamination experimental_model: Recombinant enzyme crystal structure limitations: The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine. exposure: PLP-bound enzyme structure evidence_span: {"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"} [citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

evidence_span

{"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"}

experimental_model

Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay

exposure

PLP quantification, cysteine desulfurase assays and Moco/MPT binding

limitations

Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Human genetics and human MOCOS proteins; plant XDH variant experiment separately

plain_language

Vitamin B6 chemistry helps supply the sulfur used to activate these molybdenum enzymes.

primary_references

[mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788

tissue_or_cell_type

Patient samples and purified domains

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 534–545

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay · source_derived_draft · unverified_draft

### mo-mocos-plp The purified human MOCOS NifS-like domain bound PLP and exhibited cysteine desulfurase activity. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B6 chemistry helps supply the sulfur used to activate these molybdenum enzymes. organism: Human genetics and human MOCOS proteins; plant XDH variant experiment separately tissue_or_cell_type: Patient samples and purified domains experimental_model: Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay limitations: Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains. exposure: PLP quantification, cysteine desulfurase assays and Moco/MPT binding evidence_span: {"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"} [mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788

evidence_access

Primary abstract

experimental_model

Human and Leishmania ODC comparison; human inhibitor-bound structure.

limitations

Cofactor dependence does not establish that extra B6 raises polyamines in a replete person.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

The polyamine branch connects to vitamin B6.

primary_references

A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 102–108

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human and Leishmania ODC comparison; human inhibitor-bound structure. · source_derived_draft · unverified_draft

## arg-odc-cofactor The polyamine branch connects to vitamin B6. Biochemical binding and structural experiments identify PLP as the human ODC coenzyme. Model: Human and Leishmania ODC comparison; human inhibitor-bound structure. Limitations: Cofactor dependence does not establish that extra B6 raises polyamines in a replete person. Evidence access: Primary abstract A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

cell_type

liver-derived enzyme

experimental_model

Enzyme characterization

limitations

Not evidence that extra vitamin B6 improves selenium recycling.

organism

mouse

Selenium: literature corrections and mechanism additions · lines 522–532

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Enzyme characterization · secondary_verified · secondary_verified

## plp-supports-scly-catalysis SCLY uses a vitamin B6-derived cofactor. SCLY is a pyridoxal-phosphate-dependent enzyme. Organism: mouse Cell type: liver-derived enzyme Experimental model: Enzyme characterization Limitations: Not evidence that extra vitamin B6 improves selenium recycling. Primary reference: [cDNA cloning, purification, and characterization of mouse liver selenocysteine lyase. Candidate for selenium delivery protein in selenoprotein synthesis](https://pubmed.ncbi.nlm.nih.gov/10692412/)

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

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

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

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

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

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

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

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

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/

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

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

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

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

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

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

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

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/gaba-research/16491085.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "da61b07cc71e16803fe09321738c7a6c8d2cbac0dff2b189b9f2586ce5950bfa", "start_char": 0, "end_char": 550, "text_sha256": "da61b07cc71e16803fe09321738c7a6c8d2cbac0dff2b189b9f2586ce5950bfa"}

experimental_model

Gene analysis and metabolite measurement in children with pyridoxine-dependent seizures

exposure

Naturally occurring ALDH7A1 mutations abolishing antiquitin dehydrogenase activity

limitations

Human genetics with a defined biochemical consequence. It establishes the chemistry of the cofactor loss; it does not measure brain GABA in the affected children.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human

plain_language

A metabolite that piles up when one enzyme is missing chemically destroys the cofactor a different enzyme needs.

primary_references

[gb-p16491085] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366

tissue_or_cell_type

Whole body

trigger_kind

machinery_impairment Imported condition classification; unverified.

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 118–129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene analysis and metabolite measurement in children with pyridoxine-dependent seizures · source_derived_draft · unverified_draft

### gb-a-metabolite-destroys-the-cofactor Children with pyridoxine-dependent seizures have mutations in the ALDH7A1 gene which encodes antiquitin, these mutations abolish the activity of antiquitin as a delta-1-piperideine-6-carboxylate to alpha-aminoadipic semialdehyde dehydrogenase, the accumulating delta-1-piperideine-6-carboxylate inactivates pyridoxal 5-phosphate by forming a Knoevenagel condensation product, and measurement of urinary alpha-aminoadipic semialdehyde provides a simple way of confirming the diagnosis. Condition category: machinery_impairment nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: A metabolite that piles up when one enzyme is missing chemically destroys the cofactor a different enzyme needs. organism: Human tissue_or_cell_type: Whole body experimental_model: Gene analysis and metabolite measurement in children with pyridoxine-dependent seizures limitations: Human genetics with a defined biochemical consequence. It establishes the chemistry of the cofactor loss; it does not measure brain GABA in the affected children. exposure: Naturally occurring ALDH7A1 mutations abolishing antiquitin dehydrogenase activity evidence_span: {"source_cache": "artifacts/gaba-research/16491085.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "da61b07cc71e16803fe09321738c7a6c8d2cbac0dff2b189b9f2586ce5950bfa", "start_char": 0, "end_char": 550, "text_sha256": "da61b07cc71e16803fe09321738c7a6c8d2cbac0dff2b189b9f2586ce5950bfa"} [gb-p16491085] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

B2-cofactor binding is one part of a broader genetic defect in B6 activation.

evidence_location

Results: Table 3 and Fig 1; Table 2 and Fig 2

experimental_model

Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure.

exposure

Purified-enzyme assay

limitations

Km is a kinetic parameter, not a direct binding constant; adding FMN alone was not shown to normalize this whole defect.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The defect also changes substrate handling and reaction speed.

primary_references

[musayev2009] Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. (2009). https://pubmed.ncbi.nlm.nih.gov/19759001/ DOI: 10.1074/jbc.m109.038372

tissue_or_cell_type

Purified recombinant enzyme; no intact tissue

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1220–1232

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure. · source_derived_draft · unverified_draft

### b2-pnpo-r229w-catalytic-efficiency R229W PNPO showed approximately 850-fold lower PNP catalytic efficiency, combining a 192-fold higher Km and 4.5-fold lower kcat. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect also changes substrate handling and reaction speed. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human wild-type and R229W PNPO; fluorescence titration, kinetics and 2.5-A mutant structure. limitations: Km is a kinetic parameter, not a direct binding constant; adding FMN alone was not shown to normalize this whole defect. exposure: Purified-enzyme assay cross_nutrient: B2-cofactor binding is one part of a broader genetic defect in B6 activation. evidence_location: Results: Table 3 and Fig 1; Table 2 and Fig 2 [musayev2009] Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. (2009). https://pubmed.ncbi.nlm.nih.gov/19759001/ DOI: 10.1074/jbc.m109.038372

evidence_access

Primary abstract

experimental_model

Human KAT-II crystal structure at 1.83 angstrom resolution.

limitations

Cofactor dependence alone does not define clinical B6 requirements or benefit from excess B6.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

Vitamin B6 participates in a branch enzyme, not only the serotonin route.

primary_references

Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 202–208

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human KAT-II crystal structure at 1.83 angstrom resolution. · source_derived_draft · unverified_draft

## tryptophan-kat2-plp Vitamin B6 participates in a branch enzyme, not only the serotonin route. Human KAT-II/AADAT is a PLP-dependent homodimer; the structure shows a PLP–Lys263 aldimine at its catalytic site. Model: Human KAT-II crystal structure at 1.83 angstrom resolution. Limitations: Cofactor dependence alone does not define clinical B6 requirements or benefit from excess B6. Evidence access: Primary abstract Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446

evidence_access

Primary abstract

experimental_model

Cell-free NMR, chromatography and mass-spectrometry experiments motivated by hyperprolinemia type II.

limitations

This demonstrates chemistry under the tested conditions, not B6 depletion from an ordinary proline-containing meal.

nutrient_topic

L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline

plain_language

An accumulating proline intermediate can chemically trap active vitamin B6.

primary_references

Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 118–124

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free NMR, chromatography and mass-spectrometry experiments motivated by hyperprolinemia type II. · source_derived_draft · unverified_draft

## l-proline-p5c-b6-trapping An accumulating proline intermediate can chemically trap active vitamin B6. P5C reacted with pyridoxal phosphate at pH 7.4 and 310 K to form three characterized adducts through condensation involving the PLP aldehyde group. Model: Cell-free NMR, chromatography and mass-spectrometry experiments motivated by hyperprolinemia type II. Limitations: This demonstrates chemistry under the tested conditions, not B6 depletion from an ordinary proline-containing meal. Evidence access: Primary abstract Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200

affected_machinery

ALDH7A1 upstream clearance

availability_state

machinery_impairment Imported condition classification; unverified.

deficiency_not_equivalent

Dietary lysine or vitamin B6 deficiency

experimental_model

Chemical mechanism associated with human ALDH7A1 disease

limitations

Secondary cofactor loss does not demonstrate primary dietary vitamin B6 or lysine deficiency.

organism

Homo sapiens

plain_language

A lysine metabolite can trap active vitamin B6.

primary_references

[mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366

tissue_or_cell_type

PDE-ALDH7A1 biochemical context

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 266–276

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical mechanism associated with human ALDH7A1 disease · source_derived_draft · unverified_draft

### p6c-plp-trapping Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability. Plain language: A lysine metabolite can trap active vitamin B6. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: PDE-ALDH7A1 biochemical context experimental_model: Chemical mechanism associated with human ALDH7A1 disease limitations: Secondary cofactor loss does not demonstrate primary dietary vitamin B6 or lysine deficiency. affected_machinery: ALDH7A1 upstream clearance deficiency_not_equivalent: Dietary lysine or vitamin B6 deficiency [mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366

evidence_span

{"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"}

experimental_model

Crystallography, electron microscopy, kinetics and cell studies

exposure

SDA-complex structural analysis

limitations

Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex

plain_language

The sulfur-supplying machinery for iron-sulfur clusters also uses a vitamin B6-derived cofactor.

primary_references

[iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114

tissue_or_cell_type

Mitochondrial Fe-S assembly machinery

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1148–1159

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, electron microscopy, kinetics and cell studies · source_derived_draft · unverified_draft

### iron-nfs1-plp The NFS1-containing desulfurase complex structure resolved a solvent-exposed PLP cofactor and an unusual substrate-channel architecture. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sulfur-supplying machinery for iron-sulfur clusters also uses a vitamin B6-derived cofactor. organism: Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex tissue_or_cell_type: Mitochondrial Fe-S assembly machinery experimental_model: Crystallography, electron microscopy, kinetics and cell studies limitations: Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested. exposure: SDA-complex structural analysis evidence_span: {"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"} [iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/alcohol-research/27531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98", "start_char": 0, "end_char": 2014, "text_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98"}

experimental_model

Erythrocyte and hepatic experiments isolating acetaldehyde from ethanol

exposure

Acetaldehyde exposure with PLP measurement

limitations

A confirmatory mechanism study attributing the effect specifically to acetaldehyde.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Human and rat material

plain_language

The vitamin damage is done by the metabolite, which is why it tracks with how fast alcohol is oxidised.

primary_references

[alcohol-p27531] The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism. (1978). https://pubmed.ncbi.nlm.nih.gov/27531/ DOI: 10.1172/jci109128

tissue_or_cell_type

Erythrocytes and liver

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 657–668

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocyte and hepatic experiments isolating acetaldehyde from ethanol · source_derived_draft · unverified_draft

### alcohol-acetaldehyde-mediates-b6 Acetaldehyde was shown to mediate the deleterious effect of ethanol on pyridoxal 5-phosphate metabolism. Condition category: nutrient_deficiency nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: The vitamin damage is done by the metabolite, which is why it tracks with how fast alcohol is oxidised. organism: Human and rat material tissue_or_cell_type: Erythrocytes and liver experimental_model: Erythrocyte and hepatic experiments isolating acetaldehyde from ethanol limitations: A confirmatory mechanism study attributing the effect specifically to acetaldehyde. exposure: Acetaldehyde exposure with PLP measurement evidence_span: {"source_cache": "artifacts/alcohol-research/27531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98", "start_char": 0, "end_char": 2014, "text_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98"} [alcohol-p27531] The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism. (1978). https://pubmed.ncbi.nlm.nih.gov/27531/ DOI: 10.1172/jci109128

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/alcohol-research/1168205.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d", "start_char": 0, "end_char": 1391, "text_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d"}

experimental_model

Hepatic PLP metabolism during ethanol oxidation

exposure

Ethanol oxidation with hepatic PLP measurement

limitations

Extends the mechanism to liver. Part of the same series as the erythrocyte work, so the records share a laboratory lineage.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Human and animal liver

plain_language

The same loss shows up in the organ that does the oxidising.

primary_references

[alcohol-p1168205] Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism. (1975). https://pubmed.ncbi.nlm.nih.gov/1168205/ DOI: 10.1172/jci108003

tissue_or_cell_type

Liver

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 670–681

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepatic PLP metabolism during ethanol oxidation · source_derived_draft · unverified_draft

### alcohol-ethanol-oxidation-hepatic-plp The effect of ethanol oxidation on hepatic pyridoxal 5-phosphate metabolism accompanied the plasma changes seen in chronic alcohol abuse. Condition category: nutrient_deficiency nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: The same loss shows up in the organ that does the oxidising. organism: Human and animal liver tissue_or_cell_type: Liver experimental_model: Hepatic PLP metabolism during ethanol oxidation limitations: Extends the mechanism to liver. Part of the same series as the erythrocyte work, so the records share a laboratory lineage. exposure: Ethanol oxidation with hepatic PLP measurement evidence_span: {"source_cache": "artifacts/alcohol-research/1168205.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d", "start_char": 0, "end_char": 1391, "text_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d"} [alcohol-p1168205] Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism. (1975). https://pubmed.ncbi.nlm.nih.gov/1168205/ DOI: 10.1172/jci108003

evidence_access

Primary abstract; reaction-intermediate structural study

experimental_model

Human BCAT2 intermediate structures and established reaction chemistry.

limitations

Reversible enzyme chemistry; concentration and compartment determine net flux.

nutrient_topic

L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine

plain_language

The first breakdown step passes nitrogen to another metabolite.

primary_references

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

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 162–168

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human BCAT2 intermediate structures and established reaction chemistry. · source_derived_draft · unverified_draft

## isoleucine-bcat-reaction The first breakdown step passes nitrogen to another metabolite. Human BCAT2 transfers the isoleucine amino group through the PLP/PMP cycle, linking isoleucine/branched ketoacid interconversion to 2-oxoglutarate/glutamate. Model: Human BCAT2 intermediate structures and established reaction chemistry. Limitations: Reversible enzyme chemistry; concentration and compartment determine net flux. Evidence access: Primary abstract; reaction-intermediate structural study 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

evidence_span

{"source_cache": "artifacts/copper-research/15325682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a", "start_char": 0, "end_char": 1606, "text_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a"}

experimental_model

Long-duration high-copper feeding study

exposure

Nine men; prolonged high copper intake including 7 mg/day supplementation phase

limitations

Small intervention with biomarker outcomes; it does not establish copper as a human methionine-synthase cofactor, B-vitamin depletion, or benefit from high copper intake.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human young men

plain_language

Several vitamin-related blood markers shifted, but that does not identify a new copper-dependent methylation enzyme.

primary_references

[copper-p15325682] Effect of long-term, high-copper intake on the concentrations of plasma homocysteine and B vitamins in young men. (2004). https://pubmed.ncbi.nlm.nih.gov/15325682/ DOI: 10.1016/j.nut.2004.05.011

tissue_or_cell_type

Plasma homocysteine, folate, B12 and PLP

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1183–1194

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Long-duration high-copper feeding study · source_derived_draft · unverified_draft

### copper-copper-homocysteine-folate High copper intake in nine men produced small decreases in plasma homocysteine and folate, without changes in B12 or PLP measures. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several vitamin-related blood markers shifted, but that does not identify a new copper-dependent methylation enzyme. organism: Human young men tissue_or_cell_type: Plasma homocysteine, folate, B12 and PLP experimental_model: Long-duration high-copper feeding study limitations: Small intervention with biomarker outcomes; it does not establish copper as a human methionine-synthase cofactor, B-vitamin depletion, or benefit from high copper intake. exposure: Nine men; prolonged high copper intake including 7 mg/day supplementation phase evidence_span: {"source_cache": "artifacts/copper-research/15325682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a", "start_char": 0, "end_char": 1606, "text_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a"} [copper-p15325682] Effect of long-term, high-copper intake on the concentrations of plasma homocysteine and B vitamins in young men. (2004). https://pubmed.ncbi.nlm.nih.gov/15325682/ DOI: 10.1016/j.nut.2004.05.011

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Purified human disease-associated variant; kinetic and spectroscopic assays.

limitations

Not a dietary B6 or alanine deficiency experiment, and not evidence that either supplement rescues this variant.

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

Having the nutrient available does not guarantee that damaged enzyme machinery can use it.

primary_references

Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 48–54

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human disease-associated variant; kinetic and spectroscopic assays. · source_derived_draft · unverified_draft

## alanine-agt-mutant Having the nutrient available does not guarantee that damaged enzyme machinery can use it. The human AGXT G82E variant retained two PLP molecules per dimer at saturation but had reduced PLP/PMP affinity and about 0.1% of normal overall catalytic activity. Model: Purified human disease-associated variant; kinetic and spectroscopic assays. Limitations: Not a dietary B6 or alanine deficiency experiment, and not evidence that either supplement rescues this variant. Evidence access: Primary abstract Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637

evidence_access

Primary abstract

experimental_model

Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate.

limitations

Cofactor cycling is not evidence that B6 is irreversibly consumed once per reaction.

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

The B6 cofactor changes form while helping transfer nitrogen.

primary_references

Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 40–46

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate. · source_derived_draft · unverified_draft

## alanine-agt-pmp-cycle The B6 cofactor changes form while helping transfer nitrogen. Pre-steady-state analysis of human AGXT showed that PMP remained bound during its catalytic cycle and the AGXT–PMP complex reacted efficiently with oxo-acid substrates. Model: Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate. Limitations: Cofactor cycling is not evidence that B6 is irreversibly consumed once per reaction. Evidence access: Primary abstract Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637

evidence_access

Primary abstract

experimental_model

Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays.

limitations

Peroxisomal enzyme identity does not mean intracellular flux or supplement benefit was measured.

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

Alanine supplies an amino group that turns glyoxylate into glycine.

primary_references

Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18289107/ · DOI 10.2174/092986608783489580

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 32–38

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays. · source_derived_draft · unverified_draft

## alanine-agt-reaction Alanine supplies an amino group that turns glyoxylate into glycine. Purified untagged human AGXT catalyzed the PLP-dependent reaction alanine + glyoxylate ⇌ pyruvate + glycine; forward and reverse kinetic parameters were measured. Model: Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays. Limitations: Peroxisomal enzyme identity does not mean intracellular flux or supplement benefit was measured. Evidence access: Primary abstract Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18289107/ · DOI 10.2174/092986608783489580

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Rat H4IIE cells; siRNA knockdown with alanine challenge.

limitations

Partial knockdown and partial attenuation do not prove ALT1 is the only contributing pathway.

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

The response partly depended on processing alanine, rather than simply sensing it outside the cell.

primary_references

l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 256–262

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat H4IIE cells; siRNA knockdown with alanine challenge. · source_derived_draft · unverified_draft

## alanine-ampk-alt1-dependence The response partly depended on processing alanine, rather than simply sensing it outside the cell. ALT1 siRNA reduced rat H4IIE ALT protein by about 77% and reduced alanine-stimulated AMPK activation by about 49%. Model: Rat H4IIE cells; siRNA knockdown with alanine challenge. Limitations: Partial knockdown and partial attenuation do not prove ALT1 is the only contributing pathway. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse liver Gpt2 genetic deletion; isotope tracing.

limitations

Does not mean GPT2 is the only route; lean knockout animals did not develop a general failure of glucose control. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

Mitochondrial transamination can feed alanine carbon into glucose.

primary_references

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 216–222

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver Gpt2 genetic deletion; isotope tracing. · source_derived_draft · unverified_draft

## alanine-liver-gpt2-flux Mitochondrial transamination can feed alanine carbon into glucose. Hepatocyte-specific Gpt2 deletion reduced labeled alanine contribution to glucose production in mouse hepatocyte experiments. Model: Mouse liver Gpt2 genetic deletion; isotope tracing. Limitations: Does not mean GPT2 is the only route; lean knockout animals did not develop a general failure of glucose control. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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/

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

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

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

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

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

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

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

evidence_access

Primary full text, substrate comparison

experimental_model

Recombinant human enzyme; L-cysteic-acid substrate assays.

limitations

This alternative reaction does not quantify its contribution to human whole-body synthesis.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

The same enzyme can use a more oxidized substrate to make taurine directly.

primary_references

A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 49–55

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme; L-cysteic-acid substrate assays. · source_derived_draft · unverified_draft

## taurine-csad-cysteic-acid The same enzyme can use a more oxidized substrate to make taurine directly. Human CSAD also catalyzed L-cysteic-acid decarboxylation to taurine in vitro. Model: Recombinant human enzyme; L-cysteic-acid substrate assays. Limitations: This alternative reaction does not quantify its contribution to human whole-body synthesis. Evidence access: Primary full text, substrate comparison A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438

evidence_access

Primary full text, introduction and enzyme-assay results

experimental_model

Recombinant human enzyme; substrate kinetics and circular-dichroism assays.

limitations

Hypotaurine still needs oxidation to become taurine; this is not a human supplementation experiment.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

Vitamin B6-dependent CSAD performs a step between cysteine and taurine.

primary_references

A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 33–39

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme; substrate kinetics and circular-dichroism assays. · source_derived_draft · unverified_draft

## taurine-csad-cysteinesulfinate Vitamin B6-dependent CSAD performs a step between cysteine and taurine. Purified human CSAD decarboxylated L-cysteine sulfinic acid to hypotaurine in PLP-containing enzyme assays. Model: Recombinant human enzyme; substrate kinetics and circular-dichroism assays. Limitations: Hypotaurine still needs oxidation to become taurine; this is not a human supplementation experiment. Evidence access: Primary full text, introduction and enzyme-assay results A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438

evidence_span

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experimental_model

Hydrogen-deuterium exchange mass spectrometry, X-ray crystallography and cryo-electron microscopy of the enzyme with a human autoantibody

exposure

Apo and holo forms of GAD65 and the complex with the autoantibody b96.11

limitations

Structural and dynamic work on isolated protein. The conclusion about autoantigenicity is an interpretation of dynamics rather than an immunological measurement.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human protein

plain_language

What makes one of the two enzymes the target of an autoimmune attack is how much it moves, not how its surface reads.

primary_references

[gb-p40055307] Structure and dynamics of GAD65 in complex with an autoimmune polyendocrine syndrome type 2-associated autoantibody. (2025). https://pubmed.ncbi.nlm.nih.gov/40055307/ DOI: 10.1038/s41467-025-57492-4

tissue_or_cell_type

Recombinant enzyme

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 144–155

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hydrogen-deuterium exchange mass spectrometry, X-ray crystallography and cryo-electron microscopy of the enzyme with a human autoantibody · source_derived_draft · unverified_draft

### gb-dynamics-not-sequence-make-the-autoantigen Only GAD65 acts as a major autoantigen, frequently implicated in type 1 diabetes and other autoimmune diseases, hydrogen-deuterium exchange reveals local dynamics accompanying autoinactivation with the catalytic loop promoting collective motions at the C-terminal domain and pyridoxal-5-phosphate domain interface, in the complex with the autoantibody the heavy chain complementarity-determining regions dominate the interaction with a long CDRH3 bridging the GAD65 dimer, and thus intrinsic dynamics rather than sequence differences within epitopes appear to be responsible for the contrasting autoantigenicities of GAD65 and GAD67. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: What makes one of the two enzymes the target of an autoimmune attack is how much it moves, not how its surface reads. organism: Human protein tissue_or_cell_type: Recombinant enzyme experimental_model: Hydrogen-deuterium exchange mass spectrometry, X-ray crystallography and cryo-electron microscopy of the enzyme with a human autoantibody limitations: Structural and dynamic work on isolated protein. The conclusion about autoantigenicity is an interpretation of dynamics rather than an immunological measurement. exposure: Apo and holo forms of GAD65 and the complex with the autoantibody b96.11 evidence_span: {"source_cache": "artifacts/gaba-research/40055307.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "832b0c18514e12230379ef877a5bd017fc67e23d762d3b9f00f5d59dc2f7efe2", "start_char": 0, "end_char": 1448, "text_sha256": "832b0c18514e12230379ef877a5bd017fc67e23d762d3b9f00f5d59dc2f7efe2"} [gb-p40055307] Structure and dynamics of GAD65 in complex with an autoimmune polyendocrine syndrome type 2-associated autoantibody. (2025). https://pubmed.ncbi.nlm.nih.gov/40055307/ DOI: 10.1038/s41467-025-57492-4

evidence_span

{"source_cache": "artifacts/gaba-research/8419527.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de2df4de7da887745f27b7c4593a75590b6de3649a2b5b35a1d36980a86b755", "start_char": 0, "end_char": 1425, "text_sha256": "0de2df4de7da887745f27b7c4593a75590b6de3649a2b5b35a1d36980a86b755"}

experimental_model

Review of the compartments and short-term regulation of brain GABA synthesis

exposure

Glutamate decarboxylase measured as apoenzyme and holoenzyme across brain regions

limitations

A review of the enzymology. The apoenzyme fraction is given for total glutamate decarboxylase, with GAD65 accounting for a substantial majority of it rather than being separately quantified.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Rat and human

plain_language

Half the enzyme is sitting idle without its cofactor, held in reserve for when more transmitter is suddenly needed.

primary_references

[gb-p8419527] Regulation of gamma-aminobutyric acid synthesis in the brain. (1993). https://pubmed.ncbi.nlm.nih.gov/8419527/ DOI: 10.1111/j.1471-4159.1993.tb03165.x

tissue_or_cell_type

Brain

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 105–116

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the compartments and short-term regulation of brain GABA synthesis · source_derived_draft · unverified_draft

### gb-half-the-enzyme-waits At least 50% of glutamate decarboxylase is present in brain as apoenzyme, that is enzyme without bound cofactor, which serves as a reservoir of inactive enzyme that can be drawn on when additional GABA synthesis is needed, a substantial majority of the apoenzyme in brain is accounted for by GAD65 although GAD67 also contributes, the interaction of the enzyme with pyridoxal 5-phosphate is a major factor in the short-term regulation of its activity, and the apparent localization of GAD65 in nerve terminals together with the large reserve of apo-GAD65 suggest that GAD65 is specialized to respond to short-term changes in demand for transmitter GABA. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Half the enzyme is sitting idle without its cofactor, held in reserve for when more transmitter is suddenly needed. organism: Rat and human tissue_or_cell_type: Brain experimental_model: Review of the compartments and short-term regulation of brain GABA synthesis limitations: A review of the enzymology. The apoenzyme fraction is given for total glutamate decarboxylase, with GAD65 accounting for a substantial majority of it rather than being separately quantified. exposure: Glutamate decarboxylase measured as apoenzyme and holoenzyme across brain regions evidence_span: {"source_cache": "artifacts/gaba-research/8419527.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de2df4de7da887745f27b7c4593a75590b6de3649a2b5b35a1d36980a86b755", "start_char": 0, "end_char": 1425, "text_sha256": "0de2df4de7da887745f27b7c4593a75590b6de3649a2b5b35a1d36980a86b755"} [gb-p8419527] Regulation of gamma-aminobutyric acid synthesis in the brain. (1993). https://pubmed.ncbi.nlm.nih.gov/8419527/ DOI: 10.1111/j.1471-4159.1993.tb03165.x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/gaba-research/27086862.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854", "start_char": 0, "end_char": 1299, "text_sha256": "cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854"}

experimental_model

Case report of an infant with a novel homozygous ALPL mutation

exposure

Loss-of-function ALPL mutation with pyridoxine-responsive seizures

limitations

A single case report. It shows the association in one patient and cannot establish how often it occurs or the mechanism by which the cofactor becomes unavailable.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human

plain_language

A child whose alkaline phosphatase does not work had seizures that only pyridoxine controlled.

primary_references

[gb-p27086862] Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene. (2016). https://pubmed.ncbi.nlm.nih.gov/27086862/ DOI: 10.4274/jcrpe.2798

tissue_or_cell_type

Bone and nervous system

trigger_kind

machinery_impairment Imported condition classification; unverified.

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 131–142

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case report of an infant with a novel homozygous ALPL mutation · source_derived_draft · unverified_draft

### gb-losing-the-phosphatase-costs-the-cofactor Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism caused by loss-of-function mutations in the ALPL gene, characterized by defective bone and tooth mineralisation associated with low serum and bone alkaline phosphatase activity, severe forms may present with neurological problems such as seizures, hypotonia and irritability, and here an infantile hypophosphatasia patient presented with pyridoxine-responsive seizures and a novel homozygous mutation in the ALPL gene was detected, with a limited number of such patients in the literature. Condition category: machinery_impairment nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: A child whose alkaline phosphatase does not work had seizures that only pyridoxine controlled. organism: Human tissue_or_cell_type: Bone and nervous system experimental_model: Case report of an infant with a novel homozygous ALPL mutation limitations: A single case report. It shows the association in one patient and cannot establish how often it occurs or the mechanism by which the cofactor becomes unavailable. exposure: Loss-of-function ALPL mutation with pyridoxine-responsive seizures evidence_span: {"source_cache": "artifacts/gaba-research/27086862.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854", "start_char": 0, "end_char": 1299, "text_sha256": "cb18a717a009e567b4480c6826b39f15109745dbb646c752ad66376b6b107854"} [gb-p27086862] Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene. (2016). https://pubmed.ncbi.nlm.nih.gov/27086862/ DOI: 10.4274/jcrpe.2798

evidence_span

{"source_cache": "artifacts/gaba-research/2069816.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d940e6978ff77eeee89607aa24fde9036bb58d013063463389a1ca0cb0eb080", "start_char": 0, "end_char": 738, "text_sha256": "4d940e6978ff77eeee89607aa24fde9036bb58d013063463389a1ca0cb0eb080"}

experimental_model

Molecular and immunological comparison of the two brain forms of the GABA synthetic enzyme

exposure

The two glutamate decarboxylase forms compared for size, sequence, antigenicity, location and cofactor interaction

limitations

A characterisation of two gene products. The pancreatic and autoimmune connections are stated as context rather than measured here.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Rat and human genes

plain_language

There are two versions of the enzyme that makes this transmitter, and they differ in where they sit and how tightly they hold their cofactor.

primary_references

[gb-p2069816] Two genes encode distinct glutamate decarboxylases. (1991). https://pubmed.ncbi.nlm.nih.gov/2069816/ DOI: 10.1016/0896-6273(91)90077-d

tissue_or_cell_type

Brain and pancreas

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 92–103

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Molecular and immunological comparison of the two brain forms of the GABA synthetic enzyme · source_derived_draft · unverified_draft

### gb-two-enzymes-not-one The brain contains two forms of the GABA synthetic enzyme glutamate decarboxylase which differ in molecular size, amino acid sequence, antigenicity, cellular and subcellular location, and interaction with the GAD cofactor pyridoxal phosphate, these forms GAD65 and GAD67 derive from two genes, and their distinctive properties provide a substrate for understanding not only the multiple roles of GABA in the nervous system but also the autoimmune response to GAD in insulin-dependent diabetes mellitus. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: There are two versions of the enzyme that makes this transmitter, and they differ in where they sit and how tightly they hold their cofactor. organism: Rat and human genes tissue_or_cell_type: Brain and pancreas experimental_model: Molecular and immunological comparison of the two brain forms of the GABA synthetic enzyme limitations: A characterisation of two gene products. The pancreatic and autoimmune connections are stated as context rather than measured here. exposure: The two glutamate decarboxylase forms compared for size, sequence, antigenicity, location and cofactor interaction evidence_span: {"source_cache": "artifacts/gaba-research/2069816.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d940e6978ff77eeee89607aa24fde9036bb58d013063463389a1ca0cb0eb080", "start_char": 0, "end_char": 738, "text_sha256": "4d940e6978ff77eeee89607aa24fde9036bb58d013063463389a1ca0cb0eb080"} [gb-p2069816] Two genes encode distinct glutamate decarboxylases. (1991). https://pubmed.ncbi.nlm.nih.gov/2069816/ DOI: 10.1016/0896-6273(91)90077-d

evidence_access

Primary abstract

experimental_model

Human CBS structural study with SAM-bound activated conformation.

limitations

Allosteric regulation does not establish in-vivo flux under every nutritional condition.

nutrient_topic

L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine

plain_language

A plentiful methyl donor can turn up the sulfur-transfer branch.

primary_references

Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25197074/ · DOI 10.1073/pnas.1414545111

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CBS structural study with SAM-bound activated conformation. · source_derived_draft · unverified_draft

## methionine-cbs-sam-allostery A plentiful methyl donor can turn up the sulfur-transfer branch. SAM binding rearranged the human CBS regulatory domain and relieved autoinhibition, improving access to its catalytic pocket. Model: Human CBS structural study with SAM-bound activated conformation. Limitations: Allosteric regulation does not establish in-vivo flux under every nutritional condition. Evidence access: Primary abstract Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25197074/ · DOI 10.1073/pnas.1414545111

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human leukemia cells, knockout and metabolite-rescue experiment.

limitations

Culture rescue is not a nutritional recommendation; this growth endpoint differs from zebrafish hemoglobin.

nutrient_topic

Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Glycine

plain_language

Restoring a downstream one-carbon source worked where adding an amino acid did not.

primary_references

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 122–128

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human leukemia cells, knockout and metabolite-rescue experiment. · source_derived_draft · unverified_draft

## glycine-s38-formate-rescue Restoring a downstream one-carbon source worked where adding an amino acid did not. Formate at 1 mM rescued the low-B6 proliferation defect of SLC25A38-null K562 cells, while glycine, serine and folate did not under the tested conditions. Model: Human leukemia cells, knockout and metabolite-rescue experiment. Limitations: Culture rescue is not a nutritional recommendation; this growth endpoint differs from zebrafish hemoglobin. Evidence access: Primary full text 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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human K562 knockout, isotope tracing and controlled B6 culture conditions.

limitations

Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38.

nutrient_topic

Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Glycine

plain_language

A mitochondrial cofactor problem reduced the cell's ability to make glycine.

primary_references

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 114–120

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human K562 knockout, isotope tracing and controlled B6 culture conditions. · source_derived_draft · unverified_draft

## glycine-s38-glycine-synthesis A mitochondrial cofactor problem reduced the cell's ability to make glycine. SLC25A38 loss reduced deuterated-serine incorporation into glycine and glycine-derived glutathione under low-B6 conditions. Model: Human K562 knockout, isotope tracing and controlled B6 culture conditions. Limitations: Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38. Evidence access: Primary full text 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

cross_nutrient

Separates the B6 phosphorylation step from the B2-dependent oxidation step.

evidence_location

Abstract

experimental_model

Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures.

exposure

Purified-enzyme assay

limitations

This biochemical route does not establish that dietary pyridoxal bypasses all consequences of PNPO disease.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Not every route to active B6 passes through PNPO.

primary_references

[safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107

tissue_or_cell_type

Purified recombinant enzyme; no intact tissue

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1192–1204

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures. · source_derived_draft · unverified_draft

### b2-pdxk-pyridoxal-route Human PDXK assays directly measured ATP-dependent conversion of pyridoxal to PLP, a reaction distinct from PNPO oxidation. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every route to active B6 passes through PNPO. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures. limitations: This biochemical route does not establish that dietary pyridoxal bypasses all consequences of PNPO disease. exposure: Purified-enzyme assay cross_nutrient: Separates the B6 phosphorylation step from the B2-dependent oxidation step. evidence_location: Abstract [safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107

cross_nutrient

A second B6 precursor depends on the FMN enzyme.

evidence_location

Results: kinetic properties; Table 1; FMN-binding structure

experimental_model

Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.

exposure

Purified-enzyme assay

limitations

Biochemical evidence does not establish a dietary threshold or supplementation benefit.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Phosphorylated pyridoxamine enters the same activation enzyme.

primary_references

[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203

tissue_or_cell_type

Purified recombinant enzyme; no intact tissue

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1164–1176

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft

### b2-pnpo-pmp-oxidation Human PNPO also converted PMP to PLP, with a turnover number of 0.20 per second at 37 C. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphorylated pyridoxamine enters the same activation enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: A second B6 precursor depends on the FMN enzyme. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203

cross_nutrient

B2-dependent oxidation activates one B6 precursor.

evidence_location

Results: kinetic properties; Table 1; FMN-binding structure

experimental_model

Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.

exposure

Purified-enzyme assay

limitations

Biochemical evidence does not establish a dietary threshold or supplementation benefit.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

PNPO changes phosphorylated pyridoxine into active B6.

primary_references

[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203

tissue_or_cell_type

Purified recombinant enzyme; no intact tissue

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1150–1162

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft

### b2-pnpo-pnp-oxidation Purified human PNPO converted PNP to PLP with a turnover number of 0.19 per second at 37 C. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PNPO changes phosphorylated pyridoxine into active B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-dependent oxidation activates one B6 precursor. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203

evidence_access

Primary full text, enzyme identification and biochemical assays

experimental_model

Recombinant bacterial enzyme biochemistry.

limitations

Does not establish that B6 supplementation increases this product in humans.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

A bacterial B6-dependent enzyme sends tryptophan down another branch.

primary_references

Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25263219/ · DOI 10.1016/j.chom.2014.09.001

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 546–552

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant bacterial enzyme biochemistry. · source_derived_draft · unverified_draft

## tryptophan-clostridial-tryptamine A bacterial B6-dependent enzyme sends tryptophan down another branch. Purified C. sporogenes CLOSPO_02083 catalyzed tryptophan decarboxylation to tryptamine as a PLP-dependent enzyme. Model: Recombinant bacterial enzyme biochemistry. Limitations: Does not establish that B6 supplementation increases this product in humans. Evidence access: Primary full text, enzyme identification and biochemical assays Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25263219/ · DOI 10.1016/j.chom.2014.09.001

evidence_access

Primary abstract

experimental_model

Human enzyme structural study and catalytic characterization.

limitations

The enzyme performs transamination; it does not directly perform every subsequent chemical rearrangement.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

Kynurenine can be diverted into a neuroactive branch.

primary_references

Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 210–216

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structural study and catalytic characterization. · source_derived_draft · unverified_draft

## tryptophan-kat2-kyna Kynurenine can be diverted into a neuroactive branch. Human KAT-II transaminates kynurenine to an intermediate that leads to kynurenic acid. Model: Human enzyme structural study and catalytic characterization. Limitations: The enzyme performs transamination; it does not directly perform every subsequent chemical rearrangement. Evidence access: Primary abstract Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446

evidence_access

Primary full text, enzyme screening and purification

experimental_model

Purified bacterial enzyme assays.

limitations

Enzyme presence and activity are not universal across human gut communities.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

Different microbes can reach the same metabolite with distinct proteins.

primary_references

Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25263219/ · DOI 10.1016/j.chom.2014.09.001

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 554–560

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial enzyme assays. · source_derived_draft · unverified_draft

## tryptophan-ruminococcal-tryptamine Different microbes can reach the same metabolite with distinct proteins. Purified R. gnavus RUMGNA_01526 robustly decarboxylated tryptophan despite only 26% sequence identity to the C. sporogenes enzyme. Model: Purified bacterial enzyme assays. Limitations: Enzyme presence and activity are not universal across human gut communities. Evidence access: Primary full text, enzyme screening and purification Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25263219/ · DOI 10.1016/j.chom.2014.09.001

evidence_access

Primary full text, Figure 2

experimental_model

Purified E. coli enzyme and tnaA-mutant experiments.

limitations

5-HTP and tryptophan are distinct substrates, not interchangeable supplement exposures.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

The serotonin precursor can instead become a microbial product.

primary_references

Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33481771/ · DOI 10.1371/journal.pbio.3001070

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 642–648

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified E. coli enzyme and tnaA-mutant experiments. · source_derived_draft · unverified_draft

## tryptophan-tnaa-hydroxyindole The serotonin precursor can instead become a microbial product. TnaA also converted 5-HTP to 5-hydroxyindole, with lower catalytic efficiency than for tryptophan. Model: Purified E. coli enzyme and tnaA-mutant experiments. Limitations: 5-HTP and tryptophan are distinct substrates, not interchangeable supplement exposures. Evidence access: Primary full text, Figure 2 Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33481771/ · DOI 10.1371/journal.pbio.3001070

evidence_access

Primary full text, Figure 2 and enzyme-kinetics methods

experimental_model

Purified bacterial enzyme kinetics.

limitations

Culture kinetics do not predict a person’s production rate.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

A bacterial enzyme creates the indole that can enter host liver metabolism.

primary_references

Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33481771/ · DOI 10.1371/journal.pbio.3001070

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 634–640

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial enzyme kinetics. · source_derived_draft · unverified_draft

## tryptophan-tnaa-indole A bacterial enzyme creates the indole that can enter host liver metabolism. Purified E. coli BW25113 TnaA converted L-tryptophan to indole in a PLP-containing assay; tryptophan Km was 0.19 ± 0.009 mM. Model: Purified bacterial enzyme kinetics. Limitations: Culture kinetics do not predict a person’s production rate. Evidence access: Primary full text, Figure 2 and enzyme-kinetics methods Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33481771/ · DOI 10.1371/journal.pbio.3001070

evidence_access

Primary abstract

experimental_model

Gut bacterial enzyme/substrate characterization.

limitations

This is bacterial metabolism, distinct from human DDC. Tyramine exposure from food is not equivalent to free tyrosine intake.

nutrient_topic

L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine

plain_language

Microbes can divert the amino acid into a bioactive amine.

primary_references

Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30659181/ · DOI 10.1038/s41467-019-08294-y

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 332–338

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Gut bacterial enzyme/substrate characterization. · source_derived_draft · unverified_draft

## l-tyrosine-bacterial-tyramine Microbes can divert the amino acid into a bioactive amine. Gut bacterial tyrosine decarboxylase accepts tyrosine and also decarboxylates levodopa. Model: Gut bacterial enzyme/substrate characterization. Limitations: This is bacterial metabolism, distinct from human DDC. Tyramine exposure from food is not equivalent to free tyrosine intake. Evidence access: Primary abstract Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30659181/ · DOI 10.1038/s41467-019-08294-y

evidence_access

Primary abstract

experimental_model

Purified full-length and truncated human enzyme expressed in E. coli.

limitations

A reversible enzyme assay is not a measurement of net in vivo flux.

nutrient_topic

L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine

plain_language

Tyrosine breakdown begins by moving its amino group.

primary_references

The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified full-length and truncated human enzyme expressed in E. coli. · source_derived_draft · unverified_draft

## l-tyrosine-tat-carbon Tyrosine breakdown begins by moving its amino group. Recombinant human TAT catalyzed reversible tyrosine transamination, with the highest activity for the tyrosine/2-oxoglutarate substrate pair. Model: Purified full-length and truncated human enzyme expressed in E. coli. Limitations: A reversible enzyme assay is not a measurement of net in vivo flux. Evidence access: Primary abstract The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x

evidence_access

Primary full text

experimental_model

Recombinant human PSAT kinetics and substrate-bound crystal structures.

limitations

This is an enzyme reaction, not evidence that dietary glutamate or B6 is limiting in a particular person.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

Glutamate supplies nitrogen while active B6 enables the transfer.

primary_references

L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 30–36

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human PSAT kinetics and substrate-bound crystal structures. · source_derived_draft · unverified_draft

## l-serine-psat-nitrogen Glutamate supplies nitrogen while active B6 enables the transfer. Human PSAT1 transfers nitrogen from glutamate to phosphohydroxypyruvate, producing O-phosphoserine and 2-oxoglutarate in a reversible PLP-dependent reaction. Model: Recombinant human PSAT kinetics and substrate-bound crystal structures. Limitations: This is an enzyme reaction, not evidence that dietary glutamate or B6 is limiting in a particular person. Evidence access: Primary full text L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609

evidence_access

Primary abstract

experimental_model

Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure.

limitations

Enzyme capacity does not quantify its share of whole-body serine disposal.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

Serine carbon can enter central metabolism through a B6-dependent breakdown step.

primary_references

Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15689518/ · DOI 10.1110/ps.041179105

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 366–372

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure. · source_derived_draft · unverified_draft

## l-serine-sds-catabolism Serine carbon can enter central metabolism through a B6-dependent breakdown step. Human liver serine dehydratase uses PLP to convert L-serine to pyruvate and ammonia; its active holoenzyme was structurally characterized. Model: Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure. Limitations: Enzyme capacity does not quantify its share of whole-body serine disposal. Evidence access: Primary abstract Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15689518/ · DOI 10.1110/ps.041179105

evidence_access

Primary abstract

experimental_model

Recombinant human enzymes, 2.8-angstrom SDSL structure and site-directed mutagenesis.

limitations

This is a comparison of enzyme constructs, not clinical evidence of a dietary shortage.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

Related enzymes are not interchangeable just because they use the same substrate.

primary_references

A catalytic mechanism that explains a low catalytic activity of serine dehydratase like-1 from human cancer cells: crystal structure and site-directed mutagenesis studies. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18342636/ · DOI 10.1016/j.bbagen.2008.01.020

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 374–380

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzymes, 2.8-angstrom SDSL structure and site-directed mutagenesis. · source_derived_draft · unverified_draft

## l-serine-sdsl-distinction Related enzymes are not interchangeable just because they use the same substrate. Human serine dehydratase-like protein had lower activity than the hepatic enzyme; structures and complementary mutations implicated active-site differences, including Gly72. Model: Recombinant human enzymes, 2.8-angstrom SDSL structure and site-directed mutagenesis. Limitations: This is a comparison of enzyme constructs, not clinical evidence of a dietary shortage. Evidence access: Primary abstract A catalytic mechanism that explains a low catalytic activity of serine dehydratase like-1 from human cancer cells: crystal structure and site-directed mutagenesis studies. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18342636/ · DOI 10.1016/j.bbagen.2008.01.020

evidence_access

Primary abstract

experimental_model

Human SepSecS–tRNA complex structure with enzyme assays.

limitations

Free phosphoserine and a phosphoserine residue on this specialized tRNA are not interchangeable substrates.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

The carrier and the cofactor are part of the reaction, not optional packaging.

primary_references

The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19608919/ · DOI 10.1126/science.1173755

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 390–396

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SepSecS–tRNA complex structure with enzyme assays. · source_derived_draft · unverified_draft

## l-serine-sepsecs-substrate The carrier and the cofactor are part of the reaction, not optional packaging. Human SepSecS structural and functional analysis supported correct positioning of tRNA-bound phosphoserine, but not free phosphoserine, for PLP-dependent selenocysteine formation. Model: Human SepSecS–tRNA complex structure with enzyme assays. Limitations: Free phosphoserine and a phosphoserine residue on this specialized tRNA are not interchangeable substrates. Evidence access: Primary abstract The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19608919/ · DOI 10.1126/science.1173755

evidence_access

Primary abstract

experimental_model

Recombinant human serine racemase and serine dehydratase mutants with functional comparisons.

limitations

Engineered reaction switching does not mean the native enzymes have identical functions.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

One enzyme creates the D-form used in a distinct signaling pathway.

primary_references

Modulating the function of human serine racemase and human serine dehydratase by protein engineering. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23112234/ · DOI 10.1093/protein/gzs078

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 406–412

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human serine racemase and serine dehydratase mutants with functional comparisons. · source_derived_draft · unverified_draft

## l-serine-srr-racemization One enzyme creates the D-form used in a distinct signaling pathway. Human serine racemase catalyzes the PLP-dependent formation of D-serine from L-serine; replacing Ser84 with alanine shifted its behavior toward serine dehydratase activity. Model: Recombinant human serine racemase and serine dehydratase mutants with functional comparisons. Limitations: Engineered reaction switching does not mean the native enzymes have identical functions. Evidence access: Primary abstract Modulating the function of human serine racemase and human serine dehydratase by protein engineering. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23112234/ · DOI 10.1093/protein/gzs078

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human index-case context combined with in-vitro chemical mechanism.

limitations

Contribution to seizures is an interpretation; the paper does not establish controlled efficacy or a universal treatment dose.

nutrient_topic

L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline

plain_language

A breakdown disorder can create a secondary cofactor problem.

primary_references

Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 126–132

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human index-case context combined with in-vitro chemical mechanism. · source_derived_draft · unverified_draft

## l-proline-p5c-clinical-link A breakdown disorder can create a secondary cofactor problem. The study was prompted by B6 deficiency and seizures in a child with hyperprolinemia type II; the adduct experiments support P5C-mediated cofactor inactivation as a contributing mechanism. Model: Human index-case context combined with in-vitro chemical mechanism. Limitations: Contribution to seizures is an interpretation; the paper does not establish controlled efficacy or a universal treatment dose. Evidence access: Primary abstract Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

exposure

Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract.

limitations

Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation.

nutrient_topic

Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc

organism

Cell species not specified in abstract

plain_language

Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins.

primary_references

[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

tissue_or_cell_type

Cultured-cell membrane lysates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 833–844

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft

### zinc-enz-bvitamin-cell-hydrolysis Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins. organism: Cell species not specified in abstract tissue_or_cell_type: Cultured-cell membrane lysates experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. exposure: Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

evidence_access

Primary abstract

experimental_model

Human recombinant enzymes expressed in E. coli and compared biochemically.

limitations

Activity in a purified system does not quantify whole-body human threonine flux. The threonine product is alpha-ketobutyrate, distinct from the serine product pyruvate.

nutrient_topic

L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine

plain_language

Threonine can enter carbon metabolism through an enzyme it shares with serine.

primary_references

Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 250–256

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant enzymes expressed in E. coli and compared biochemically. · source_derived_draft · unverified_draft

## l-threonine-human-sds-catabolism Threonine can enter carbon metabolism through an enzyme it shares with serine. Purified human hepatic serine dehydratase showed L-threonine dehydratase activity in comparison with the human SDH-like isoform. Model: Human recombinant enzymes expressed in E. coli and compared biochemically. Limitations: Activity in a purified system does not quantify whole-body human threonine flux. The threonine product is alpha-ketobutyrate, distinct from the serine product pyruvate. Evidence access: Primary abstract Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

evidence_access

Primary abstract

experimental_model

Comparative human enzyme kinetics and PLP-binding measurements.

limitations

Isoform abundance in cultured cells was low; catalytic capacity does not establish its dominant tissue role.

nutrient_topic

L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine

plain_language

Closely related enzymes can process the same substrate at different rates.

primary_references

Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 258–264

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Comparative human enzyme kinetics and PLP-binding measurements. · source_derived_draft · unverified_draft

## l-threonine-human-sdsl-catabolism Closely related enzymes can process the same substrate at different rates. The recombinant human SDH-like protein also had threonine dehydratase activity, with kinetic constants differing substantially from hepatic SDS. Model: Comparative human enzyme kinetics and PLP-binding measurements. Limitations: Isoform abundance in cultured cells was low; catalytic capacity does not establish its dominant tissue role. Evidence access: Primary abstract Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293T knockout/rescue and LC–MS/MS persulfide assays.

limitations

Assay and mutation-dependent evidence; the proposed importance of this route is not proof of identical dominance in all human tissues.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

One enzyme had separable roles in protein synthesis and sulfur chemistry.

primary_references

Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 164–170

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T knockout/rescue and LC–MS/MS persulfide assays. · source_derived_draft · unverified_draft

## l-cysteine-cars2-persulfide One enzyme had separable roles in protein synthesis and sulfur chemistry. CARS2 disruption lowered cysteine-persulfide production in human cells, and wild-type or the C78/257D mutant restored it despite differing effects on translation. Model: Human HEK293T knockout/rescue and LC–MS/MS persulfide assays. Limitations: Assay and mutation-dependent evidence; the proposed importance of this route is not proof of identical dominance in all human tissues. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

evidence_access

Primary abstract

experimental_model

Human and yeast CBS kinetics, with human enzyme kept as this record’s subject.

limitations

Relative pathway dominance in a tissue cannot be read directly from purified-enzyme substrate tests.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

An enzyme that helps synthesize cysteine can also use it in sulfur-gas production.

primary_references

Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 284–290

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and yeast CBS kinetics, with human enzyme kept as this record’s subject. · source_derived_draft · unverified_draft

## l-cysteine-cbs-h2s-branch An enzyme that helps synthesize cysteine can also use it in sulfur-gas production. Purified human CBS favored H2S production through replacement of cysteine by homocysteine over the tested alternative cysteine reactions. Model: Human and yeast CBS kinetics, with human enzyme kept as this record’s subject. Limitations: Relative pathway dominance in a tissue cannot be read directly from purified-enzyme substrate tests. Evidence access: Primary abstract Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293 metabolic tracing and enzyme perturbation.

limitations

Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

An internal synthesis route compensated when imported cystine was harder to use.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 76–82

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 metabolic tracing and enzyme perturbation. · source_derived_draft · unverified_draft

## l-cysteine-trp14-compensation An internal synthesis route compensated when imported cystine was harder to use. TXNDC17 knockout shifted human-cell cysteine supply toward transsulfuration, as assessed using labeled methionine and downstream sulfur metabolites. Model: Human HEK293 metabolic tracing and enzyme perturbation. Limitations: Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

evidence_span

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experimental_model

Recombinant enzyme crystal structure

exposure

PLP-bound enzyme structure

limitations

The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human OAT

plain_language

This is an ornithine-processing reaction; its direction depends on the biological setting.

primary_references

[citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

tissue_or_cell_type

Mitochondrial ornithine transamination

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 346–357

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme crystal structure · source_derived_draft · unverified_draft

### citrulline-oat-reaction OAT transfers the ornithine delta-amino group to 2-oxoglutarate, yielding glutamate and glutamate semialdehyde, which cyclizes to P5C. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is an ornithine-processing reaction; its direction depends on the biological setting. organism: Human OAT tissue_or_cell_type: Mitochondrial ornithine transamination experimental_model: Recombinant enzyme crystal structure limitations: The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine. exposure: PLP-bound enzyme structure evidence_span: {"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"} [citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

experimental_model

Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography

limitations

AADAT also accepts other substrates; substrate breadth is not lysine-specific regulation.

organism

Homo sapiens

plain_language

AADAT removes the remaining amino group.

primary_references

[goh2002] Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). (2002). https://pubmed.ncbi.nlm.nih.gov/12126930/ DOI: 10.1016/S1096-7192(02)00037-9 [han2008] Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2559858/ DOI: 10.1042/BSR20080085

tissue_or_cell_type

Mitochondrial lysine catabolism; human expression highest in liver in cloning study

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 114–123

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography · source_derived_draft · unverified_draft

### aadat-transamination PLP-dependent AADAT transfers the amino group from aminoadipate to 2-oxoglutarate, generating 2-oxoadipate and glutamate. Plain language: AADAT removes the remaining amino group. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial lysine catabolism; human expression highest in liver in cloning study experimental_model: Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography limitations: AADAT also accepts other substrates; substrate breadth is not lysine-specific regulation. [goh2002] Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). (2002). https://pubmed.ncbi.nlm.nih.gov/12126930/ DOI: 10.1016/S1096-7192(02)00037-9 [han2008] Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2559858/ DOI: 10.1042/BSR20080085

experimental_model

E. coli inducible lysine decarboxylase structural and acid-stress experiments.

limitations

Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism.

organism

Escherichia coli

plain_language

Some bacteria use lysine to buffer acidic conditions.

primary_references

[cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 618–626

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · E. coli inducible lysine decarboxylase structural and acid-stress experiments. · source_derived_draft · unverified_draft

### bacterial-cada-decarboxylation E. coli CadA converts lysine to cadaverine and CO2 while consuming a proton during acid stress. Plain language: Some bacteria use lysine to buffer acidic conditions. Condition category: normal organism: Escherichia coli tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: E. coli inducible lysine decarboxylase structural and acid-stress experiments. limitations: Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism. [cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

experimental_model

Purified human enzyme; NMR and coupled activity assays

limitations

Whole-body flux contribution remains unquantified.

organism

Homo sapiens

plain_language

SHMT1 can perform the second carnitine-synthesis reaction.

primary_references

[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

tissue_or_cell_type

Cytosolic enzyme tested in vitro

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 177–185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme; NMR and coupled activity assays · source_derived_draft · unverified_draft

### shmt1-html-cleavage Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine. Plain language: SHMT1 can perform the second carnitine-synthesis reaction. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic enzyme tested in vitro experimental_model: Purified human enzyme; NMR and coupled activity assays limitations: Whole-body flux contribution remains unquantified. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

experimental_model

Purified human enzyme kinetic assay

limitations

Mouse Tha1 specialization should not be assigned to a human THA1 enzyme.

organism

Homo sapiens

plain_language

SHMT2 provides another demonstrated aldolase activity.

primary_references

[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

tissue_or_cell_type

Mitochondrial enzyme tested in vitro

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 187–195

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme kinetic assay · source_derived_draft · unverified_draft

### shmt2-html-cleavage Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1. Plain language: SHMT2 provides another demonstrated aldolase activity. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial enzyme tested in vitro experimental_model: Purified human enzyme kinetic assay limitations: Mouse Tha1 specialization should not be assigned to a human THA1 enzyme. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"}

experimental_model

Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay

exposure

PLP quantification, cysteine desulfurase assays and Moco/MPT binding

limitations

Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Human genetics and human MOCOS proteins; plant XDH variant experiment separately

plain_language

Having some B6 cofactor bound did not repair the defective enzyme.

primary_references

[mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788

tissue_or_cell_type

Patient samples and purified domains

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 547–558

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay · source_derived_draft · unverified_draft

### mo-mocos-t349i The Thr349Ile MOCOS N-terminal domain had severely impaired cysteine desulfurase activity, including a preparation with measurable PLP binding. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having some B6 cofactor bound did not repair the defective enzyme. organism: Human genetics and human MOCOS proteins; plant XDH variant experiment separately tissue_or_cell_type: Patient samples and purified domains experimental_model: Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay limitations: Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains. exposure: PLP quantification, cysteine desulfurase assays and Moco/MPT binding evidence_span: {"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"} [mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human proliferating cell models; genetic screen and metabolic tracing during ETC inhibition.

limitations

Direction is conditional, not an intrinsic one-way label for GOT1.

nutrient_topic

L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate

plain_language

A reversible enzyme can run in a different direction when the cell’s redox state changes.

primary_references

An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 50–56

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human proliferating cell models; genetic screen and metabolic tracing during ETC inhibition. · source_derived_draft · unverified_draft

## l-aspartate-got1-reversal A reversible enzyme can run in a different direction when the cell’s redox state changes. Under electron-transport-chain inhibition, human GOT1 supported cytosolic aspartate synthesis rather than its usual aspartate-consuming shuttle direction. Model: Human proliferating cell models; genetic screen and metabolic tracing during ETC inhibition. Limitations: Direction is conditional, not an intrinsic one-way label for GOT1. Evidence access: Primary full text An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016

cross_nutrient

Links existing B6-dependent SHMT chemistry to folate flux direction.

experimental_model

Stable-isotope tracing

exposure

Assay conditions described in the linked primary study.

limitations

Not a universal direction across tissues or nutrition states.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Homo sapiens

plain_language

SHMT1 can consume one-carbon units instead of producing them.

primary_references

[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016

tissue_or_cell_type

HEK293T and HCT116 cells

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 923–934

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracing · source_derived_draft · unverified_draft

### shmt1-reverse-flux-replete In nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: SHMT1 can consume one-carbon units instead of producing them. organism: Homo sapiens tissue_or_cell_type: HEK293T and HCT116 cells experimental_model: Stable-isotope tracing limitations: Not a universal direction across tissues or nutrition states. exposure: Assay conditions described in the linked primary study. cross_nutrient: Links existing B6-dependent SHMT chemistry to folate flux direction. [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016

cross_nutrient

true

evidence_location

Abstract; primary Results: Identification of the ACP–Lipid–ISD11 Motif

experimental_model

Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure

exposure

Coexpression and structural analysis; no nutrient restriction.

limitations

This is not an all-human ACP structure. The bound PLP and acyl-ACP show cofactor coexistence; dietary B6/B5 dependency or repletion was not tested. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens proteins; Escherichia coli ACP

plain_language

The CoA-derived carrier arm holds a fatty-acid chain that helps form the iron–sulfur complex interface.

primary_references

[b5-met-cory2017] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114

tissue_or_cell_type

Purified recombinant Fe–S assembly subcomplex

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 935–947

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure · source_derived_draft · unverified_draft

### b5-met-acyl-acp-isd11-interface In the recombinant hybrid NFS1–ISD11–ACP structure, the phosphopantetheine-linked acyl group of E. coli ACP occupies the hydrophobic core of human ISD11. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoA-derived carrier arm holds a fatty-acid chain that helps form the iron–sulfur complex interface. organism: Homo sapiens proteins; Escherichia coli ACP tissue_or_cell_type: Purified recombinant Fe–S assembly subcomplex experimental_model: Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure limitations: This is not an all-human ACP structure. The bound PLP and acyl-ACP show cofactor coexistence; dietary B6/B5 dependency or repletion was not tested. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Coexpression and structural analysis; no nutrient restriction. cross_nutrient: true evidence_location: Abstract; primary Results: Identification of the ACP–Lipid–ISD11 Motif [b5-met-cory2017] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/alcohol-research/4359937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08", "start_char": 0, "end_char": 1650, "text_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08"}

experimental_model

Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays

exposure

Chronic alcohol abuse; acetaldehyde and ethanol applied to erythrocytes

limitations

Selecting subjects without abnormal liver function isolates the vitamin effect from liver disease. The phosphatase mechanism is shown in erythrocytes, not liver.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Human

plain_language

More than half had less of the active vitamin than any healthy control, with healthy livers.

primary_references

[alcohol-p4359937] Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. (1974). https://pubmed.ncbi.nlm.nih.gov/4359937/ DOI: 10.1172/jci107607

tissue_or_cell_type

Plasma and erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 631–642

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays · source_derived_draft · unverified_draft

### alcohol-low-plp-prevalence Thirty-five of 66 alcoholic subjects selected for normal liver function and haematology had plasma PLP below 5 ng/ml, the lowest value found in 94 controls. Condition category: nutrient_deficiency nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: More than half had less of the active vitamin than any healthy control, with healthy livers. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays limitations: Selecting subjects without abnormal liver function isolates the vitamin effect from liver disease. The phosphatase mechanism is shown in erythrocytes, not liver. exposure: Chronic alcohol abuse; acetaldehyde and ethanol applied to erythrocytes evidence_span: {"source_cache": "artifacts/alcohol-research/4359937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08", "start_char": 0, "end_char": 1650, "text_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08"} [alcohol-p4359937] Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. (1974). https://pubmed.ncbi.nlm.nih.gov/4359937/ DOI: 10.1172/jci107607

evidence_access

Primary abstract

experimental_model

Recombinant human OAT structure and described catalytic reaction.

limitations

Reversible pathway; net flux depends on tissue and substrate conditions.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

Ornithine also feeds a pathway connected to proline metabolism.

primary_references

Crystal structure of human recombinant ornithine aminotransferase. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9514741/ · DOI 10.1006/jmbi.1997.1583

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 118–124

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human OAT structure and described catalytic reaction. · source_derived_draft · unverified_draft

## arg-oat-reaction Ornithine also feeds a pathway connected to proline metabolism. OAT transfers the ornithine delta-amino group to 2-oxoglutarate, producing glutamate-5-semialdehyde and glutamate. Model: Recombinant human OAT structure and described catalytic reaction. Limitations: Reversible pathway; net flux depends on tissue and substrate conditions. Evidence access: Primary abstract Crystal structure of human recombinant ornithine aminotransferase. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9514741/ · DOI 10.1006/jmbi.1997.1583

evidence_access

Primary abstract and indexed primary full-text introduction, PMC1904517

experimental_model

Human ODC study; reaction identified in the primary paper introduction.

limitations

Reaction identity does not establish net pathway flux after supplementation.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

This reaction opens the polyamine branch.

primary_references

A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 110–116

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human ODC study; reaction identified in the primary paper introduction. · source_derived_draft · unverified_draft

## arg-odc-reaction This reaction opens the polyamine branch. ODC catalyzes conversion of ornithine into putrescine. Model: Human ODC study; reaction identified in the primary paper introduction. Limitations: Reaction identity does not establish net pathway flux after supplementation. Evidence access: Primary abstract and indexed primary full-text introduction, PMC1904517 A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

cell_type

liver-derived enzyme

experimental_model

Purified and recombinant enzyme

limitations

The original assay described elemental selenium; intracellular speciation remains separate.

organism

mouse

Selenium: literature corrections and mechanism additions · lines 510–520

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Purified and recombinant enzyme · secondary_verified · secondary_verified

## scly-decomposes-selenocysteine SCLY recovers selenium from free selenocysteine. SCLY decomposes free L-selenocysteine, yielding L-alanine and released selenium. Organism: mouse Cell type: liver-derived enzyme Experimental model: Purified and recombinant enzyme Limitations: The original assay described elemental selenium; intracellular speciation remains separate. Primary reference: [cDNA cloning, purification, and characterization of mouse liver selenocysteine lyase. Candidate for selenium delivery protein in selenoprotein synthesis](https://pubmed.ncbi.nlm.nih.gov/10692412/)