NADH

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}]

experimental_model

Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.

exposure

NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays.

limitations

Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH.

nutrient_topic

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

organism

Bos taurus

plain_language

An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.

primary_references

[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

tissue_or_cell_type

Heart submitochondrial particles

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 583–594

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft

### b2-met-complex-i-reductive-fmn-loss NADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH. exposure: NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

dose

Tartrazine among tested substrates; exact substrate/cofactor concentrations unavailable in abstract

duration

Assay interval unavailable in primary abstract

evidence_access

Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Purified Escherichia coli K12 azoreductases I and II

limitations

Both NADH and NADPH served as electron donors in enzyme characterization. This does not prove that niacin intake controls dye metabolism in humans. Protein genes and tartrazine-specific kinetic constants are unresolved.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Purified Escherichia coli K12 azoreductases I and II

plain_language

NADH functioned as an electron donor for the purified azoreductases characterized with an azo-dye substrate panel including tartrazine.

primary_references

Purification of two azoreductases from Escherichia coli K12. (1993). https://pubmed.ncbi.nlm.nih.gov/8112774/

route

In vitro enzyme/substrate incubation

tissue

Cell-free azo-reduction assays

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 39–48

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Purified Escherichia coli K12 azoreductases I and II · source_derived_draft · unverified_draft

## tartrazine-nadh-donor NADH functioned as an electron donor for the purified azoreductases characterized with an azo-dye substrate panel including tartrazine. Model/species: Purified Escherichia coli K12 azoreductases I and II Tissue: Cell-free azo-reduction assays Exposure: Tartrazine among tested substrates; exact substrate/cofactor concentrations unavailable in abstract Route: In vitro enzyme/substrate incubation Duration: Assay interval unavailable in primary abstract Limits: Both NADH and NADPH served as electron donors in enzyme characterization. This does not prove that niacin intake controls dye metabolism in humans. Protein genes and tartrazine-specific kinetic constants are unresolved. Primary reference: Purification of two azoreductases from Escherichia coli K12. (1993). https://pubmed.ncbi.nlm.nih.gov/8112774/ Access: Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_span

{"source_cache": "artifacts/boron-research/12827632.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7c91724a5710f61e1907669a1137b421e1e13117ae707e567bd16ca0eea9ed6", "start_char": 0, "end_char": 1255, "text_sha256": "a7c91724a5710f61e1907669a1137b421e1e13117ae707e567bd16ca0eea9ed6"}

experimental_model

Electrospray mass spectrometry and boron-11 NMR

exposure

NAD+/NADH with boric acid or borate across pH conditions; complexes detected at 50 µM each at pH 7

limitations

Chemical structure experiments do not establish cellular concentrations or physiological consequences.

nutrient_topic

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

organism

Cell-free chemistry

plain_language

Oxidized and reduced NAD do not necessarily make the same boron complexes.

primary_references

[boron-p12827632] Esterification of borate with NAD+ and NADH as studied by electrospray ionization mass spectrometry and 11B NMR spectroscopy. (2003). https://pubmed.ncbi.nlm.nih.gov/12827632/ DOI: 10.1002/jms.476

tissue_or_cell_type

Purified nucleotide solutions

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 131–142

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrospray mass spectrometry and boron-11 NMR · source_derived_draft · unverified_draft

### boron-nadh-adduct-structure NADH formed a monoester boron adduct in the analyzed solutions, whereas the additional diester and diborate forms observed for NAD+ were not detected for NADH. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidized and reduced NAD do not necessarily make the same boron complexes. organism: Cell-free chemistry tissue_or_cell_type: Purified nucleotide solutions experimental_model: Electrospray mass spectrometry and boron-11 NMR limitations: Chemical structure experiments do not establish cellular concentrations or physiological consequences. exposure: NAD+/NADH with boric acid or borate across pH conditions; complexes detected at 50 µM each at pH 7 evidence_span: {"source_cache": "artifacts/boron-research/12827632.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7c91724a5710f61e1907669a1137b421e1e13117ae707e567bd16ca0eea9ed6", "start_char": 0, "end_char": 1255, "text_sha256": "a7c91724a5710f61e1907669a1137b421e1e13117ae707e567bd16ca0eea9ed6"} [boron-p12827632] Esterification of borate with NAD+ and NADH as studied by electrospray ionization mass spectrometry and 11B NMR spectroscopy. (2003). https://pubmed.ncbi.nlm.nih.gov/12827632/ DOI: 10.1002/jms.476

evidence_span

{"source_cache": "artifacts/lycopene-research/16672231.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445", "start_char": 0, "end_char": 1967, "text_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445"}

experimental_model

Recombinant ferret enzyme and tissue-fraction metabolism

exposure

5-cis, 13-cis and all-trans lycopene; iron; NAD+ or NADH

limitations

Ferret experiments do not quantify human cleavage flux or predict supplement response.

nutrient_topic

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

organism

Ferret

plain_language

The reduced form of the cofactor instead supported an alcohol product.

primary_references

[lycopene-p16672231] The biochemical characterization of ferret carotene-9',10'-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. (2006). https://pubmed.ncbi.nlm.nih.gov/16672231/ DOI: 10.1074/jbc.m512095200

tissue_or_cell_type

BCO2 enzyme; hepatic fractions and lung

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 351–362

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

### lycopene-apo-nadh NADH supported conversion of apo-10-prime-lycopenal to apo-10-prime-lycopenol in ferret hepatic fractions. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reduced form of the cofactor instead supported an alcohol product. organism: Ferret tissue_or_cell_type: BCO2 enzyme; hepatic fractions and lung experimental_model: Recombinant ferret enzyme and tissue-fraction metabolism limitations: Ferret experiments do not quantify human cleavage flux or predict supplement response. exposure: 5-cis, 13-cis and all-trans lycopene; iron; NAD+ or NADH evidence_span: {"source_cache": "artifacts/lycopene-research/16672231.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445", "start_char": 0, "end_char": 1967, "text_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445"} [lycopene-p16672231] The biochemical characterization of ferret carotene-9',10'-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. (2006). https://pubmed.ncbi.nlm.nih.gov/16672231/ DOI: 10.1074/jbc.m512095200

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats

exposure

Control and selenium-deficient rat liver microsome assays

limitations

Responsible microsomal enzyme was not established in the abstract; do not assign the activity to TXNRD1.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

A membrane-associated recycling route remained active despite selenium shortage.

primary_references

[may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039

tissue_or_cell_type

Liver microsomal fraction

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 442–453

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats · source_derived_draft · unverified_draft

### vc-transport-microsomal-radical Rat liver microsomes reduced ascorbyl radical using NADH, and this activity was insensitive to selenium depletion. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane-associated recycling route remained active despite selenium shortage. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal fraction experimental_model: Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats limitations: Responsible microsomal enzyme was not established in the abstract; do not assign the activity to TXNRD1. exposure: Control and selenium-deficient rat liver microsome assays cross_nutrient: true [may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039

evidence_span

{"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"}

experimental_model

Radiotracer conversion and cytosolic enzyme assays

exposure

Diabetic rat versus controls; reduced pyridine-nucleotide cofactors

limitations

The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Goto-Kakizaki and Wistar rats

plain_language

Reduced niacin-derived cofactors supported the observed conversion.

primary_references

[ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3

tissue_or_cell_type

Liver, muscle, kidney and adipose preparations

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1185–1196

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer conversion and cytosolic enzyme assays · source_derived_draft · unverified_draft

### ino-epimerase-nadh The rat cytosolic epimerase assay required NADH and NADPH for full activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced niacin-derived cofactors supported the observed conversion. organism: Goto-Kakizaki and Wistar rats tissue_or_cell_type: Liver, muscle, kidney and adipose preparations experimental_model: Radiotracer conversion and cytosolic enzyme assays limitations: The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio. exposure: Diabetic rat versus controls; reduced pyridine-nucleotide cofactors evidence_span: {"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"} [ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3

evidence_access

Primary abstract

experimental_model

Cell-free NADH/NADPH oxidation experiments.

limitations

Not evidence of a measured whole-body NAD shortage.

nutrient_topic

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

plain_language

Reducing equivalents can be consumed by a metal-dependent reaction.

primary_references

Vanadate-mediated oxidation of NADH: description of an in vitro system requiring ascorbate and phosphate. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2735768/ · DOI 10.1016/0003-9861(89)90196-3

Vanadium: speciation, phosphate-sensitive enzymes 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 NADH/NADPH oxidation experiments. · source_derived_draft · unverified_draft

## vanadium-nadh-oxidation Reducing equivalents can be consumed by a metal-dependent reaction. A vanadate/ascorbate/phosphate system oxidized NADH, with similar results for NADPH, through a proposed superoxide-initiated chain reaction. Model: Cell-free NADH/NADPH oxidation experiments. Limitations: Not evidence of a measured whole-body NAD shortage. Evidence access: Primary abstract Vanadate-mediated oxidation of NADH: description of an in vitro system requiring ascorbate and phosphate. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2735768/ · DOI 10.1016/0003-9861(89)90196-3

evidence_span

{"source_cache": "artifacts/coq10-research/38425362.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d25af4ecd7340649536b8fea3b8a0a308a1611bbf8c57f6a79b362f443f1cba", "start_char": 23488, "end_char": 27391, "text_sha256": "7147c9d517477cd7bbec4a155e5f13bc733d294380975977eba11b64517047f3"}

experimental_model

Purified reconstructed COQ metabolon with short-chain substrates

exposure

Enzyme combinations, methyl donors, reductants and metal additions

limitations

Ancestral proteins and CoQ1 analogues; no clinical cofactor dose or proof of nutritional rate limitation. Reaction order need not be universal across species.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Reconstructed ancestral tetrapod proteins

plain_language

Niacin-derived reducing power also feeds a later synthesis step.

primary_references

[coq10-p38425362] In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. (2024). https://pubmed.ncbi.nlm.nih.gov/38425362/ DOI: 10.1038/s41929-023-01087-z

tissue_or_cell_type

Stepwise CoQ head-group assembly

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 723–734

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified reconstructed COQ metabolon with short-chain substrates · source_derived_draft · unverified_draft

### coq10-coq7-nadh COQ7 hydroxylation assays consumed NADH in a substrate-dependent manner. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Niacin-derived reducing power also feeds a later synthesis step. organism: Reconstructed ancestral tetrapod proteins tissue_or_cell_type: Stepwise CoQ head-group assembly experimental_model: Purified reconstructed COQ metabolon with short-chain substrates limitations: Ancestral proteins and CoQ1 analogues; no clinical cofactor dose or proof of nutritional rate limitation. Reaction order need not be universal across species. exposure: Enzyme combinations, methyl donors, reductants and metal additions evidence_span: {"source_cache": "artifacts/coq10-research/38425362.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d25af4ecd7340649536b8fea3b8a0a308a1611bbf8c57f6a79b362f443f1cba", "start_char": 23488, "end_char": 27391, "text_sha256": "7147c9d517477cd7bbec4a155e5f13bc733d294380975977eba11b64517047f3"} [coq10-p38425362] In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. (2024). https://pubmed.ncbi.nlm.nih.gov/38425362/ DOI: 10.1038/s41929-023-01087-z

evidence_access

Primary abstract

experimental_model

Human QDPR expressed in E. coli; enzyme purification, kinetic characterization and structure.

limitations

This binary structure alone does not show that niacin supplementation changes phenylalanine clearance.

nutrient_topic

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

plain_language

The cofactor-recycling network includes an NADH-binding enzyme.

primary_references

The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8262916/

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 70–76

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human QDPR expressed in E. coli; enzyme purification, kinetic characterization and structure. · source_derived_draft · unverified_draft

## l-phenylalanine-qdpr-nadh The cofactor-recycling network includes an NADH-binding enzyme. A catalytically characterized recombinant human dihydropteridine reductase was crystallized in complex with NADH at 2.5-angstrom resolution. Model: Human QDPR expressed in E. coli; enzyme purification, kinetic characterization and structure. Limitations: This binary structure alone does not show that niacin supplementation changes phenylalanine clearance. Evidence access: Primary abstract The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8262916/

evidence_access

Primary full text

experimental_model

Human cancer-cell hypoxia experiments and three-dimensional/xenograft models.

limitations

A benefit to tumor-cell survival is not a health benefit of supplementation; proline production is part of the reaction that consumes NADH.

nutrient_topic

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

plain_language

Making proline can also help rebalance mitochondrial reducing power.

primary_references

Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 350–356

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell hypoxia experiments and three-dimensional/xenograft models. · source_derived_draft · unverified_draft

## l-proline-pycr1-hypoxic-redox Making proline can also help rebalance mitochondrial reducing power. In hypoxic cancer models, increased PYCR1-dependent proline synthesis oxidized NADH and helped sustain TCA-cycle activity. Model: Human cancer-cell hypoxia experiments and three-dimensional/xenograft models. Limitations: A benefit to tumor-cell survival is not a health benefit of supplementation; proline production is part of the reaction that consumes NADH. Evidence access: Primary full text Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320

experimental_model

Cell-free LPO/H2O2 reactions with nicotinamide nucleotides.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Oxidized iodine can carry the reaction onward.

primary_references

The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 272–278

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. · source_derived_draft · unverified_draft

## ki-iodine-nadh Oxidized iodine can carry the reaction onward. Molecular iodine oxidized NADH without enzyme and was proposed as an intermediate of iodide-dependent oxidation. Model: Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. Limitations: Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva. Evidence location: Primary abstract The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

experimental_model

Cell-free LPO/H2O2 reactions with nicotinamide nucleotides.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

The NADH reaction did not simply regenerate normal NAD+.

primary_references

The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 256–262

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. · source_derived_draft · unverified_draft

## ki-nadh The NADH reaction did not simply regenerate normal NAD+. LPO/H2O2/iodide oxidized NADH to a product chemically distinct from NAD+, unlike the thiocyanate and bromide systems. Model: Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. Limitations: Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva. Evidence location: Primary abstract The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 9582, "end_char": 11594, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "ffd25dd072f6f8f486b11ca632f28acf37e3ef2b0dbd2b20eecf32fce649eaf1"}

experimental_model

Purified NADK2 Δ62

exposure

ATP-dependent NADH versus NAD+ assays

limitations

Relative activity under the reported substrate conditions; not a universal cellular flux ratio.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

NADK2 could phosphorylate NADH in this assay, but favored NAD+.

primary_references

[nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

tissue_or_cell_type

Purified enzyme

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 899–910

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified NADK2 Δ62 · source_derived_draft · unverified_draft

### b3-redox-nadk2-nadh-preference The tested NADH kinase activity of purified human NADK2 Δ62 was about 10% of its NAD+ kinase activity. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NADK2 could phosphorylate NADH in this assay, but favored NAD+. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Purified NADK2 Δ62 limitations: Relative activity under the reported substrate conditions; not a universal cellular flux ratio. exposure: ATP-dependent NADH versus NAD+ assays evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 9582, "end_char": 11594, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "ffd25dd072f6f8f486b11ca632f28acf37e3ef2b0dbd2b20eecf32fce649eaf1"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

evidence_access

Primary abstract

experimental_model

Established biochemical function in a primary loss-of-function/rescue study.

limitations

The protein also has essential functions beyond this reaction; metabolic activity alone does not explain its disease phenotype.

nutrient_topic

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

plain_language

Another enzyme changes the intermediate before the final carbon split.

primary_references

A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20077426/ · DOI 10.1002/emmm.200900055

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 210–216

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established biochemical function in a primary loss-of-function/rescue study. · source_derived_draft · unverified_draft

## isoleucine-hsd10-reaction Another enzyme changes the intermediate before the final carbon split. HSD17B10 encodes the 2-methyl-3-hydroxybutyryl-CoA dehydrogenase step of isoleucine metabolism. Model: Established biochemical function in a primary loss-of-function/rescue study. Limitations: The protein also has essential functions beyond this reaction; metabolic activity alone does not explain its disease phenotype. Evidence access: Primary abstract A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20077426/ · DOI 10.1002/emmm.200900055

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Germ-free mouse colonocytes and ex-vivo substrate addition.

limitations

Germ-free status removes many microbial functions; rescue supports a butyrate contribution without making every change a specific deficiency effect.

nutrient_topic

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

plain_language

Removing the microbiota deprived colon cells of an important fuel; adding it back restored respiration.

primary_references

The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21531334/ · DOI 10.1016/j.cmet.2011.02.018

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 166–172

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Germ-free mouse colonocytes and ex-vivo substrate addition. · source_derived_draft · unverified_draft

## butyrate-germfree-energy Removing the microbiota deprived colon cells of an important fuel; adding it back restored respiration. Germ-free mouse colonocytes had reduced NADH/NAD+, oxidative phosphorylation and ATP; adding butyrate rescued mitochondrial respiration. Model: Germ-free mouse colonocytes and ex-vivo substrate addition. Limitations: Germ-free status removes many microbial functions; rescue supports a butyrate contribution without making every change a specific deficiency effect. Evidence access: Primary abstract The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21531334/ · DOI 10.1016/j.cmet.2011.02.018

evidence_access

Primary abstract

experimental_model

Recombinant human FMO1 biochemistry.

limitations

NAD(P)H availability, FMO1 abundance and substrate availability are separate variables; no niacin repletion effect was tested.

nutrient_topic

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

plain_language

Niacin-derived electron carriers support this synthetic reaction.

primary_references

Flavin-Containing Monooxygenase 1 Catalyzes the Production of Taurine from Hypotaurine. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32156684/ · DOI 10.1124/dmd.119.089995

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 81–87

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human FMO1 biochemistry. · source_derived_draft · unverified_draft

## taurine-fmo1-reducing-cofactors Niacin-derived electron carriers support this synthetic reaction. Human FMO1 converted hypotaurine to taurine with either NADPH or NADH as the reducing cofactor in the reported assays. Model: Recombinant human FMO1 biochemistry. Limitations: NAD(P)H availability, FMO1 abundance and substrate availability are separate variables; no niacin repletion effect was tested. Evidence access: Primary abstract Flavin-Containing Monooxygenase 1 Catalyzes the Production of Taurine from Hypotaurine. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32156684/ · DOI 10.1124/dmd.119.089995

evidence_access

Primary abstract

experimental_model

Cell-free concentration-response experiments.

limitations

Not an established supplement dose-response in humans.

nutrient_topic

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

plain_language

The direction of an antioxidant’s effect can depend on concentration.

primary_references

Vanadate-mediated oxidation of NADH: description of an in vitro system requiring ascorbate and phosphate. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2735768/ · DOI 10.1016/0003-9861(89)90196-3

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 134–140

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free concentration-response experiments. · source_derived_draft · unverified_draft

## vanadium-ascorbate-concentration The direction of an antioxidant’s effect can depend on concentration. Ascorbate initiated NADH oxidation at lower concentrations but inhibited it at higher concentrations in the same chemical system. Model: Cell-free concentration-response experiments. Limitations: Not an established supplement dose-response in humans. Evidence access: Primary abstract Vanadate-mediated oxidation of NADH: description of an in vitro system requiring ascorbate and phosphate. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2735768/ · DOI 10.1016/0003-9861(89)90196-3

evidence_access

Primary full text

experimental_model

Ammonium metavanadate diets reported as 30 or 45 mg V/kg feed; 42-day duck study.

limitations

Observational pathway measurements after exposure, not direct enzyme inhibition or a human ferroptosis mechanism. Methods inconsistently say three and four groups while listing control plus two exposure groups.

nutrient_topic

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

plain_language

An animal toxicity study links the exposure to a lipid-defense pathway.

primary_references

Dual-pathway mechanism of vanadium-induced hepatotoxicity in ducks: Synergistic crosstalk between glucose homeostasis disruption and NADH/FSP1/COQ10 axis-driven ferroptosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41362732/ · DOI 10.7150/ijbs.123482

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 358–364

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ammonium metavanadate diets reported as 30 or 45 mg V/kg feed; 42-day duck study. · source_derived_draft · unverified_draft

## vanadium-duck-redox-axis An animal toxicity study links the exposure to a lipid-defense pathway. Dietary vanadium overexposure in ducks was associated with lower NADH/FSP1/CoQ10-axis measures and increased hepatic lipid peroxidation and Fe2+ accumulation. Model: Ammonium metavanadate diets reported as 30 or 45 mg V/kg feed; 42-day duck study. Limitations: Observational pathway measurements after exposure, not direct enzyme inhibition or a human ferroptosis mechanism. Methods inconsistently say three and four groups while listing control plus two exposure groups. Evidence access: Primary full text Dual-pathway mechanism of vanadium-induced hepatotoxicity in ducks: Synergistic crosstalk between glucose homeostasis disruption and NADH/FSP1/COQ10 axis-driven ferroptosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41362732/ · DOI 10.7150/ijbs.123482

evidence_access

Primary abstract

experimental_model

Isolated fish cardiac mitochondrial assays.

limitations

Complex-III redox change does not itself establish a direct molecular binding target.

nutrient_topic

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

plain_language

Respiratory inhibition did not mean every mitochondrial enzyme was inhibited.

primary_references

Mitochondria as a target for decavanadate toxicity in Sparus aurata heart. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17420061/ · DOI 10.1016/j.aquatox.2007.03.005

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 318–324

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated fish cardiac mitochondrial assays. · source_derived_draft · unverified_draft

## vanadium-fish-target-specificity Respiratory inhibition did not mean every mitochondrial enzyme was inhibited. Up to 5 micromolar V10 did not inhibit measured F0F1-ATPase activity, NADH levels or complexes I/II, while complex-III redox steady state changed. Model: Isolated fish cardiac mitochondrial assays. Limitations: Complex-III redox change does not itself establish a direct molecular binding target. Evidence access: Primary abstract Mitochondria as a target for decavanadate toxicity in Sparus aurata heart. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17420061/ · DOI 10.1016/j.aquatox.2007.03.005

evidence_access

Primary abstract

experimental_model

Cell-free scavenger comparison.

limitations

Does not imply catalase is irrelevant to all vanadium toxicity.

nutrient_topic

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

plain_language

The scavenger comparison points to a superoxide-dependent step in this particular reaction.

primary_references

Vanadate-mediated oxidation of NADH: description of an in vitro system requiring ascorbate and phosphate. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2735768/ · DOI 10.1016/0003-9861(89)90196-3

Vanadium: speciation, phosphate-sensitive enzymes 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 · Cell-free scavenger comparison. · source_derived_draft · unverified_draft

## vanadium-sod-redox-rescue The scavenger comparison points to a superoxide-dependent step in this particular reaction. Superoxide dismutase inhibited NADH oxidation in the vanadate/ascorbate/phosphate system, whereas catalase and ethanol did not. Model: Cell-free scavenger comparison. Limitations: Does not imply catalase is irrelevant to all vanadium toxicity. Evidence access: Primary abstract Vanadate-mediated oxidation of NADH: description of an in vitro system requiring ascorbate and phosphate. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2735768/ · DOI 10.1016/0003-9861(89)90196-3

evidence_span

{"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"}

experimental_model

Proteoliposome enzyme kinetics

exposure

Ubiquinones with one to ten isoprenoid units

limitations

Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Mammalian complex I preparation

plain_language

CoQ receives electrons from the first respiratory complex.

primary_references

[coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114

tissue_or_cell_type

Membrane quinone channel

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 385–396

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

### coq10-complex-i-q Complex I transferred electrons from NADH to ubiquinone-10 in reconstituted membranes. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ receives electrons from the first respiratory complex. organism: Mammalian complex I preparation tissue_or_cell_type: Membrane quinone channel experimental_model: Proteoliposome enzyme kinetics limitations: Purified enzyme system; short-chain analogues do not have identical binding and release kinetics to Q10. exposure: Ubiquinones with one to ten isoprenoid units evidence_span: {"source_cache": "artifacts/coq10-research/29133414.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d", "start_char": 0, "end_char": 1770, "text_sha256": "139122e8a567596e6ec1b4bd361567d0e5cd4e3329fec72d47b949a86d29610d"} [coq10-p29133414] Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. (2017). https://pubmed.ncbi.nlm.nih.gov/29133414/ DOI: 10.1073/pnas.1714074114

evidence_span

{"source_cache": "artifacts/coq10-research/31634899.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe", "start_char": 0, "end_char": 1818, "text_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe"}

experimental_model

Expression cloning and cell-death experiments

exposure

GPX4 deletion or inhibitors and FSP1 manipulation

limitations

Cancer-cell defense mechanism; preventing ferroptosis is not always a desirable disease outcome and oral CoQ benefit is not tested.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Human cancer-cell models

plain_language

The antioxidant form must be regenerated using reducing power.

primary_references

[coq10-p31634899] FSP1 is a glutathione-independent ferroptosis suppressor. (2019). https://pubmed.ncbi.nlm.nih.gov/31634899/ DOI: 10.1038/s41586-019-1707-0

tissue_or_cell_type

FSP1-CoQ antioxidant pathway

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 801–812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression cloning and cell-death experiments · source_derived_draft · unverified_draft

### coq10-fsp1-nadph FSP1 used NAD(P)H to regenerate the reduced CoQ pool that traps lipid peroxyl radicals. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant form must be regenerated using reducing power. organism: Human cancer-cell models tissue_or_cell_type: FSP1-CoQ antioxidant pathway experimental_model: Expression cloning and cell-death experiments limitations: Cancer-cell defense mechanism; preventing ferroptosis is not always a desirable disease outcome and oral CoQ benefit is not tested. exposure: GPX4 deletion or inhibitors and FSP1 manipulation evidence_span: {"source_cache": "artifacts/coq10-research/31634899.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe", "start_char": 0, "end_char": 1818, "text_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe"} [coq10-p31634899] FSP1 is a glutathione-independent ferroptosis suppressor. (2019). https://pubmed.ncbi.nlm.nih.gov/31634899/ DOI: 10.1038/s41586-019-1707-0

evidence_span

{"source_cache": "artifacts/coq10-research/12435734.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "929e8de2bc15ea62eb4a3814995fd289de759d721f16b848174ad65f95847c55", "start_char": 0, "end_char": 1340, "text_sha256": "929e8de2bc15ea62eb4a3814995fd289de759d721f16b848174ad65f95847c55"}

experimental_model

Enzyme kinetics, mutants and overexpressing-cell homogenates

exposure

NADPH or NADH; selenite and selenium-deprived enzyme variants

limitations

Biochemical selenium dependence; not proof that all CoQ recycling stops with low selenium or that combined supplements are synergistic clinically.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Mammalian TrxR1 and human HEK293 cells

plain_language

A selenium-dependent enzyme can regenerate the antioxidant form of CoQ.

primary_references

[coq10-p12435734] The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/12435734/ DOI: 10.1074/jbc.m210456200

tissue_or_cell_type

Ubiquinone reduction

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 762–773

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme kinetics, mutants and overexpressing-cell homogenates · source_derived_draft · unverified_draft

### coq10-txnrd1-coq Mammalian TrxR1 reduced ubiquinone-10 to ubiquinol-10. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A selenium-dependent enzyme can regenerate the antioxidant form of CoQ. organism: Mammalian TrxR1 and human HEK293 cells tissue_or_cell_type: Ubiquinone reduction experimental_model: Enzyme kinetics, mutants and overexpressing-cell homogenates limitations: Biochemical selenium dependence; not proof that all CoQ recycling stops with low selenium or that combined supplements are synergistic clinically. exposure: NADPH or NADH; selenite and selenium-deprived enzyme variants evidence_span: {"source_cache": "artifacts/coq10-research/12435734.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "929e8de2bc15ea62eb4a3814995fd289de759d721f16b848174ad65f95847c55", "start_char": 0, "end_char": 1340, "text_sha256": "929e8de2bc15ea62eb4a3814995fd289de759d721f16b848174ad65f95847c55"} [coq10-p12435734] The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/12435734/ DOI: 10.1074/jbc.m210456200

cross_nutrient

B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.

evidence

[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human DLD crystallography with NAD+ and NADH.

limitations

Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.

primary_references

[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014

tissue_or_cell_type

Purified enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft

### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014

cross_nutrient

B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.

evidence

[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Reconstituted human multienzyme assay.

limitations

NADH assay measures overall complex turnover, not every intermediate independently.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.

primary_references

[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

tissue_or_cell_type

Purified enzyme complex

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867

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

### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

evidence_span

{"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"}

experimental_model

Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice

exposure

MK-4/K1, NAD(P)H, FSP1 loss and inhibitors

limitations

Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human recombinant FSP1, mammalian cells and mice

plain_language

A niacin-derived electron donor helps regenerate the reduced antioxidant form.

primary_references

[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

tissue_or_cell_type

Lipid peroxidation and vitamin K reduction

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 773–784

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft

### k2-fsp1-k-reduction FSP1 reduced vitamin K quinones to radical-trapping hydroquinones using NAD(P)H. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A niacin-derived electron donor helps regenerate the reduced antioxidant form. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}]

experimental_model

Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.

exposure

10 micromolar FMN after NADH/respiratory blockade at pH 10.

limitations

pH 10 treatment; not a test of dietary deficiency or oral supplementation.

nutrient_topic

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

organism

Bos taurus

plain_language

Putting the correct flavin back restored this experimentally inactivated respiratory enzyme.

primary_references

[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

tissue_or_cell_type

Heart submitochondrial particles

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 570–581

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft

### b2-met-complex-i-fmn-reconstitution FMN restored rotenone-sensitive NADH:quinone reductase activity after alkaline reductive inactivation of bovine membrane-bound complex I. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Putting the correct flavin back restored this experimentally inactivated respiratory enzyme. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: pH 10 treatment; not a test of dietary deficiency or oral supplementation. exposure: 10 micromolar FMN after NADH/respiratory blockade at pH 10. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 19, "char_start": 0, "char_end": 1242, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Neonatal rat ventricular myocyte knockdown assays.

limitations

These are related cellular readouts, not proof of human niacin or phenylalanine deficiency.

nutrient_topic

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

plain_language

The downstream effects include both energy production and redox balance.

primary_references

FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38362779/ · DOI 10.1161/CIRCULATIONAHA.123.064489

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 158–164

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neonatal rat ventricular myocyte knockdown assays. · source_derived_draft · unverified_draft

## l-phenylalanine-mitochondrial-energy The downstream effects include both energy production and redox balance. Fars2 knockdown in neonatal rat ventricular myocytes lowered ATP and mitochondrial membrane potential, increased ROS, and reduced the NAD+/NADH ratio. Model: Neonatal rat ventricular myocyte knockdown assays. Limitations: These are related cellular readouts, not proof of human niacin or phenylalanine deficiency. Evidence access: Primary full text FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38362779/ · DOI 10.1161/CIRCULATIONAHA.123.064489

evidence_access

Primary full text

experimental_model

Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate.

limitations

NADHX is chemically damaged NADH, not simply a low NAD+ concentration.

nutrient_topic

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

plain_language

Repair of a niacin-derived cofactor protects a separate amino-acid pathway.

primary_references

Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

L-Serine: synthesis, one-carbon metabolism, lipids 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 · Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate. · source_derived_draft · unverified_draft

## l-serine-nadhx-inhibition Repair of a niacin-derived cofactor protects a separate amino-acid pathway. Purified NADHX species inhibited recombinant human PHGDH, supporting direct inhibition as an explanation for the serine-synthesis defect in NAXD-deficient cells. Model: Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate. Limitations: NADHX is chemically damaged NADH, not simply a low NAD+ concentration. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human knockout cells, patient fibroblasts and isotope tracing.

limitations

The impairment depended on culture conditions and was more pronounced under galactose stress.

nutrient_topic

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

plain_language

Damaged cofactor can block a pathway even when the enzyme is still present.

primary_references

Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids 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 · Human knockout cells, patient fibroblasts and isotope tracing. · source_derived_draft · unverified_draft

## l-serine-naxd-block Damaged cofactor can block a pathway even when the enzyme is still present. NAXD loss caused NADHX accumulation and impaired de novo serine synthesis in human HAP1 cells under galactose stress and in patient-derived fibroblasts. Model: Human knockout cells, patient fibroblasts and isotope tracing. Limitations: The impairment depended on culture conditions and was more pronounced under galactose stress. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

evidence_access

Primary abstract

experimental_model

Recombinant human PHGDH catalytic-domain structure and enzyme assays.

limitations

The truncated dimeric structure does not define the complete native oligomer.

nutrient_topic

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

plain_language

A glycolysis intermediate can be diverted into serine production.

primary_references

Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). · 2017 · https://pubmed.ncbi.nlm.nih.gov/29262655/ · DOI 10.18632/oncotarget.22327

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 14–20

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

## l-serine-phgdh-reaction A glycolysis intermediate can be diverted into serine production. Human PHGDH catalyzes the NAD+-dependent oxidation of 3-phosphoglycerate to phosphohydroxypyruvate, the first step of phosphorylated serine biosynthesis. Model: Recombinant human PHGDH catalytic-domain structure and enzyme assays. Limitations: The truncated dimeric structure does not define the complete native oligomer. Evidence access: Primary abstract Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). · 2017 · https://pubmed.ncbi.nlm.nih.gov/29262655/ · DOI 10.18632/oncotarget.22327

evidence_access

Primary abstract

experimental_model

Human enzyme structures and kinetics; mouse enzyme complexes supplied high-resolution ligand views.

limitations

P5C and glutamate semialdehyde interconvert; the aldehyde is the oxidation substrate. Mouse ligand structures are not relabeled as human complexes.

nutrient_topic

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

plain_language

A second enzyme turns the breakdown intermediate into glutamate.

primary_references

The three-dimensional structural basis of type II hyperprolinemia. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22516612/ · DOI 10.1016/j.jmb.2012.04.010

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 102–108

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structures and kinetics; mouse enzyme complexes supplied high-resolution ligand views. · source_derived_draft · unverified_draft

## l-proline-aldh4-oxidation A second enzyme turns the breakdown intermediate into glutamate. ALDH4A1 catalyzes NAD+-dependent oxidation of glutamate semialdehyde to glutamate, completing the second enzymatic stage of proline catabolism. Model: Human enzyme structures and kinetics; mouse enzyme complexes supplied high-resolution ligand views. Limitations: P5C and glutamate semialdehyde interconvert; the aldehyde is the oxidation substrate. Mouse ligand structures are not relabeled as human complexes. Evidence access: Primary abstract The three-dimensional structural basis of type II hyperprolinemia. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22516612/ · DOI 10.1016/j.jmb.2012.04.010

evidence_access

Primary full text

experimental_model

Purified human enzyme; comparison with 0.1 mM P5C and 0.1 mM reduced cofactor, 37 degrees C.

limitations

Cofactor preference depends on assay conditions and does not make the alternative cofactor unusable.

nutrient_topic

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

plain_language

One mitochondrial enzyme finishes the synthesis of proline.

primary_references

Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 14–20

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; comparison with 0.1 mM P5C and 0.1 mM reduced cofactor, 37 degrees C. · source_derived_draft · unverified_draft

## l-proline-pycr1-reduction One mitochondrial enzyme finishes the synthesis of proline. Recombinant human PYCR1 reduced P5C to proline with NADH or NADPH; in the tested conditions its specific activity was higher with NADH. Model: Purified human enzyme; comparison with 0.1 mM P5C and 0.1 mM reduced cofactor, 37 degrees C. Limitations: Cofactor preference depends on assay conditions and does not make the alternative cofactor unusable. Evidence access: Primary full text Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

evidence_access

Primary full text

experimental_model

Purified human PYCR2 and human melanoma-cell localization experiments.

limitations

PYCR2 has its own identity and disease associations; it is not interchangeable with PYCR1.

nutrient_topic

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

plain_language

A second mitochondrial enzyme performs the final reduction.

primary_references

Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 22–28

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human PYCR2 and human melanoma-cell localization experiments. · source_derived_draft · unverified_draft

## l-proline-pycr2-reduction A second mitochondrial enzyme performs the final reduction. Recombinant human PYCR2 reduced P5C to proline and favored NADH over NADPH under the reported comparison conditions. Model: Purified human PYCR2 and human melanoma-cell localization experiments. Limitations: PYCR2 has its own identity and disease associations; it is not interchangeable with PYCR1. Evidence access: Primary full text Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

evidence_access

Primary abstract

experimental_model

Acinetobacter enzyme redox spectroscopy and site-directed mutants.

limitations

Bacterial cofactor dependence does not show that human B2 or iron supplementation increases TMAO.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

Riboflavin-derived FMN, iron centers and NADH connect to microbial carnitine chemistry.

primary_references

Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 394–400

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Acinetobacter enzyme redox spectroscopy and site-directed mutants. · source_derived_draft · unverified_draft

## l-carnitine-cntb-redox Riboflavin-derived FMN, iron centers and NADH connect to microbial carnitine chemistry. CntB passed NADH-derived electrons through FMN and iron-sulfur centers to support CntA oxygen activation. Model: Acinetobacter enzyme redox spectroscopy and site-directed mutants. Limitations: Bacterial cofactor dependence does not show that human B2 or iron supplementation increases TMAO. Evidence access: Primary abstract Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266

evidence_span

{"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"}

experimental_model

Cell respiration, isolated mitochondria and kinase perturbation

exposure

Berberine concentration-response; kinase deletion/inhibition

limitations

Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy.

nutrient_topic

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

organism

Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells

plain_language

Slowing one respiratory-chain step can trigger a cellular energy response.

primary_references

[berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552

tissue_or_cell_type

Respiratory complex I and AMPK

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 324–335

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell respiration, isolated mitochondria and kinase perturbation · source_derived_draft · unverified_draft

### berberine-complex-i Berberine inhibited respiration in L6 myotubes and muscle mitochondria through a complex-I-associated effect. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Slowing one respiratory-chain step can trigger a cellular energy response. organism: Rat L6 myotubes, muscle mitochondria and LKB1-deficient cells tissue_or_cell_type: Respiratory complex I and AMPK experimental_model: Cell respiration, isolated mitochondria and kinase perturbation limitations: Functional respiratory inhibition does not by itself establish direct binding to complex I or improved mitochondrial health. Preclinical exposure, not human efficacy. exposure: Berberine concentration-response; kinase deletion/inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18285556.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257", "start_char": 0, "end_char": 1735, "text_sha256": "cd721d78117d554be4fdb0403ac792f6723cf59cfd3679106607e8f17eafc257"} [berberine-p18285556] Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (2008). https://pubmed.ncbi.nlm.nih.gov/18285556/ DOI: 10.2337/db07-1552

evidence_access

Primary abstract

experimental_model

Rat liver and mitochondrial experiments.

limitations

The ketone ratio is a redox proxy, not a direct measurement of all NAD pools.

nutrient_topic

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

plain_language

The metabolic redox state shifted toward oxidation.

primary_references

Prooxidant activity of fisetin: effects on energy metabolism in the rat liver. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20957679/ · DOI 10.1002/jbt.20367

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 344–350

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver and mitochondrial experiments. · source_derived_draft · unverified_draft

## fisetin-rat-redox-ketones The metabolic redox state shifted toward oxidation. In perfused fasted-rat liver, fisetin reduced ketogenesis and the beta-hydroxybutyrate/acetoacetate ratio. Model: Rat liver and mitochondrial experiments. Limitations: The ketone ratio is a redox proxy, not a direct measurement of all NAD pools. Evidence access: Primary abstract Prooxidant activity of fisetin: effects on energy metabolism in the rat liver. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20957679/ · DOI 10.1002/jbt.20367

dose

Tartrazine among tested substrates; exact substrate/cofactor concentrations unavailable in abstract

duration

Assay interval unavailable in primary abstract

evidence_access

Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Purified Escherichia coli K12 azoreductases I and II

limitations

Both NADH and NADPH served as electron donors in enzyme characterization. This does not prove that niacin intake controls dye metabolism in humans. Protein genes and tartrazine-specific kinetic constants are unresolved.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Purified Escherichia coli K12 azoreductases I and II

plain_language

Purified E. coli K12 azoreductase I used tartrazine as a substrate.

primary_references

Purification of two azoreductases from Escherichia coli K12. (1993). https://pubmed.ncbi.nlm.nih.gov/8112774/

route

In vitro enzyme/substrate incubation

tissue

Cell-free azo-reduction assays

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 17–26

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Purified Escherichia coli K12 azoreductases I and II · source_derived_draft · unverified_draft

## tartrazine-azoreductase-i Purified E. coli K12 azoreductase I used tartrazine as a substrate. Model/species: Purified Escherichia coli K12 azoreductases I and II Tissue: Cell-free azo-reduction assays Exposure: Tartrazine among tested substrates; exact substrate/cofactor concentrations unavailable in abstract Route: In vitro enzyme/substrate incubation Duration: Assay interval unavailable in primary abstract Limits: Both NADH and NADPH served as electron donors in enzyme characterization. This does not prove that niacin intake controls dye metabolism in humans. Protein genes and tartrazine-specific kinetic constants are unresolved. Primary reference: Purification of two azoreductases from Escherichia coli K12. (1993). https://pubmed.ncbi.nlm.nih.gov/8112774/ Access: Primary PubMed abstract; unrecovered method details explicitly retained.

dose

Tartrazine among tested substrates; exact substrate/cofactor concentrations unavailable in abstract

duration

Assay interval unavailable in primary abstract

evidence_access

Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Purified Escherichia coli K12 azoreductases I and II

limitations

Both NADH and NADPH served as electron donors in enzyme characterization. This does not prove that niacin intake controls dye metabolism in humans. Protein genes and tartrazine-specific kinetic constants are unresolved.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Purified Escherichia coli K12 azoreductases I and II

plain_language

Purified E. coli K12 azoreductase II used tartrazine less efficiently than azoreductase I.

primary_references

Purification of two azoreductases from Escherichia coli K12. (1993). https://pubmed.ncbi.nlm.nih.gov/8112774/

route

In vitro enzyme/substrate incubation

tissue

Cell-free azo-reduction assays

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 28–37

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Purified Escherichia coli K12 azoreductases I and II · source_derived_draft · unverified_draft

## tartrazine-azoreductase-ii Purified E. coli K12 azoreductase II used tartrazine less efficiently than azoreductase I. Model/species: Purified Escherichia coli K12 azoreductases I and II Tissue: Cell-free azo-reduction assays Exposure: Tartrazine among tested substrates; exact substrate/cofactor concentrations unavailable in abstract Route: In vitro enzyme/substrate incubation Duration: Assay interval unavailable in primary abstract Limits: Both NADH and NADPH served as electron donors in enzyme characterization. This does not prove that niacin intake controls dye metabolism in humans. Protein genes and tartrazine-specific kinetic constants are unresolved. Primary reference: Purification of two azoreductases from Escherichia coli K12. (1993). https://pubmed.ncbi.nlm.nih.gov/8112774/ Access: Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_span

{"source_cache": "artifacts/boron-research/11420139.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0792ce09223d7cf23f0d3fda6b793e6e3b9904abe2c1f934b96d50e3a0e8b703", "start_char": 0, "end_char": 1650, "text_sha256": "0792ce09223d7cf23f0d3fda6b793e6e3b9904abe2c1f934b96d50e3a0e8b703"}

experimental_model

Capillary electrophoresis of purified metabolites

exposure

Boron complexation under the reported assay conditions

limitations

Chemical affinity is not a demonstrated metabolic function or in-vivo occupancy. Rankings depend on assay and solution conditions.

nutrient_topic

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

organism

Cell-free chemistry

plain_language

The arrangement of neighboring hydroxyl groups helps determine which nucleotide molecules can bind boron.

primary_references

[boron-p11420139] Diadenosine phosphates and S-adenosylmethionine: novel boron binding biomolecules detected by capillary electrophoresis. (2001). https://pubmed.ncbi.nlm.nih.gov/11420139/ DOI: 10.1016/s0304-4165(01)00130-1

tissue_or_cell_type

Aqueous assay; no tissue

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 105–116

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Capillary electrophoresis of purified metabolites · source_derived_draft · unverified_draft

### boron-cis-diol-binding Boron binding in the tested nucleotide series depended on suitable cis-diol groups, and NAD+ bound more strongly than NADH in the capillary-electrophoresis assay. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The arrangement of neighboring hydroxyl groups helps determine which nucleotide molecules can bind boron. organism: Cell-free chemistry tissue_or_cell_type: Aqueous assay; no tissue experimental_model: Capillary electrophoresis of purified metabolites limitations: Chemical affinity is not a demonstrated metabolic function or in-vivo occupancy. Rankings depend on assay and solution conditions. exposure: Boron complexation under the reported assay conditions evidence_span: {"source_cache": "artifacts/boron-research/11420139.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0792ce09223d7cf23f0d3fda6b793e6e3b9904abe2c1f934b96d50e3a0e8b703", "start_char": 0, "end_char": 1650, "text_sha256": "0792ce09223d7cf23f0d3fda6b793e6e3b9904abe2c1f934b96d50e3a0e8b703"} [boron-p11420139] Diadenosine phosphates and S-adenosylmethionine: novel boron binding biomolecules detected by capillary electrophoresis. (2001). https://pubmed.ncbi.nlm.nih.gov/11420139/ DOI: 10.1016/s0304-4165(01)00130-1

evidence_span

{"source_cache": "artifacts/boron-research/15282753.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9385dca91d3dc7bb5a3d2a9c71a8e4c4ec0af136a15de2ea9536365a048d8057", "start_char": 0, "end_char": 1378, "text_sha256": "9385dca91d3dc7bb5a3d2a9c71a8e4c4ec0af136a15de2ea9536365a048d8057"}

experimental_model

Electrospray mass spectrometry comparing nucleotide binding

exposure

100 µM nucleotide and 500 µM boric acid in WAT solvent at pH 10.3; separate pH 7.4 ammonium bicarbonate condition

limitations

Relative ion signals and assay-specific rankings cannot be treated as universal binding constants or in-vivo metabolic effects.

nutrient_topic

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

organism

Cell-free chemistry

plain_language

Added phosphate groups and the test solution change the observed binding pattern.

primary_references

[boron-p15282753] Borate-nucleotide complex formation depends on charge and phosphorylation state. (2004). https://pubmed.ncbi.nlm.nih.gov/15282753/ DOI: 10.1002/jms.645

tissue_or_cell_type

Purified nucleotide solutions

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 144–155

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrospray mass spectrometry comparing nucleotide binding · source_derived_draft · unverified_draft

### boron-nad-phosphate-context The reported boron-binding order was NAD+ > NADH > NADP+ > NADPH at pH 10.3; only the NAD+ complex was observed in the separate pH 7.4 ammonium-bicarbonate condition. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Added phosphate groups and the test solution change the observed binding pattern. organism: Cell-free chemistry tissue_or_cell_type: Purified nucleotide solutions experimental_model: Electrospray mass spectrometry comparing nucleotide binding limitations: Relative ion signals and assay-specific rankings cannot be treated as universal binding constants or in-vivo metabolic effects. exposure: 100 µM nucleotide and 500 µM boric acid in WAT solvent at pH 10.3; separate pH 7.4 ammonium bicarbonate condition evidence_span: {"source_cache": "artifacts/boron-research/15282753.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9385dca91d3dc7bb5a3d2a9c71a8e4c4ec0af136a15de2ea9536365a048d8057", "start_char": 0, "end_char": 1378, "text_sha256": "9385dca91d3dc7bb5a3d2a9c71a8e4c4ec0af136a15de2ea9536365a048d8057"} [boron-p15282753] Borate-nucleotide complex formation depends on charge and phosphorylation state. (2004). https://pubmed.ncbi.nlm.nih.gov/15282753/ DOI: 10.1002/jms.645

evidence_span

{"source_cache": "artifacts/metformin-research/24847880.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8378baac19afd12fd3ca66206d079db20e7229a9295414e9678979352e10d92b", "start_char": 0, "end_char": 1499, "text_sha256": "8378baac19afd12fd3ca66206d079db20e7229a9295414e9678979352e10d92b"}

experimental_model

Rat antisense-oligonucleotide knockdown, whole-body knockout mice and hepatic redox measurements

exposure

Acute and chronic low-dose metformin; mGPD knockdown and knockout

limitations

A redox-shuttle mechanism established in rodents at low doses; it does not by itself exclude complex I or AMPK contributions in other tissues.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Rat and mouse

plain_language

Blocking the shuttle leaves reducing power stranded in the cell fluid.

primary_references

[metformin-p24847880] Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. (2014). https://pubmed.ncbi.nlm.nih.gov/24847880/ DOI: 10.1038/nature13270

tissue_or_cell_type

Liver

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 476–487

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat antisense-oligonucleotide knockdown, whole-body knockout mice and hepatic redox measurements · source_derived_draft · unverified_draft

### metformin-mgpd-redox Low-dose metformin increased the cytosolic redox state and decreased the mitochondrial redox state in the liver. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Blocking the shuttle leaves reducing power stranded in the cell fluid. organism: Rat and mouse tissue_or_cell_type: Liver experimental_model: Rat antisense-oligonucleotide knockdown, whole-body knockout mice and hepatic redox measurements limitations: A redox-shuttle mechanism established in rodents at low doses; it does not by itself exclude complex I or AMPK contributions in other tissues. exposure: Acute and chronic low-dose metformin; mGPD knockdown and knockout evidence_span: {"source_cache": "artifacts/metformin-research/24847880.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8378baac19afd12fd3ca66206d079db20e7229a9295414e9678979352e10d92b", "start_char": 0, "end_char": 1499, "text_sha256": "8378baac19afd12fd3ca66206d079db20e7229a9295414e9678979352e10d92b"} [metformin-p24847880] Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. (2014). https://pubmed.ncbi.nlm.nih.gov/24847880/ DOI: 10.1038/nature13270

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Cultured proliferating mammalian cells with impaired respiration.

limitations

ATP is not generally dispensable; this experiment isolates an electron-acceptor bottleneck in supplied culture conditions.

nutrient_topic

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

plain_language

Respiration supports building material by restoring electron acceptors, as well as producing ATP.

primary_references

Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017

trigger_kind

machinery_impairment Imported condition classification; unverified.

NAD+: compartmental supply, consumption 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 · Cultured proliferating mammalian cells with impaired respiration. · source_derived_draft · unverified_draft

## nad-plus-electron-acceptor-aspartate Respiration supports building material by restoring electron acceptors, as well as producing ATP. Respiration-deficient proliferating cells became limited in aspartate synthesis; alpha-ketobutyrate restored proliferation as an electron acceptor without supplying carbon or ATP. Model: Cultured proliferating mammalian cells with impaired respiration. Limitations: ATP is not generally dispensable; this experiment isolates an electron-acceptor bottleneck in supplied culture conditions. Evidence access: Primary full text Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell pharmacological inhibition and proliferation assay.

limitations

Inhibitor results do not resolve individual LDH isoforms or establish a clinical combination.

nutrient_topic

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

plain_language

Blocking the backup redox route removes its rescue effect.

primary_references

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

trigger_kind

machinery_impairment Imported condition classification; unverified.

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 356–362

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell pharmacological inhibition and proliferation assay. · source_derived_draft · unverified_draft

## nad-plus-ldh-inhibition Blocking the backup redox route removes its rescue effect. The LDH inhibitor GSK2837808A partially inhibited pyruvate-to-lactate conversion and restored metformin sensitivity in pyruvate-containing cancer-cell medium. Model: Human cancer-cell pharmacological inhibition and proliferation assay. Limitations: Inhibitor results do not resolve individual LDH isoforms or establish a clinical combination. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

evidence_access

Primary full text

experimental_model

Human cancer-cell nutrient manipulation and NAD+/NADH measurements.

limitations

Reaction-level LDH activity is recorded without assigning an untested isoform.

nutrient_topic

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

plain_language

An electron acceptor can restore NAD without making new NAD molecules.

primary_references

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 348–354

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell nutrient manipulation and NAD+/NADH measurements. · source_derived_draft · unverified_draft

## nad-plus-ldh-redox An electron acceptor can restore NAD without making new NAD molecules. In the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition. Model: Human cancer-cell nutrient manipulation and NAD+/NADH measurements. Limitations: Reaction-level LDH activity is recorded without assigning an untested isoform. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

evidence_access

Primary full text

experimental_model

Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation.

limitations

Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues.

nutrient_topic

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

plain_language

Available nutrients can change the effect of an inhibitor on the same pathway.

primary_references

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 220–226

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. · source_derived_draft · unverified_draft

## nad-plus-pyruvate-metformin Available nutrients can change the effect of an inhibitor on the same pathway. Pyruvate supplied an alternative electron-acceptor route for NAD+ regeneration and aspartate synthesis, reducing the antiproliferative effect of metformin in the tested cancer cells. Model: Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. Limitations: Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cultured-cell knockout, metabolomics and isolated-mitochondrial assays.

limitations

Cellular transporter disruption, not proof that oral NAD crosses all membranes or treats a transporter disorder.

nutrient_topic

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

plain_language

A functioning NAD supply outside mitochondria cannot compensate for a broken mitochondrial entry route.

primary_references

MCART1/SLC25A51 is required for mitochondrial NAD transport. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33087354/ · DOI 10.1126/sciadv.abe5310

trigger_kind

machinery_impairment Imported condition classification; unverified.

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 36–42

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured-cell knockout, metabolomics and isolated-mitochondrial assays. · source_derived_draft · unverified_draft

## nad-plus-slc51-respiration A functioning NAD supply outside mitochondria cannot compensate for a broken mitochondrial entry route. MCART1/SLC25A51-null human cells had reduced mitochondrial NAD+/NADH, TCA-cycle flux, respiration and complex-I activity. Model: Human cultured-cell knockout, metabolomics and isolated-mitochondrial assays. Limitations: Cellular transporter disruption, not proof that oral NAD crosses all membranes or treats a transporter disorder. Evidence access: Primary full text MCART1/SLC25A51 is required for mitochondrial NAD transport. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33087354/ · DOI 10.1126/sciadv.abe5310

evidence_access

Primary abstract

experimental_model

Mouse-cell isolated mitochondrial experiments.

limitations

The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep.

nutrient_topic

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

plain_language

The pathway has several gates, with different requirements at different steps.

primary_references

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 276–282

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-cell isolated mitochondrial experiments. · source_derived_draft · unverified_draft

## l-cysteine-nfs1-persulfide-gate The pathway has several gates, with different requirements at different steps. Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step. Model: Mouse-cell isolated mitochondrial experiments. Limitations: The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nnt-structure-2019.abstract.txt", "locator": "Indexed abstract, reaction and structural mechanism", "start_char": 199, "end_char": 1759, "file_sha256": "edb35c2cdf2f57d604cb86da48665e5742d398f43c50f3e1622d161564c78a83", "text_sha256": "aa5063e57c35097c2fa2557ed9a7d61c3a411d90d0ded9b947525012520a5712"}

experimental_model

Cryo-EM of intact ovine NNT in different nucleotide states

exposure

Nucleotide-bound conformational states

limitations

Structural mechanism supported in ovine protein; forward flux is context dependent and not equivalent to adding phosphate to NAD. No human intake inference.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Ovis aries

plain_language

NNT links the NADH and NADPH redox systems through membrane-coupled chemistry.

primary_references

[nnt-structure-2019] Structure and mechanism of mitochondrial proton-translocating transhydrogenase. (2019). https://pubmed.ncbi.nlm.nih.gov/31462775/ DOI: 10.1038/s41586-019-1519-2

tissue_or_cell_type

Purified mitochondrial protein

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1003–1014

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of intact ovine NNT in different nucleotide states · source_derived_draft · unverified_draft

### b3-redox-nnt-coupling Structural analysis of mammalian NNT supported coupling of NADH-to-NADP+ hydride transfer to proton translocation across the mitochondrial membrane. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NNT links the NADH and NADPH redox systems through membrane-coupled chemistry. organism: Ovis aries tissue_or_cell_type: Purified mitochondrial protein experimental_model: Cryo-EM of intact ovine NNT in different nucleotide states limitations: Structural mechanism supported in ovine protein; forward flux is context dependent and not equivalent to adding phosphate to NAD. No human intake inference. exposure: Nucleotide-bound conformational states evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nnt-structure-2019.abstract.txt", "locator": "Indexed abstract, reaction and structural mechanism", "start_char": 199, "end_char": 1759, "file_sha256": "edb35c2cdf2f57d604cb86da48665e5742d398f43c50f3e1622d161564c78a83", "text_sha256": "aa5063e57c35097c2fa2557ed9a7d61c3a411d90d0ded9b947525012520a5712"} [nnt-structure-2019] Structure and mechanism of mitochondrial proton-translocating transhydrogenase. (2019). https://pubmed.ncbi.nlm.nih.gov/31462775/ DOI: 10.1038/s41586-019-1519-2

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nnt-reverse-2015.abstract.txt", "locator": "Indexed abstract, pathological workload results", "start_char": 373, "end_char": 1028, "file_sha256": "88e6510d357946cd087e5af7ca3c9fdfd2ac22f2fb1851dd1164f176c5e39ce4", "text_sha256": "a8e2d67ccb1f5f041786aecfb33760602a804017dccfe41c54b34213ea0c6223"}

experimental_model

Mouse cardiac pressure-overload / pathological-demand experiments

exposure

Pathological cardiac metabolic demand

limitations

Context-dependent reversal, not genetic kinase failure or dietary niacin deficiency. Abstract-only extraction; do not generalize to all hearts or propose NNT inhibition clinically.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Mus musculus

plain_language

Under this high-workload condition Nnt used up NADPH instead of supplying it.

primary_references

[nnt-reverse-2015] Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure. (2015). https://pubmed.ncbi.nlm.nih.gov/26256392/ DOI: 10.1016/j.cmet.2015.07.008

tissue_or_cell_type

Heart

trigger_kind

machinery_impairment Imported condition classification; unverified.

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1016–1027

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse cardiac pressure-overload / pathological-demand experiments · source_derived_draft · unverified_draft

### b3-redox-nnt-reversal In the cardiac pathological-workload study, reverse-mode Nnt consumed NADPH while supporting NADH and ATP production. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Under this high-workload condition Nnt used up NADPH instead of supplying it. organism: Mus musculus tissue_or_cell_type: Heart experimental_model: Mouse cardiac pressure-overload / pathological-demand experiments limitations: Context-dependent reversal, not genetic kinase failure or dietary niacin deficiency. Abstract-only extraction; do not generalize to all hearts or propose NNT inhibition clinically. exposure: Pathological cardiac metabolic demand evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nnt-reverse-2015.abstract.txt", "locator": "Indexed abstract, pathological workload results", "start_char": 373, "end_char": 1028, "file_sha256": "88e6510d357946cd087e5af7ca3c9fdfd2ac22f2fb1851dd1164f176c5e39ce4", "text_sha256": "a8e2d67ccb1f5f041786aecfb33760602a804017dccfe41c54b34213ea0c6223"} [nnt-reverse-2015] Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure. (2015). https://pubmed.ncbi.nlm.nih.gov/26256392/ DOI: 10.1016/j.cmet.2015.07.008

experimental_model

Human AASS cloning, localization and familial hyperlysinemia genetics

limitations

Biochemical capacity does not quantify flux in every human tissue.

organism

Homo sapiens

plain_language

The second AASS activity opens the next lysine breakdown step.

primary_references

[sacksteder2000] Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia (2000). https://pmc.ncbi.nlm.nih.gov/articles/PMC1378037/ DOI: 10.1086/302919

tissue_or_cell_type

Mitochondrial matrix

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 84–92

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AASS cloning, localization and familial hyperlysinemia genetics · source_derived_draft · unverified_draft

### aass-saccharopine-dehydrogenase The AASS dehydrogenase domain oxidatively cleaves saccharopine, producing alpha-aminoadipate semialdehyde and glutamate with NAD+ reduction. Plain language: The second AASS activity opens the next lysine breakdown step. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Human AASS cloning, localization and familial hyperlysinemia genetics limitations: Biochemical capacity does not quantify flux in every human tissue. [sacksteder2000] Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia (2000). https://pmc.ncbi.nlm.nih.gov/articles/PMC1378037/ DOI: 10.1086/302919

experimental_model

Human ALDH7A1 biochemical and genetic study

limitations

Compartmental isoform distribution is not resolved by this claim.

organism

Homo sapiens

plain_language

Antiquitin clears the aldehyde intermediate.

primary_references

[luo2015] Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1 (2015). https://pubmed.ncbi.nlm.nih.gov/26260980/ DOI: 10.1021/acs.biochem.5b00754

tissue_or_cell_type

Lysine-catabolizing tissues

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 104–112

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ALDH7A1 biochemical and genetic study · source_derived_draft · unverified_draft

### aldh7a1-oxidation ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+. Plain language: Antiquitin clears the aldehyde intermediate. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Lysine-catabolizing tissues experimental_model: Human ALDH7A1 biochemical and genetic study limitations: Compartmental isoform distribution is not resolved by this claim. [luo2015] Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1 (2015). https://pubmed.ncbi.nlm.nih.gov/26260980/ DOI: 10.1021/acs.biochem.5b00754

experimental_model

Rat enzyme purification and recombinant human ALDH9 comparison

limitations

ALDH9A1 has additional aldehyde substrates.

organism

Homo sapiens

plain_language

An aldehyde is converted into the immediate carnitine precursor.

primary_references

[vaz2000] Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis (2000). https://pubmed.ncbi.nlm.nih.gov/10702312/ DOI: 10.1074/jbc.275.10.7390

tissue_or_cell_type

Cytosolic carnitine-biosynthesis reaction

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 197–205

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat enzyme purification and recombinant human ALDH9 comparison · source_derived_draft · unverified_draft

### aldh9a1-tmaba-oxidation Human ALDH9A1 oxidizes trimethylaminobutyraldehyde to gamma-butyrobetaine using NAD+. Plain language: An aldehyde is converted into the immediate carnitine precursor. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic carnitine-biosynthesis reaction experimental_model: Rat enzyme purification and recombinant human ALDH9 comparison limitations: ALDH9A1 has additional aldehyde substrates. [vaz2000] Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis (2000). https://pubmed.ncbi.nlm.nih.gov/10702312/ DOI: 10.1074/jbc.275.10.7390

experimental_model

Purified recombinant human HADH; substrate/product-cofactor crystal complexes

limitations

HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people.

organism

Homo sapiens

plain_language

The four-carbon hydroxy intermediate is oxidized to a keto intermediate.

primary_references

[barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200

tissue_or_cell_type

Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 367–375

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human HADH; substrate/product-cofactor crystal complexes · source_derived_draft · unverified_draft

### hadh-hydroxybutyryl-coa-oxidation The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH. Plain language: The four-carbon hydroxy intermediate is oxidized to a keto intermediate. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study experimental_model: Purified recombinant human HADH; substrate/product-cofactor crystal complexes limitations: HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people. [barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200

experimental_model

Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation

limitations

DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction.

organism

Homo sapiens

plain_language

A three-enzyme complex converts the carbon skeleton into glutaryl-CoA.

primary_references

[bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

tissue_or_cell_type

Mitochondrial matrix

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 125–134

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation · source_derived_draft · unverified_draft

### oxoadipate-dehydrogenase-complex DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation. Plain language: A three-enzyme complex converts the carbon skeleton into glutaryl-CoA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation limitations: DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction. [bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

evidence_access

Reactome curated reaction and its primary-study attribution

experimental_model

Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work.

limitations

Reversible reaction; redox state and compartment determine net direction.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

Ketone interconversion connects to niacin-derived redox chemistry.

primary_references

BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 128–134

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. · source_derived_draft · unverified_draft

## fast-bdh-reaction Ketone interconversion connects to niacin-derived redox chemistry. BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair. Model: Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. Limitations: Reversible reaction; redox state and compartment determine net direction. Evidence access: Reactome curated reaction and its primary-study attribution BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920

cross_nutrient

true

experimental_model

Human volunteer erythrocytes ex vivo

exposure

DHA challenge with or without 5 mM glucose

limitations

Metabolic support and transporter competition are different processes; this does not imply dietary sugar supplementation is needed.

nutrient_topic

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

organism

Homo sapiens

plain_language

Glucose metabolism helped sustain the reducing resources used to recycle vitamin C.

primary_references

[may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

tissue_or_cell_type

Erythrocytes

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteer erythrocytes ex vivo · source_derived_draft · unverified_draft

### vc-transport-rbc-glucose-support During DHA reduction by human erythrocytes, 5 mM D-glucose maintained GSH and NADH concentrations whereas NADPH still declined; without glucose all three fell. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose metabolism helped sustain the reducing resources used to recycle vitamin C. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human volunteer erythrocytes ex vivo limitations: Metabolic support and transporter competition are different processes; this does not imply dietary sugar supplementation is needed. exposure: DHA challenge with or without 5 mM glucose cross_nutrient: true [may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

evidence_span

{"source_cache": "artifacts/glutathione-research/7213635.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5", "start_char": 0, "end_char": 592, "text_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5"}

experimental_model

Product-inhibition kinetics

exposure

Forward and reverse reaction products

limitations

Kinetic mechanism; no evidence here for a dietary detoxification protocol.

nutrient_topic

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

organism

Human

plain_language

Glutathione carries formaldehyde through an enzyme-dependent route.

primary_references

[glutathione-p7213635] Product inhibition studies of human liver formaldehyde dehydrogenase. (1980). https://pubmed.ncbi.nlm.nih.gov/7213635/ DOI: 10.1016/0005-2744(80)90133-3

tissue_or_cell_type

Liver formaldehyde dehydrogenase

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1022–1033

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

### glutathione-adh5-formaldehyde Human liver enzyme kinetics supported NAD+-dependent processing of S-hydroxymethylglutathione to the S-formylglutathione/NADH products. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione carries formaldehyde through an enzyme-dependent route. organism: Human tissue_or_cell_type: Liver formaldehyde dehydrogenase experimental_model: Product-inhibition kinetics limitations: Kinetic mechanism; no evidence here for a dietary detoxification protocol. exposure: Forward and reverse reaction products evidence_span: {"source_cache": "artifacts/glutathione-research/7213635.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5", "start_char": 0, "end_char": 592, "text_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5"} [glutathione-p7213635] Product inhibition studies of human liver formaldehyde dehydrogenase. (1980). https://pubmed.ncbi.nlm.nih.gov/7213635/ DOI: 10.1016/0005-2744(80)90133-3

evidence_span

{"source_cache": "artifacts/molybdenum-research/20861021.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877", "start_char": 0, "end_char": 1557, "text_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877"}

experimental_model

Recombinant human mARC1/mARC2 biochemical and spectroscopic reconstitution

exposure

N-hydroxylated substrates; cofactor reconstitution

limitations

The 2010 paper could not identify the Mo-ligating cysteine; later structural/mutagenesis work resolves that point. Its earlier inference is not imported as current fact.

nutrient_topic

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

organism

Human proteins expressed in Escherichia coli

plain_language

Niacin, riboflavin, iron and molybdenum meet in one electron-transfer chain.

primary_references

[mo-p20861021] Biochemical and spectroscopic characterization of the human mitochondrial amidoxime reducing components hmARC-1 and hmARC-2 suggests the existence of a new molybdenum enzyme family in eukaryotes. (2010). https://pubmed.ncbi.nlm.nih.gov/20861021/ DOI: 10.1074/jbc.m110.169532

tissue_or_cell_type

Purified enzyme system

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 963–974

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human mARC1/mARC2 biochemical and spectroscopic reconstitution · source_derived_draft · unverified_draft

### mo-marc-fad-nadh The reconstituted mARC system used NADH/FAD-dependent cytochrome b5 reductase and heme-containing cytochrome b5. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Niacin, riboflavin, iron and molybdenum meet in one electron-transfer chain. organism: Human proteins expressed in Escherichia coli tissue_or_cell_type: Purified enzyme system experimental_model: Recombinant human mARC1/mARC2 biochemical and spectroscopic reconstitution limitations: The 2010 paper could not identify the Mo-ligating cysteine; later structural/mutagenesis work resolves that point. Its earlier inference is not imported as current fact. exposure: N-hydroxylated substrates; cofactor reconstitution evidence_span: {"source_cache": "artifacts/molybdenum-research/20861021.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877", "start_char": 0, "end_char": 1557, "text_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877"} [mo-p20861021] Biochemical and spectroscopic characterization of the human mitochondrial amidoxime reducing components hmARC-1 and hmARC-2 suggests the existence of a new molybdenum enzyme family in eukaryotes. (2010). https://pubmed.ncbi.nlm.nih.gov/20861021/ DOI: 10.1074/jbc.m110.169532

evidence_span

{"source_cache": "artifacts/molybdenum-research/24500710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b", "start_char": 0, "end_char": 1585, "text_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b"}

experimental_model

Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression

exposure

Reduced enzyme, nitrite, NADH/CYB5/CYB5R; pH 7.5 versus 6.5

limitations

Shows nitrite-reducing capacity; its share of NO production in normal people and response to mineral intake are not established.

nutrient_topic

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

organism

Homo sapiens proteins and HEK cells

plain_language

mARC1 can also make NO from nitrite under suitable conditions.

primary_references

[mo-p24500710] Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. (2014). https://pubmed.ncbi.nlm.nih.gov/24500710/ DOI: 10.1074/jbc.m114.555177

tissue_or_cell_type

Purified redox system and human cell model

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1028–1039

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression · source_derived_draft · unverified_draft

### mo-marc1-nitrite Reduced human mARC1 generated nitric oxide from nitrite in the reconstituted electron-transfer chain. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: mARC1 can also make NO from nitrite under suitable conditions. organism: Homo sapiens proteins and HEK cells tissue_or_cell_type: Purified redox system and human cell model experimental_model: Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression limitations: Shows nitrite-reducing capacity; its share of NO production in normal people and response to mineral intake are not established. exposure: Reduced enzyme, nitrite, NADH/CYB5/CYB5R; pH 7.5 versus 6.5 evidence_span: {"source_cache": "artifacts/molybdenum-research/24500710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b", "start_char": 0, "end_char": 1585, "text_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b"} [mo-p24500710] Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. (2014). https://pubmed.ncbi.nlm.nih.gov/24500710/ DOI: 10.1074/jbc.m114.555177

evidence_span

{"source_cache": "artifacts/molybdenum-research/24500710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b", "start_char": 0, "end_char": 1585, "text_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b"}

experimental_model

Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression

exposure

Reduced enzyme, nitrite, NADH/CYB5/CYB5R; pH 7.5 versus 6.5

limitations

Shows nitrite-reducing capacity; its share of NO production in normal people and response to mineral intake are not established.

nutrient_topic

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

organism

Homo sapiens proteins and HEK cells

plain_language

mARC2 shares this conditional NO-forming capability.

primary_references

[mo-p24500710] Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. (2014). https://pubmed.ncbi.nlm.nih.gov/24500710/ DOI: 10.1074/jbc.m114.555177

tissue_or_cell_type

Purified redox system and human cell model

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1041–1052

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression · source_derived_draft · unverified_draft

### mo-marc2-nitrite Reduced human mARC2 also catalyzed nitrite-to-NO conversion. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: mARC2 shares this conditional NO-forming capability. organism: Homo sapiens proteins and HEK cells tissue_or_cell_type: Purified redox system and human cell model experimental_model: Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression limitations: Shows nitrite-reducing capacity; its share of NO production in normal people and response to mineral intake are not established. exposure: Reduced enzyme, nitrite, NADH/CYB5/CYB5R; pH 7.5 versus 6.5 evidence_span: {"source_cache": "artifacts/molybdenum-research/24500710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b", "start_char": 0, "end_char": 1585, "text_sha256": "e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b"} [mo-p24500710] Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. (2014). https://pubmed.ncbi.nlm.nih.gov/24500710/ DOI: 10.1074/jbc.m114.555177

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/molybdenum-research/15273247.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2f73a9ca41e4d51b85d3a66ada08511055ce6ff7462beb0e7eaf21aadf37279", "start_char": 0, "end_char": 1606, "text_sha256": "d2f73a9ca41e4d51b85d3a66ada08511055ce6ff7462beb0e7eaf21aadf37279"}

experimental_model

Rat brain mitochondria/extracts, purified enzyme and Neuro-2a/PC12 cells

exposure

Micromolar sulfite exposure

limitations

Experimental substrate dependence; not a measurement of these effects in people with ordinary low molybdenum intake.

nutrient_topic

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

organism

Rattus norvegicus tissue; rodent cell lines

plain_language

A sulfur-metabolism disturbance can interrupt a separate fuel-processing enzyme.

primary_references

[mo-p15273247] A mechanism of sulfite neurotoxicity: direct inhibition of glutamate dehydrogenase. (2004). https://pubmed.ncbi.nlm.nih.gov/15273247/ DOI: 10.1074/jbc.m402759200

tissue_or_cell_type

Mitochondrial glutamate oxidation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1366–1377

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat brain mitochondria/extracts, purified enzyme and Neuro-2a/PC12 cells · source_derived_draft · unverified_draft

### mo-sulfite-gdh Sulfite inhibited rat-brain glutamate dehydrogenase and reduced glutamate-supported NADH production. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sulfur-metabolism disturbance can interrupt a separate fuel-processing enzyme. organism: Rattus norvegicus tissue; rodent cell lines tissue_or_cell_type: Mitochondrial glutamate oxidation experimental_model: Rat brain mitochondria/extracts, purified enzyme and Neuro-2a/PC12 cells limitations: Experimental substrate dependence; not a measurement of these effects in people with ordinary low molybdenum intake. exposure: Micromolar sulfite exposure evidence_span: {"source_cache": "artifacts/molybdenum-research/15273247.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2f73a9ca41e4d51b85d3a66ada08511055ce6ff7462beb0e7eaf21aadf37279", "start_char": 0, "end_char": 1606, "text_sha256": "d2f73a9ca41e4d51b85d3a66ada08511055ce6ff7462beb0e7eaf21aadf37279"} [mo-p15273247] A mechanism of sulfite neurotoxicity: direct inhibition of glutamate dehydrogenase. (2004). https://pubmed.ncbi.nlm.nih.gov/15273247/ DOI: 10.1074/jbc.m402759200

evidence_span

{"source_cache": "artifacts/molybdenum-research/37713777.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8092b2aa7328b59f0275dd8a37d2a2dbb5abb2a32236d0cab5fffcc1ddc671d", "start_char": 0, "end_char": 1579, "text_sha256": "18325172be489f8f4beae16c04dbc4f49f94c87186321e32aede61f27089c7c4"}

experimental_model

Recombinant human XDH variants with urate, superoxide and NO assays

exposure

Xanthine, oxygen and inorganic nitrite assays

limitations

Canonical electron-transfer mechanism stated in this primary article; not an experiment on dietary B2 or niacin depletion.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

Riboflavin-derived FAD, iron-sulfur centers and niacin-derived NAD work alongside molybdenum.

primary_references

[mo-p37713777] Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health? (2023). https://pubmed.ncbi.nlm.nih.gov/37713777/ DOI: 10.1016/j.redox.2023.102864

tissue_or_cell_type

Purified human enzyme

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 768–779

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human XDH variants with urate, superoxide and NO assays · source_derived_draft · unverified_draft

### mo-xdh-nad The XDH form transfers purine-derived electrons through its iron-sulfur centers and FAD to NAD+, producing NADH. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Riboflavin-derived FAD, iron-sulfur centers and niacin-derived NAD work alongside molybdenum. organism: Homo sapiens protein tissue_or_cell_type: Purified human enzyme experimental_model: Recombinant human XDH variants with urate, superoxide and NO assays limitations: Canonical electron-transfer mechanism stated in this primary article; not an experiment on dietary B2 or niacin depletion. exposure: Xanthine, oxygen and inorganic nitrite assays evidence_span: {"source_cache": "artifacts/molybdenum-research/37713777.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8092b2aa7328b59f0275dd8a37d2a2dbb5abb2a32236d0cab5fffcc1ddc671d", "start_char": 0, "end_char": 1579, "text_sha256": "18325172be489f8f4beae16c04dbc4f49f94c87186321e32aede61f27089c7c4"} [mo-p37713777] Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health? (2023). https://pubmed.ncbi.nlm.nih.gov/37713777/ DOI: 10.1016/j.redox.2023.102864

experimental_model

Purified-enzyme cofactor/substrate kinetics

limitations

Biochemical cofactor preference does not demonstrate a dietary niacin-deficiency visual phenotype.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

The reductase uses NADPH reducing power to convert retinal into retinol.

primary_references

[belyaeva-2005] Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids (2005). https://pubmed.ncbi.nlm.nih.gov/15865448/ DOI: 10.1021/bi050226k

tissue_or_cell_type

Recombinant enzyme preparation

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 778–787

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme cofactor/substrate kinetics · source_derived_draft · unverified_draft

### a-vision-rdh12-nadph Purified human RDH12 used NADPH for retinal reduction and had much lower apparent cofactor Km for NADP(H) than NAD(H). Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reductase uses NADPH reducing power to convert retinal into retinol. organism: Homo sapiens protein tissue_or_cell_type: Recombinant enzyme preparation experimental_model: Purified-enzyme cofactor/substrate kinetics limitations: Biochemical cofactor preference does not demonstrate a dietary niacin-deficiency visual phenotype. [belyaeva-2005] Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids (2005). https://pubmed.ncbi.nlm.nih.gov/15865448/ DOI: 10.1021/bi050226k

cross_nutrient

NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability.

evidence_location

Results: cofactor preference

experimental_model

Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.

exposure

1 micromolar retinol and 1 millimolar NAD+ versus NADP+.

limitations

Cofactor specificity does not establish an effect of dietary niacin deficiency.

nutrient_topic

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

organism

Homo sapiens protein in Spodoptera frugiperda Sf9 cells

outcome

Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays.

plain_language

RDH10 uses the oxidized nicotinamide cofactor to make retinal.

primary_references

[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

tissue_or_cell_type

Microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 487–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft

### va-rdh10-retinol-oxidation Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH10 uses the oxidized nicotinamide cofactor to make retinal. organism: Homo sapiens protein in Spodoptera frugiperda Sf9 cells tissue_or_cell_type: Microsomes experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Cofactor specificity does not establish an effect of dietary niacin deficiency. exposure: 1 micromolar retinol and 1 millimolar NAD+ versus NADP+. outcome: Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. evidence_location: Results: cofactor preference cross_nutrient: NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability. [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

evidence_access

Primary full text

experimental_model

Mouse C57BL/6J brown-fat mitochondria and reconstituted enzyme system.

limitations

An isolated-organelle assay does not prove that oral aspartate increases thermogenesis.

nutrient_topic

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

plain_language

The transport cycle linked a cytosolic redox pool to mitochondrial machinery.

primary_references

The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 322–328

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse C57BL/6J brown-fat mitochondria and reconstituted enzyme system. · source_derived_draft · unverified_draft

## l-aspartate-brown-shuttle-redox The transport cycle linked a cytosolic redox pool to mitochondrial machinery. Isolated mouse brown-fat mitochondria reconstituted with cytosolic shuttle enzymes oxidized extramitochondrial NADH in a glutamate-dependent manner. Model: Mouse C57BL/6J brown-fat mitochondria and reconstituted enzyme system. Limitations: An isolated-organelle assay does not prove that oral aspartate increases thermogenesis. Evidence access: Primary full text The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse Slc25a13-null hepatocytes with exogenous aralar expression.

limitations

Gene-expression rescue is not proof that oral aspartate or calcium corrects human citrin deficiency.

nutrient_topic

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

plain_language

A related carrier can substitute for part of the missing transport function in this model.

primary_references

Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning 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 · Mouse Slc25a13-null hepatocytes with exogenous aralar expression. · source_derived_draft · unverified_draft

## l-aspartate-citrin-aralar-rescue A related carrier can substitute for part of the missing transport function in this model. Exogenous aralar expression reversed the increased NADH/NAD+ ratio in hepatocytes from citrin-null mice. Model: Mouse Slc25a13-null hepatocytes with exogenous aralar expression. Limitations: Gene-expression rescue is not proof that oral aspartate or calcium corrects human citrin deficiency. Evidence access: Primary full text Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Isolated liver mitochondria from genetically modified mice.

limitations

Small ex vivo flux increment; not human therapeutic efficacy.

nutrient_topic

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

plain_language

A measurable transport rescue did not amount to proof of complete disease correction.

primary_references

Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 130–136

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated liver mitochondria from genetically modified mice. · source_derived_draft · unverified_draft

## l-aspartate-citrin-shuttle-rescue A measurable transport rescue did not amount to proof of complete disease correction. Liver-specific transgenic aralar expression increased residual shuttle activity in citrin-null mouse mitochondria by approximately 4–6 nmol per mg protein per minute. Model: Isolated liver mitochondria from genetically modified mice. Limitations: Small ex vivo flux increment; not human therapeutic efficacy. Evidence access: Primary full text Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human Jurkat-centered genetic and metabolic experiments.

limitations

Pyruvate is not a universally effective rescue for every respiratory or transaminase defect.

nutrient_topic

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

plain_language

Providing an electron acceptor did not bypass the need for functioning synthesis machinery.

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 58–64

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Jurkat-centered genetic and metabolic experiments. · source_derived_draft · unverified_draft

## l-aspartate-pyruvate-got1-gate Providing an electron acceptor did not bypass the need for functioning synthesis machinery. GOT1 loss prevented pyruvate from rescuing aspartate synthesis and proliferation during ETC dysfunction. Model: Human Jurkat-centered genetic and metabolic experiments. Limitations: Pyruvate is not a universally effective rescue for every respiratory or transaminase defect. 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

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Proliferating-cell perturbation and tracer study, including human NSCLC models.

limitations

Substrate availability in cell models is not evidence for benefits of oral L-aspartate.

nutrient_topic

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

plain_language

Aspartate demand for building material can compete with its participation in redox transfer.

primary_references

Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Proliferating-cell perturbation and tracer study, including human NSCLC models. · source_derived_draft · unverified_draft

## l-aspartate-shuttle-aspartate-availability Aspartate demand for building material can compete with its participation in redox transfer. Increasing aspartate availability enhanced malate–aspartate shuttle use and mitochondrial metabolism of glucose-derived pyruvate in proliferating cell experiments. Model: Proliferating-cell perturbation and tracer study, including human NSCLC models. Limitations: Substrate availability in cell models is not evidence for benefits of oral L-aspartate. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Human lung-cancer cell gene editing, metabolite ratios and carbon tracing.

limitations

A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured.

nutrient_topic

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

plain_language

Redox handling connects aspartate machinery to synthesis of another amino acid.

primary_references

Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 234–240

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. · source_derived_draft · unverified_draft

## l-aspartate-shuttle-serine-link Redox handling connects aspartate machinery to synthesis of another amino acid. Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models. Model: Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. Limitations: A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse T-cell genetic and redox-restoration experiments.

limitations

Not evidence that NAD metabolism is irrelevant in other cell states.

nutrient_topic

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

plain_language

Correcting one metabolic measurement did not fix the nitrogen-handling problem.

primary_references

The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 314–320

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse T-cell genetic and redox-restoration experiments. · source_derived_draft · unverified_draft

## l-aspartate-tcell-redox-insufficient Correcting one metabolic measurement did not fix the nitrogen-handling problem. Increasing the NAD+/NADH ratio did not restore the impaired antiviral T-cell response after Got1 loss in the tested chronic-infection setting. Model: Mouse T-cell genetic and redox-restoration experiments. Limitations: Not evidence that NAD metabolism is irrelevant in other cell states. Evidence access: Primary abstract The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5

cross_nutrient

Folate reduction uses nicotinamide reducing equivalents.

experimental_model

Recombinant human MTHFR; kinetics and structures.

limitations

Affinity does not quantify cellular flux.

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

MTHFR strongly preferred NADPH in this assay.

primary_references

[froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2

tissue_or_cell_type

Purified protein

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 435–445

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR; kinetics and structures. · source_derived_draft · unverified_draft

### folate-methyl-nadph-preference Purified full-length human MTHFR had apparent Km values of 35.5 micromolar for NADPH and 3760 micromolar for NADH. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTHFR strongly preferred NADPH in this assay. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human MTHFR; kinetics and structures. limitations: Affinity does not quantify cellular flux. cross_nutrient: Folate reduction uses nicotinamide reducing equivalents. [froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2

cross_nutrient

Nicotinamide cofactors connect folate chemistry to redox metabolism.

experimental_model

Purified recombinant enzyme

exposure

Assay conditions described in the linked primary study.

limitations

Cellular cofactor partition is not quantified.

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

This mitochondrial enzyme extracts electrons from folate-bound carbon.

primary_references

[shin-2017] Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (2017). https://pubmed.ncbi.nlm.nih.gov/29225823/ DOI: 10.1186/s40170-017-0173-0

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 812–823

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

### mthfd2-nad-oxidation Purified human MTHFD2 oxidizes 5,10-methylene-THF using NAD+ to form methenyl-THF and NADH. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mitochondrial enzyme extracts electrons from folate-bound carbon. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Purified recombinant enzyme limitations: Cellular cofactor partition is not quantified. exposure: Assay conditions described in the linked primary study. cross_nutrient: Nicotinamide cofactors connect folate chemistry to redox metabolism. [shin-2017] Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (2017). https://pubmed.ncbi.nlm.nih.gov/29225823/ DOI: 10.1186/s40170-017-0173-0

evidence_span

{"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"}

experimental_model

Freeze-clamped liver metabolite measurement in starved rats after ethanol

exposure

Single ethanol dose, sampled over 30 minutes in fed and starved animals

limitations

The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state.

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

Rat

plain_language

Burning alcohol floods the cell with the reduced form of the carrier that every other pathway needs oxidised.

primary_references

[alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387

tissue_or_cell_type

Liver

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 98–109

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Freeze-clamped liver metabolite measurement in starved rats after ethanol · source_derived_draft · unverified_draft

### alcohol-redox-shift Ethanol administration caused an immediate decrease in the NAD+/NADH ratio of both cytoplasm and mitochondria, which persisted over the 30 minutes studied. Condition category: normal 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: Burning alcohol floods the cell with the reduced form of the carrier that every other pathway needs oxidised. organism: Rat tissue_or_cell_type: Liver experimental_model: Freeze-clamped liver metabolite measurement in starved rats after ethanol limitations: The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state. exposure: Single ethanol dose, sampled over 30 minutes in fed and starved animals evidence_span: {"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"} [alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387