NADP+

evidence_span

{"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"}

experimental_model

Cryo-EM and structural comparison

exposure

Ligand-free and NADP/G6P-bound states

limitations

Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial.

nutrient_topic

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

organism

Human

plain_language

The same coenzyme also has a distinct structural regulatory role.

primary_references

[glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119

tissue_or_cell_type

Purified wild-type G6PD and D200N

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 775–786

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and structural comparison · source_derived_draft · unverified_draft

### glutathione-g6pd-structural-nadp Structural-site NADP+ binding ordered the G6PD C-terminal region and supported substrate binding and catalysis. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same coenzyme also has a distinct structural regulatory role. organism: Human tissue_or_cell_type: Purified wild-type G6PD and D200N experimental_model: Cryo-EM and structural comparison limitations: Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial. exposure: Ligand-free and NADP/G6P-bound states evidence_span: {"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"} [glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119

cross_nutrient

Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH.

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"}

experimental_model

Full-length recombinant human NADK; G6PD-coupled assay

exposure

5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C

limitations

Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.

nutrient_topic

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

organism

Homo sapiens

plain_language

The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP.

primary_references

[nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664

tissue_or_cell_type

Purified enzyme

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 831–843

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Full-length recombinant human NADK; G6PD-coupled assay · source_derived_draft · unverified_draft

### b3-redox-nadk-mgatp Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Full-length recombinant human NADK; G6PD-coupled assay limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: 5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C cross_nutrient: Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"} [nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664

cross_nutrient

Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage.

evidence_span

[{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}]

experimental_model

Purified His-tagged Δ62C5orf33/NADK2

exposure

TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C

limitations

Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.

nutrient_topic

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

organism

Homo sapiens

plain_language

The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+.

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 protein

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 871–883

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged Δ62C5orf33/NADK2 · source_derived_draft · unverified_draft

### b3-redox-nadk2-phosphorylation Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Purified His-tagged Δ62C5orf33/NADK2 limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C cross_nutrient: Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage. evidence_span: [{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}] [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

cross_nutrient

Folate polyglutamylation changes nicotinamide-cofactor use.

experimental_model

Purified recombinant enzyme

exposure

Mono- versus pentaglutamate folate substrates; controlled NAD(P)+ assays.

limitations

Kinetics do not establish dominant in vivo NADPH production.

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

The folate tail affects which electron carrier the enzyme uses.

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 825–836

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-nadp-polyglutamate Human MTHFD2 also uses NADP+ with methylene-THF pentaglutamate; NADP-linked activity increases relative to the monoglutamate assay. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The folate tail affects which electron carrier the enzyme uses. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Purified recombinant enzyme limitations: Kinetics do not establish dominant in vivo NADPH production. exposure: Mono- versus pentaglutamate folate substrates; controlled NAD(P)+ assays. cross_nutrient: Folate polyglutamylation changes nicotinamide-cofactor use. [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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Prevents equating altered tryptophan metabolism with universal niacin depletion.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements.

exposure

Experimental riboflavin-deficient diet

limitations

The abstract reports an aggregate red-cell readout; it does not resolve synthesis flux, other tissues or every NAD species.

nutrient_topic

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

organism

Papio species (baboon)

plain_language

The B2-related urine change did not establish a fall in this red-cell nucleotide pool.

primary_references

[verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/

tissue_or_cell_type

Erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1290–1302

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. · source_derived_draft · unverified_draft

### b2-baboon-pyridine-nucleotide-boundary Red-cell pyridine nucleotides decreased in pyridoxine-deficient baboons, but not in the riboflavin-deficient group. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B2-related urine change did not establish a fall in this red-cell nucleotide pool. organism: Papio species (baboon) tissue_or_cell_type: Erythrocytes experimental_model: Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. limitations: The abstract reports an aggregate red-cell readout; it does not resolve synthesis flux, other tissues or every NAD species. exposure: Experimental riboflavin-deficient diet cross_nutrient: Prevents equating altered tryptophan metabolism with universal niacin depletion. evidence_location: Abstract [verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/

cross_nutrient

B2-FAD and nicotinamide cofactors provide the upstream side of a selenium-containing reductase.

evidence_location

Abstract

experimental_model

Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation.

exposure

Purified-enzyme assay

limitations

Structure used a Sec-to-Cys mutant and oxidized NADP+; direct atom-level conclusions about wild-type selenium chemistry are limited.

nutrient_topic

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

organism

Rattus norvegicus protein expressed recombinantly

plain_language

Thioredoxin reductase has a flavin input side.

primary_references

[sandalova2001] Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. (2001). https://pubmed.ncbi.nlm.nih.gov/11481439/ DOI: 10.1073/pnas.171178698

tissue_or_cell_type

Purified recombinant enzyme; no intact tissue

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1346–1358

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation. · source_derived_draft · unverified_draft

### b2-txnrd1-fad-nadph-architecture The rat TXNRD1 Sec498Cys structure showed conserved FAD- and NADPH-binding architecture around the N-terminal redox center. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thioredoxin reductase has a flavin input side. organism: Rattus norvegicus protein expressed recombinantly tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Rat TXNRD1 Sec498Cys recombinant mutant with NADP+, 3.0-A crystallography and substrate-docking interpretation. limitations: Structure used a Sec-to-Cys mutant and oxidized NADP+; direct atom-level conclusions about wild-type selenium chemistry are limited. exposure: Purified-enzyme assay cross_nutrient: B2-FAD and nicotinamide cofactors provide the upstream side of a selenium-containing reductase. evidence_location: Abstract [sandalova2001] Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. (2001). https://pubmed.ncbi.nlm.nih.gov/11481439/ DOI: 10.1073/pnas.171178698

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human DLD1 cells; immunopurified mitochondrial fractions and enzyme-cycling assays.

limitations

A compartment-specific genetic manipulation is not equivalent to dietary niacin deficiency.

nutrient_topic

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

plain_language

The cofactor pool inside mitochondria can fail even when a whole-cell measurement looks adequate.

primary_references

Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 54–60

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human DLD1 cells; immunopurified mitochondrial fractions and enzyme-cycling assays. · source_derived_draft · unverified_draft

## l-proline-nadk2-pool The cofactor pool inside mitochondria can fail even when a whole-cell measurement looks adequate. CRISPR deletion of NADK2 in human DLD1 cells reduced mitochondrial NADP(H) by more than 80% while whole-cell NADP(H) was not similarly depleted. Model: Human DLD1 cells; immunopurified mitochondrial fractions and enzyme-cycling assays. Limitations: A compartment-specific genetic manipulation is not equivalent to dietary niacin deficiency. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491

evidence_access

Primary full text

experimental_model

Lu1205 cell fractionation and recombinant human PYCRL kinetics.

limitations

The melanoma routing pattern is not asserted to apply identically in every human tissue.

nutrient_topic

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

plain_language

The cytosolic version has different preferences from the mitochondrial enzymes.

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 30–36

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Lu1205 cell fractionation and recombinant human PYCRL kinetics. · source_derived_draft · unverified_draft

## l-proline-pycr3-reduction The cytosolic version has different preferences from the mitochondrial enzymes. Human PYCRL/PYCR3 localized predominantly to the cytosol in the tested melanoma cells and was more efficient with NADPH in the biochemical comparison. Model: Lu1205 cell fractionation and recombinant human PYCRL kinetics. Limitations: The melanoma routing pattern is not asserted to apply identically in every human tissue. 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_span

{"source_cache": "artifacts/boron-research/18516691.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fc4f02e11634c2a2d111a99ee4c6175fe8839a8f28152b656b3c29be6745206", "start_char": 0, "end_char": 1733, "text_sha256": "5fc4f02e11634c2a2d111a99ee4c6175fe8839a8f28152b656b3c29be6745206"}

experimental_model

Human prostate cancer cell culture and mass spectrometry

exposure

Boric acid 100–1,000 µM; methylboronic acid comparator

limitations

These are cell-culture exposures, including concentrations far above usual circulating levels. Adduct detection and calcium responses do not prove cancer prevention or direct channel binding.

nutrient_topic

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

organism

Human DU-145 cells; cell-free complex analysis

plain_language

At the tested concentrations, boric acid reduced several ways these cancer cells released stored calcium.

primary_references

[boron-p18516691] Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells. (2009). https://pubmed.ncbi.nlm.nih.gov/18516691/ DOI: 10.1007/s10565-008-9085-7

tissue_or_cell_type

Prostate cancer cells

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 274–285

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human prostate cancer cell culture and mass spectrometry · source_derived_draft · unverified_draft

### boron-nad-calcium-response Boric acid partly inhibited NAD+-evoked calcium transients at 250 µM and completely at 1,000 µM in DU-145 cells; NADP+-evoked and mechanical responses were inhibited at 1,000 µM. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: At the tested concentrations, boric acid reduced several ways these cancer cells released stored calcium. organism: Human DU-145 cells; cell-free complex analysis tissue_or_cell_type: Prostate cancer cells experimental_model: Human prostate cancer cell culture and mass spectrometry limitations: These are cell-culture exposures, including concentrations far above usual circulating levels. Adduct detection and calcium responses do not prove cancer prevention or direct channel binding. exposure: Boric acid 100–1,000 µM; methylboronic acid comparator evidence_span: {"source_cache": "artifacts/boron-research/18516691.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fc4f02e11634c2a2d111a99ee4c6175fe8839a8f28152b656b3c29be6745206", "start_char": 0, "end_char": 1733, "text_sha256": "5fc4f02e11634c2a2d111a99ee4c6175fe8839a8f28152b656b3c29be6745206"} [boron-p18516691] Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells. (2009). https://pubmed.ncbi.nlm.nih.gov/18516691/ DOI: 10.1007/s10565-008-9085-7

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"}

experimental_model

siRNA knockdown

exposure

Three days after siRNA transfection

limitations

Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.

nutrient_topic

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

organism

Homo sapiens

plain_language

Reducing the kinase reduced the mitochondrial capacity to make NADP+.

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

HEK293A mitochondrial fraction

trigger_kind

machinery_impairment Imported condition classification; unverified.

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 925–936

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

### b3-redox-nadk2-knockdown-activity NADK2 knockdown reduced measured mitochondrial-fraction NAD kinase activity to 47% of control in HEK293A cells. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the kinase reduced the mitochondrial capacity to make NADP+. organism: Homo sapiens tissue_or_cell_type: HEK293A mitochondrial fraction experimental_model: siRNA knockdown limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: Three days after siRNA transfection evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, genetic and fibroblast results", "start_char": 357, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "e468b1beee1be208d337cdf94488aca05296b2dd3fcbba587ca323b8db6d2c96"}

experimental_model

Patient-derived fibroblasts

exposure

Inherited NADK2 alteration

limitations

Single described patient context; mitochondrial NADP(H) shortage arose from kinase machinery impairment, not demonstrated dietary niacin shortage.

nutrient_topic

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

organism

Homo sapiens

plain_language

The genetic defect impaired the mitochondrial phosphorylated cofactor pool.

primary_references

[nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218

tissue_or_cell_type

Fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 964–975

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

### b3-redox-nadk2-patient-pool Patient fibroblasts bearing a pathogenic NADK2 alteration had reduced mitochondrial NADP(H). Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The genetic defect impaired the mitochondrial phosphorylated cofactor pool. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Patient-derived fibroblasts limitations: Single described patient context; mitochondrial NADP(H) shortage arose from kinase machinery impairment, not demonstrated dietary niacin shortage. exposure: Inherited NADK2 alteration evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, genetic and fibroblast results", "start_char": 357, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "e468b1beee1be208d337cdf94488aca05296b2dd3fcbba587ca323b8db6d2c96"} [nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218

cross_nutrient

Uses phosphate polymers in a magnesium-containing enzyme assay, not a dietary phosphorus intervention.

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 11596, "end_char": 12294, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "f371b72f3f7104e6b2b1f4f28ec55e04b18b931383b51a3258872db0809a10d9"}

experimental_model

Purified NADK2 Δ62

exposure

Metaphosphate, hexametaphosphate and tetrapolyphosphate tested

limitations

In vitro substrate capacity; physiological flux from polyphosphate in human mitochondria was not established. Monomeric phosphate is not interchangeable with these polymers.

nutrient_topic

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

organism

Homo sapiens

plain_language

The recombinant mitochondrial enzyme accepted some polyphosphate preparations in vitro.

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 885–897

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-polyphosphate Purified human NADK2 Δ62 also supported NADP+ formation using inorganic polyphosphate preparations as phosphate donors. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The recombinant mitochondrial enzyme accepted some polyphosphate preparations in vitro. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Purified NADK2 Δ62 limitations: In vitro substrate capacity; physiological flux from polyphosphate in human mitochondria was not established. Monomeric phosphate is not interchangeable with these polymers. exposure: Metaphosphate, hexametaphosphate and tetrapolyphosphate tested cross_nutrient: Uses phosphate polymers in a magnesium-containing enzyme assay, not a dietary phosphorus intervention. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 11596, "end_char": 12294, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "f371b72f3f7104e6b2b1f4f28ec55e04b18b931383b51a3258872db0809a10d9"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

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

cross_nutrient

Niacin (vitamin B3) (repleted_nutrient); L-Tryptophan (measured_precursor); Oxidized nicotinamide adenine dinucleotide phosphate (co_measured_pool)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"}

experimental_model

Controlled metabolic-unit feeding; seven men, 80 days

exposure

6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine

limitations

Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials.

nutrient_topic

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

organism

Homo sapiens

plain_language

Extra leucine did not block niacin recovery under this tested diet.

primary_references

[nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949

tissue_or_cell_type

Erythrocytes and plasma

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1135–1147

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding; seven men, 80 days · source_derived_draft · unverified_draft

### nia-clin-leucine-repletion Adding 7.8 g/day leucine during repletion did not change end-period erythrocyte NAD or NADP or plasma tryptophan in this study. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra leucine did not block niacin recovery under this tested diet. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and plasma experimental_model: Controlled metabolic-unit feeding; seven men, 80 days limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. exposure: 6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine cross_nutrient: Niacin (vitamin B3) (repleted_nutrient); L-Tryptophan (measured_precursor); Oxidized nicotinamide adenine dinucleotide phosphate (co_measured_pool) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"} [nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949

cross_nutrient

Nicotinamide adenine dinucleotide, oxidized (measured_pool); Oxidized nicotinamide adenine dinucleotide phosphate (separate_measured_pool)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/martens2018.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "6743a5d9ad919ee67fb74af7f173b24bda66943d9c8878d6bc3bb72c80b2c37e", "start_char": 14418, "end_char": 14971, "text_sha256": "412dc909ef2a01bb3f0b5c429c6b594e084262779bbf4e6ad4005f0f1edb8767"}

experimental_model

Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed

exposure

Nicotinamide riboside chloride 500 mg twice daily versus placebo, six weeks each

limitations

Small short trial, no formal washout, directional tests; secondary endpoints adjusted for multiple comparisons. PBMC NAD is not all-tissue NAD or evidence of lifespan extension.

nutrient_topic

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

organism

Homo sapiens

plain_language

NR raised NAD in sampled blood immune cells, while a matching rise in NADP was not established.

primary_references

[nia-clin-martens2018] Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29599478/ DOI: 10.1038/s41467-018-03421-7

tissue_or_cell_type

Peripheral blood mononuclear cells and vascular physiology

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1459–1471

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed · source_derived_draft · unverified_draft

### nia-clin-nr-pbmc Six weeks of NR increased PBMC NAD+ by approximately 60% relative to placebo; the NADP+ increase was not statistically significant. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR raised NAD in sampled blood immune cells, while a matching rise in NADP was not established. organism: Homo sapiens tissue_or_cell_type: Peripheral blood mononuclear cells and vascular physiology experimental_model: Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed limitations: Small short trial, no formal washout, directional tests; secondary endpoints adjusted for multiple comparisons. PBMC NAD is not all-tissue NAD or evidence of lifespan extension. exposure: Nicotinamide riboside chloride 500 mg twice daily versus placebo, six weeks each cross_nutrient: Nicotinamide adenine dinucleotide, oxidized (measured_pool); Oxidized nicotinamide adenine dinucleotide phosphate (separate_measured_pool) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/martens2018.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "6743a5d9ad919ee67fb74af7f173b24bda66943d9c8878d6bc3bb72c80b2c37e", "start_char": 14418, "end_char": 14971, "text_sha256": "412dc909ef2a01bb3f0b5c429c6b594e084262779bbf4e6ad4005f0f1edb8767"} [nia-clin-martens2018] Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29599478/ DOI: 10.1038/s41467-018-03421-7

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Oxidized nicotinamide adenine dinucleotide phosphate (measured_coenzyme)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"}

experimental_model

Controlled metabolic-unit feeding; seven men, 80 days

exposure

6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine

limitations

Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials.

nutrient_topic

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

organism

Homo sapiens

plain_language

The two coenzyme pools did not fall together; low niacin did not mean equal loss of NAD and NADP.

primary_references

[nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949

tissue_or_cell_type

Erythrocytes and plasma

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1121–1133

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding; seven men, 80 days · source_derived_draft · unverified_draft

### nia-clin-restriction-nadp Erythrocyte NADP remained relatively unchanged during the low-NE diets that depleted erythrocyte NAD. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two coenzyme pools did not fall together; low niacin did not mean equal loss of NAD and NADP. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and plasma experimental_model: Controlled metabolic-unit feeding; seven men, 80 days limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. exposure: 6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine cross_nutrient: Oxidized nicotinamide adenine dinucleotide phosphate (measured_coenzyme) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"} [nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949

experimental_model

Recombinant human AASS and isolated reductase domain

limitations

Reaction reversibility in vitro does not imply appreciable human lysine biosynthesis.

organism

Homo sapiens

plain_language

AASS starts the main lysine breakdown route.

primary_references

[leandro2022] Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1 (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9490328/ DOI: 10.1098/rsob.220179

tissue_or_cell_type

Mitochondrial matrix

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 74–82

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AASS and isolated reductase domain · source_derived_draft · unverified_draft

### aass-reductase The AASS reductase domain condenses lysine with 2-oxoglutarate using NADPH to form saccharopine. Plain language: AASS starts the main lysine breakdown route. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human AASS and isolated reductase domain limitations: Reaction reversibility in vitro does not imply appreciable human lysine biosynthesis. [leandro2022] Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1 (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9490328/ DOI: 10.1098/rsob.220179

experimental_model

Recombinant human CRYM and mammalian enzyme substrate assays

limitations

Catalytic capacity does not determine the route's quantitative contribution to human brain lysine clearance.

organism

Homo sapiens enzyme; ovine enzyme used for initial purification

plain_language

A ring-shaped intermediate can be reduced to pipecolate.

primary_references

[hallen2011] Mammalian forebrain ketimine reductase identified as mu-crystallin; potential regulation by thyroid hormones. (2011). https://pubmed.ncbi.nlm.nih.gov/21332720/ DOI: 10.1111/j.1471-4159.2011.07220.x [hallen2015] Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/mu-Crystallin Under Physiological Conditions. (2015). https://pubmed.ncbi.nlm.nih.gov/25931162/ DOI: 10.1007/s11064-015-1590-5

tissue_or_cell_type

Cytosolic enzyme; forebrain biochemical context

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 336–345

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CRYM and mammalian enzyme substrate assays · source_derived_draft · unverified_draft

### crym-p2c-reduction CRYM ketimine reductase reduces P2C to L-pipecolate using reduced nicotinamide cofactors. Plain language: A ring-shaped intermediate can be reduced to pipecolate. Condition category: normal organism: Homo sapiens enzyme; ovine enzyme used for initial purification tissue_or_cell_type: Cytosolic enzyme; forebrain biochemical context experimental_model: Recombinant human CRYM and mammalian enzyme substrate assays limitations: Catalytic capacity does not determine the route's quantitative contribution to human brain lysine clearance. [hallen2011] Mammalian forebrain ketimine reductase identified as mu-crystallin; potential regulation by thyroid hormones. (2011). https://pubmed.ncbi.nlm.nih.gov/21332720/ DOI: 10.1111/j.1471-4159.2011.07220.x [hallen2015] Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/mu-Crystallin Under Physiological Conditions. (2015). https://pubmed.ncbi.nlm.nih.gov/25931162/ DOI: 10.1007/s11064-015-1590-5

evidence_span

{"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"}

experimental_model

Cryo-EM and structural comparison

exposure

Ligand-free and NADP/G6P-bound states

limitations

Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial.

nutrient_topic

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

organism

Human

plain_language

The reducing power used in glutathione recycling has to be replenished.

primary_references

[glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119

tissue_or_cell_type

Purified wild-type G6PD and D200N

Glutathione: metabolism, signaling and nutrient connections (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 · Cryo-EM and structural comparison · source_derived_draft · unverified_draft

### glutathione-g6pd-nadph Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reducing power used in glutathione recycling has to be replenished. organism: Human tissue_or_cell_type: Purified wild-type G6PD and D200N experimental_model: Cryo-EM and structural comparison limitations: Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial. exposure: Ligand-free and NADP/G6P-bound states evidence_span: {"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"} [glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119

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

experimental_model

Recombinant p32/RDH5 activity assay

limitations

Cofactor specificity is biochemical; no niacin-deficiency phenotype was tested.

nutrient_topic

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

organism

Bos taurus protein; COS cells

plain_language

RDH5 oxidizes the cis alcohol into the visual chromophore.

primary_references

[simon-1995] The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases (1995). https://pubmed.ncbi.nlm.nih.gov/7836368/ DOI: 10.1074/jbc.270.3.1107

tissue_or_cell_type

RPE-derived enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 723–732

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant p32/RDH5 activity assay · source_derived_draft · unverified_draft

### a-vision-rdh5-oxidation Bovine RDH5 expressed in COS cells oxidized 11-cis-retinol using NAD+; NADP did not support the tested activity. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH5 oxidizes the cis alcohol into the visual chromophore. organism: Bos taurus protein; COS cells tissue_or_cell_type: RPE-derived enzyme experimental_model: Recombinant p32/RDH5 activity assay limitations: Cofactor specificity is biochemical; no niacin-deficiency phenotype was tested. [simon-1995] The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases (1995). https://pubmed.ncbi.nlm.nih.gov/7836368/ DOI: 10.1074/jbc.270.3.1107

cross_nutrient

NADPH supports a retinoid buffering reaction.

evidence_location

Figure 5 and Table 1

experimental_model

Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos.

exposure

DHRS3 coexpressed with RDH10; retinal plus NADPH.

limitations

Cofactor dependency is not a dietary niacin intervention.

nutrient_topic

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

organism

Homo sapiens proteins in Sf9 and HEK293 systems

outcome

RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH.

plain_language

This reverse step restrains retinal available for acid production.

primary_references

[va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257

tissue_or_cell_type

Microsomal/cellular retinoid system

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 516–529

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. · source_derived_draft · unverified_draft

### va-dhrs3-retinal-reduction RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This reverse step restrains retinal available for acid production. organism: Homo sapiens proteins in Sf9 and HEK293 systems tissue_or_cell_type: Microsomal/cellular retinoid system experimental_model: Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. limitations: Cofactor dependency is not a dietary niacin intervention. exposure: DHRS3 coexpressed with RDH10; retinal plus NADPH. outcome: RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. evidence_location: Figure 5 and Table 1 cross_nutrient: NADPH supports a retinoid buffering reaction. [va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257

cross_nutrient

CoA maturation enables the folate-to-NADPH reaction.

experimental_model

Recombinant enzyme activation assay

exposure

Assay conditions described in the linked primary study.

limitations

Figure 5 used stable dideazafolate analogue rather than physiological folate.

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

The installed arm enables oxidation of folate-bound carbon.

primary_references

[strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1059–1070

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

### aldh1l2-activation-folate-oxidation Phosphopantetheinylation restored recombinant ALDH1L2 folate dehydrogenase activity with NADPH formation. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The installed arm enables oxidation of folate-bound carbon. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Recombinant enzyme activation assay limitations: Figure 5 used stable dideazafolate analogue rather than physiological folate. exposure: Assay conditions described in the linked primary study. cross_nutrient: CoA maturation enables the folate-to-NADPH reaction. [strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008

cross_nutrient

Direct magnesium/phosphate requirement in folate oxidation.

experimental_model

Cofactor omission/addition assays

exposure

Assay conditions described in the linked primary study.

limitations

No dietary magnesium threshold follows from these assays.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Magnesium supports this NAD-linked folate reaction.

primary_references

[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 862–873

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition assays · source_derived_draft · unverified_draft

### rat-mthfd2l-magnesium-phosphate The NAD+-dependent rat MTHFD2L dehydrogenase assay requires magnesium in the presence of phosphate. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports this NAD-linked folate reaction. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Cofactor omission/addition assays limitations: No dietary magnesium threshold follows from these assays. exposure: Assay conditions described in the linked primary study. cross_nutrient: Direct magnesium/phosphate requirement in folate oxidation. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

experimental_model

Purified recombinant rat protein

exposure

Assay conditions described in the linked primary study.

limitations

Human ortholog flux was not measured.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

A second mitochondrial enzyme can use either electron carrier.

primary_references

[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 838–848

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

### rat-mthfd2l-oxidation Rat MTHFD2L catalyzes methylene-THF oxidation with either NAD+ or NADP+. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second mitochondrial enzyme can use either electron carrier. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Purified recombinant rat protein limitations: Human ortholog flux was not measured. exposure: Assay conditions described in the linked primary study. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

cross_nutrient

Direct magnesium/phosphate requirement in folate oxidation.

experimental_model

Cofactor omission/addition assays

exposure

Assay conditions described in the linked primary study.

limitations

No dietary magnesium threshold follows from these assays.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Phosphate is another required partner in the NAD-linked reaction.

primary_references

[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1321–1332

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition assays · source_derived_draft · unverified_draft

### rat-mthfd2l-phosphate-nad-requirement The NAD+-dependent rat MTHFD2L assay also requires phosphate in the presence of magnesium. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate is another required partner in the NAD-linked reaction. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Cofactor omission/addition assays limitations: No dietary magnesium threshold follows from these assays. exposure: Assay conditions described in the linked primary study. cross_nutrient: Direct magnesium/phosphate requirement in folate oxidation. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

cross_nutrient

Direct magnesium/phosphate requirement in folate oxidation.

experimental_model

Cofactor omission/addition assays

exposure

Assay conditions described in the linked primary study.

limitations

No dietary magnesium threshold follows from these assays.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

The same phosphate has the opposite effect with the alternative electron carrier.

primary_references

[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1334–1345

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition assays · source_derived_draft · unverified_draft

### rat-mthfd2l-phosphate-nadp-inhibition Inorganic phosphate inhibits the NADP+-dependent dehydrogenase activity of rat MTHFD2L. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same phosphate has the opposite effect with the alternative electron carrier. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Cofactor omission/addition assays limitations: No dietary magnesium threshold follows from these assays. exposure: Assay conditions described in the linked primary study. cross_nutrient: Direct magnesium/phosphate requirement in folate oxidation. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573

experimental_model

Purified rat liver cytosolic thioredoxin reductase and recombinant active-site variants.

limitations

This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.

organism

Rat protein and recombinant enzyme assays

Selenium: literature corrections and mechanism additions · lines 965–974

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Purified rat liver cytosolic thioredoxin reductase and recombinant active-site variants. · secondary_verified · secondary_verified

## txnrd1-reduces-txn1 TXNRD1 recharges thioredoxin so it can reduce other proteins. Cytosolic TXNRD1 uses NADPH-derived reducing equivalents to reduce oxidized thioredoxin through its flavin and C-terminal redox centers. Experimental model: Purified rat liver cytosolic thioredoxin reductase and recombinant active-site variants. Organism: Rat protein and recombinant enzyme assays Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Mammalian thioredoxin reductase: C-terminal redox center and selenium-to-sulfur substitution](https://pmc.ncbi.nlm.nih.gov/articles/PMC15961/)

cell_type

cardiac mitochondria

experimental_model

Redox perturbation and peroxide-emission assays

limitations

Functional relay; not every chemical step isolated here.

organism

mouse and guinea pig

Selenium: literature corrections and mechanism additions · lines 606–616

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Redox perturbation and peroxide-emission assays · secondary_verified · secondary_verified

## txnrd2-reduces-txn2 A selenium enzyme restores mitochondrial thioredoxin's reducing power. TXNRD2 uses NADPH-derived reducing equivalents to regenerate reduced TXN2. Organism: mouse and guinea pig Cell type: cardiac mitochondria Experimental model: Redox perturbation and peroxide-emission assays Limitations: Functional relay; not every chemical step isolated here. Primary reference: [Thioredoxin Reductase-2 Is Essential for Keeping Low Levels of H2O2 Emission from Isolated Heart Mitochondria](https://pubmed.ncbi.nlm.nih.gov/21832082/)