H2O

Where it participates (unsigned role)

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

   Human cystathionine beta-synthase / CBS → Cystathionine source_derived_draftungraded
   Experimental context and source evidence

   cross_nutrient

   Methionine-derived sulfur enters cysteine synthesis.

   experimental_model

   Recombinant truncated human CBS crystallography

   limitations

   Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency.

   nutrient_topic

   Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

   organism

   Homo sapiens

   plain_language

   This B6-dependent step channels homocysteine into transsulfuration.

   primary_references

   [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910

   tissue_or_cell_type

   Purified recombinant protein; no intact tissue

   Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–527

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

   ### b6-met-cbs-condensation PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step channels homocysteine into transsulfuration. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency. cross_nutrient: Methionine-derived sulfur enters cysteine synthesis. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910

   Complete structured claim and evidence

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

   Human kynureninase / KYNU → 3-Hydroxy-L-kynurenine source_derived_draftungraded
   Experimental context and source evidence

   cross_nutrient

   PLP-dependent KYNU follows the FAD-dependent KMO step, connecting B6 and B2 with tryptophan-niacin metabolism.

   existing_related_claim_ids

   ["5570a502-6ebf-5397-bf2a-0148727e7695"]

   experimental_model

   Recombinant human KYNU crystallography and biochemical characterization

   limitations

   KYNU does not directly make NAD; subsequent enzymes and dietary niacin also contribute.

   nutrient_topic

   Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

   organism

   Homo sapiens

   plain_language

   This B6-dependent step processes the product of upstream KMO chemistry.

   primary_references

   [b6-kynu-2007] Crystal Structure of Homo Sapiens Kynureninase (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC2531291/ DOI: 10.1021/bi0616697

   tissue_or_cell_type

   Purified recombinant protein; no intact tissue

   Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 885–896

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human KYNU crystallography and biochemical characterization · source_derived_draft · unverified_draft

   ### b6-met-kynu-hydrolysis Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step processes the product of upstream KMO chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human KYNU crystallography and biochemical characterization limitations: KYNU does not directly make NAD; subsequent enzymes and dietary niacin also contribute. cross_nutrient: PLP-dependent KYNU follows the FAD-dependent KMO step, connecting B6 and B2 with tryptophan-niacin metabolism. existing_related_claim_ids: ["5570a502-6ebf-5397-bf2a-0148727e7695"] [b6-kynu-2007] Crystal Structure of Homo Sapiens Kynureninase (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC2531291/ DOI: 10.1021/bi0616697

   Complete structured claim and evidence

3. Vasopressin increased apical AQP2 labeling and shifted AQP2 from intracellular vesicles toward the apical membrane.

   Arginine vasopressin / antidiuretic hormone → Apical collecting-duct aquaporin-2 abundance source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"}

   experimental_model

   Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy

   exposure

   Vasopressin addition and withdrawal

   limitations

   Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response.

   nutrient_topic

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

   organism

   Rat

   plain_language

   The kidney can retain more water by moving water channels to the cell surface.

   primary_references

   [sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013

   tissue_or_cell_type

   Inner medullary collecting duct

   Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 421–432

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy · source_derived_draft · unverified_draft

   ### sodium-avp-aqp2 Vasopressin increased apical AQP2 labeling and shifted AQP2 from intracellular vesicles toward the apical membrane. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney can retain more water by moving water channels to the cell surface. organism: Rat tissue_or_cell_type: Inner medullary collecting duct experimental_model: Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy limitations: Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response. exposure: Vasopressin addition and withdrawal evidence_span: {"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"} [sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013

   Complete structured claim and evidence

4. Water permeability rose during vasopressin exposure and fell after withdrawal in parallel with AQP2 redistribution.

   Arginine vasopressin / antidiuretic hormone → Collecting-duct osmotic water permeability source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"}

   experimental_model

   Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy

   exposure

   Vasopressin addition and withdrawal

   limitations

   Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response.

   nutrient_topic

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

   organism

   Rat

   plain_language

   This is a water-control mechanism that must be considered when interpreting blood sodium.

   primary_references

   [sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013

   tissue_or_cell_type

   Inner medullary collecting duct

   Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 434–445

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy · source_derived_draft · unverified_draft

   ### sodium-avp-water Water permeability rose during vasopressin exposure and fell after withdrawal in parallel with AQP2 redistribution. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a water-control mechanism that must be considered when interpreting blood sodium. organism: Rat tissue_or_cell_type: Inner medullary collecting duct experimental_model: Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy limitations: Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response. exposure: Vasopressin addition and withdrawal evidence_span: {"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"} [sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013

   Complete structured claim and evidence

5. Weight gain during the marathon was independently associated with hyponatremia, odds ratio 4.2 (95% CI 2.2–8.2).

   Weight gain during endurance exercise → Plasma or serum sodium concentration source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/sodium-research/15829535.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bf7f638ff3cfcad3d43536a75ffedf40a2ef726f783922f3169c9252c12a8e5", "start_char": 0, "end_char": 1893, "text_sha256": "9bf7f638ff3cfcad3d43536a75ffedf40a2ef726f783922f3169c9252c12a8e5"}

   experimental_model

   Prospective marathon cohort with prerace/postrace weights and blood sampling

   exposure

   2002 Boston Marathon; 488 usable finish-line blood samples

   limitations

   Observational associations and sampling limitations; fluid composition was not independently associated. Not a treatment protocol or pure dietary-depletion study.

   nutrient_topic

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

   organism

   Human runners

   plain_language

   A low sodium concentration can accompany gaining water rather than simply losing salt.

   primary_references

   [sodium-p15829535] Hyponatremia among runners in the Boston Marathon. (2005). https://pubmed.ncbi.nlm.nih.gov/15829535/ DOI: 10.1056/nejmoa043901

   tissue_or_cell_type

   Systemic water/sodium balance

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1006–1017

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective marathon cohort with prerace/postrace weights and blood sampling · source_derived_draft · unverified_draft

   ### sodium-marathon-weight Weight gain during the marathon was independently associated with hyponatremia, odds ratio 4.2 (95% CI 2.2–8.2). Condition category: biomarker_context nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low sodium concentration can accompany gaining water rather than simply losing salt. organism: Human runners tissue_or_cell_type: Systemic water/sodium balance experimental_model: Prospective marathon cohort with prerace/postrace weights and blood sampling limitations: Observational associations and sampling limitations; fluid composition was not independently associated. Not a treatment protocol or pure dietary-depletion study. exposure: 2002 Boston Marathon; 488 usable finish-line blood samples evidence_span: {"source_cache": "artifacts/sodium-research/15829535.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bf7f638ff3cfcad3d43536a75ffedf40a2ef726f783922f3169c9252c12a8e5", "start_char": 0, "end_char": 1893, "text_sha256": "9bf7f638ff3cfcad3d43536a75ffedf40a2ef726f783922f3169c9252c12a8e5"} [sodium-p15829535] Hyponatremia among runners in the Boston Marathon. (2005). https://pubmed.ncbi.nlm.nih.gov/15829535/ DOI: 10.1056/nejmoa043901

   Complete structured claim and evidence

6. Hyponatremia below 130 mmol/L occurred in 29/142 versus 16/150 participants receiving reduced-osmolarity versus standard ORS; affected participants were symptom-free.

   Oral rehydration solutions (formulation specified per study) → Plasma or serum sodium concentration source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/sodium-research/10440307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969", "start_char": 0, "end_char": 2141, "text_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969"}

   experimental_model

   Randomized double-blind comparison in 300 adults with severe cholera

   exposure

   Reduced-osmolarity versus then-standard WHO oral rehydration solution

   limitations

   Historical formulation comparison; not a current formulation recommendation. Both sodium and other solution properties changed; no isolated sodium effect.

   nutrient_topic

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

   organism

   Human

   plain_language

   Replacing fluid is not just replacing water: solution composition affected blood sodium.

   primary_references

   [sodium-p10440307] Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440307/ DOI: 10.1016/s0140-6736(98)09332-5

   tissue_or_cell_type

   Intestinal fluid loss and serum sodium

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1045–1056

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind comparison in 300 adults with severe cholera · source_derived_draft · unverified_draft

   ### sodium-ors-sodium Hyponatremia below 130 mmol/L occurred in 29/142 versus 16/150 participants receiving reduced-osmolarity versus standard ORS; affected participants were symptom-free. Condition category: biomarker_context nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing fluid is not just replacing water: solution composition affected blood sodium. organism: Human tissue_or_cell_type: Intestinal fluid loss and serum sodium experimental_model: Randomized double-blind comparison in 300 adults with severe cholera limitations: Historical formulation comparison; not a current formulation recommendation. Both sodium and other solution properties changed; no isolated sodium effect. exposure: Reduced-osmolarity versus then-standard WHO oral rehydration solution evidence_span: {"source_cache": "artifacts/sodium-research/10440307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969", "start_char": 0, "end_char": 2141, "text_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969"} [sodium-p10440307] Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440307/ DOI: 10.1016/s0140-6736(98)09332-5

   Complete structured claim and evidence

7. The 6-g/day salt increase reduced free-water clearance while increasing urine osmolyte excretion.

   Sodium chloride → Renal free-water clearance source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sodium-research/28414302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "099d2bd468b387701a756371dde0732e2eba2b5d15d02948a99fc96c3df3046d", "start_char": 0, "end_char": 2118, "text_sha256": "099d2bd468b387701a756371dde0732e2eba2b5d15d02948a99fc96c3df3046d"}

   experimental_model

   Two controlled confinement studies lasting 105 and 205 days, totaling 10 men

   exposure

   6, 9 and 12 g/day salt; other nutrients held constant

   limitations

   Small all-male long-duration study; reduced free-water clearance is not creation of water. Do not extrapolate to acute salt ingestion, all populations or immune effects.

   nutrient_topic

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

   organism

   Human healthy men

   plain_language

   The kidneys adjusted water conservation during sustained salt exposure.

   primary_references

   [sodium-p28414302] Increased salt consumption induces body water conservation and decreases fluid intake. (2017). https://pubmed.ncbi.nlm.nih.gov/28414302/ DOI: 10.1172/jci88530

   tissue_or_cell_type

   Whole-body water and osmolyte balance

   Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1136–1147

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two controlled confinement studies lasting 105 and 205 days, totaling 10 men · source_derived_draft · unverified_draft

   ### sodium-salt-water-clearance The 6-g/day salt increase reduced free-water clearance while increasing urine osmolyte excretion. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidneys adjusted water conservation during sustained salt exposure. organism: Human healthy men tissue_or_cell_type: Whole-body water and osmolyte balance experimental_model: Two controlled confinement studies lasting 105 and 205 days, totaling 10 men limitations: Small all-male long-duration study; reduced free-water clearance is not creation of water. Do not extrapolate to acute salt ingestion, all populations or immune effects. exposure: 6, 9 and 12 g/day salt; other nutrients held constant evidence_span: {"source_cache": "artifacts/sodium-research/28414302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "099d2bd468b387701a756371dde0732e2eba2b5d15d02948a99fc96c3df3046d", "start_char": 0, "end_char": 2118, "text_sha256": "099d2bd468b387701a756371dde0732e2eba2b5d15d02948a99fc96c3df3046d"} [sodium-p28414302] Increased salt consumption induces body water conservation and decreases fluid intake. (2017). https://pubmed.ncbi.nlm.nih.gov/28414302/ DOI: 10.1172/jci88530

   Complete structured claim and evidence

8. ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization.

   Inorganic pyrophosphate → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
   Experimental context and source evidence

   compartment_description

   Extracellular matrix and vesicle surface

   experimental_model

   Genetic and ex vivo pyrophosphate/mineralization experiments

   limitations

   Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP.

   nutrient_topic

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

   organism

   Mus musculus

   plain_language

   TNAP removes a local brake on calcium phosphate crystal growth.

   primary_references

   [hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399

   tissue_or_cell_type

   Osteoblast matrix and matrix vesicles

   Calcium: mechanism-first literature curation (2026-09-17) · lines 931–941

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and ex vivo pyrophosphate/mineralization experiments · source_derived_draft · unverified_draft

   ### alpl-pyrophosphate-hydrolysis ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: TNAP removes a local brake on calcium phosphate crystal growth. organism: Mus musculus tissue_or_cell_type: Osteoblast matrix and matrix vesicles experimental_model: Genetic and ex vivo pyrophosphate/mineralization experiments limitations: Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP. compartment_description: Extracellular matrix and vesicle surface [hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399

   Complete structured claim and evidence

9. ENPP1 converts extracellular ATP into AMP and PPi; ANKH-expressing cells lacking ENPP1 released ATP without the accompanying PPi accumulation.

   ATP → Inorganic pyrophosphate source_derived_draftungraded
   Experimental context and source evidence

   compartment_description

   Extracellular space

   experimental_model

   ENPP1-proficient versus deficient cells

   limitations

   Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate.

   nutrient_topic

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

   organism

   Homo sapiens

   plain_language

   An extracellular enzyme converts exported ATP into a mineralization inhibitor.

   primary_references

   [szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528

   tissue_or_cell_type

   HEK293 extracellular medium

   Calcium: mechanism-first literature curation (2026-09-17) · lines 1012–1022

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ENPP1-proficient versus deficient cells · source_derived_draft · unverified_draft

   ### enpp1-atp-to-pyrophosphate ENPP1 converts extracellular ATP into AMP and PPi; ANKH-expressing cells lacking ENPP1 released ATP without the accompanying PPi accumulation. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An extracellular enzyme converts exported ATP into a mineralization inhibitor. organism: Homo sapiens tissue_or_cell_type: HEK293 extracellular medium experimental_model: ENPP1-proficient versus deficient cells limitations: Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate. compartment_description: Extracellular space [szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528

   Complete structured claim and evidence

10. Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline.

    Phosphocholine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
    Experimental context and source evidence

    experimental_model

    Purified-enzyme substrate assay

    limitations

    This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor.

    nutrient_topic

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

    organism

    Homo sapiens

    plain_language

    A second phospholipid-headgroup metabolite can supply phosphate.

    primary_references

    [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511

    tissue_or_cell_type

    Recombinant enzyme

    Calcium: mechanism-first literature curation (2026-09-17) · lines 908–917

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

    ### phospho1-phosphocholine-hydrolysis Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second phospholipid-headgroup metabolite can supply phosphate. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified-enzyme substrate assay limitations: This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511

    Complete structured claim and evidence

11. Human PHOSPHO1 hydrolyzes phosphoethanolamine, releasing inorganic phosphate and ethanolamine; the enzyme requires Mg2+ in the assay.

    Phosphoethanolamine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
    Experimental context and source evidence

    experimental_model

    Purified-enzyme substrate assay

    limitations

    Catalytic capacity does not quantify phosphate supply in vivo; Pi denotes pH-dependent protonation states.

    nutrient_topic

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

    organism

    Homo sapiens

    plain_language

    PHOSPHO1 can release phosphate from a membrane-headgroup metabolite.

    primary_references

    [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511

    tissue_or_cell_type

    Recombinant enzyme; mineralizing-cell context

    Calcium: mechanism-first literature curation (2026-09-17) · lines 897–906

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

    ### phospho1-phosphoethanolamine-hydrolysis Human PHOSPHO1 hydrolyzes phosphoethanolamine, releasing inorganic phosphate and ethanolamine; the enzyme requires Mg2+ in the assay. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PHOSPHO1 can release phosphate from a membrane-headgroup metabolite. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme; mineralizing-cell context experimental_model: Purified-enzyme substrate assay limitations: Catalytic capacity does not quantify phosphate supply in vivo; Pi denotes pH-dependent protonation states. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511

    Complete structured claim and evidence

12. Principal-cell Atg7 deletion worsened urine-concentrating impairment during potassium depletion rather than rescuing it.

    Principal-cell Atg7 deletion → Renal urine concentrating capacity source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    endpoint

    Principal-cell Atg7 deletion worsened urine-concentrating impairment during potassium depletion rather than rescuing it.

    experimental-exposure

    Principal-cell Atg7 conditional knockout and floxed control mice on normal or potassium-free diet for two weeks.

    experimental_model

    Principal-cell Atg7 conditional knockout and floxed control mice on normal or potassium-free diet for two weeks.

    limitations

    Knockout already altered basal urine concentration and caused compensatory degradation changes; this is not evidence against every role for autophagy.

    nutrient_topic

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

    organism

    Mus musculus

    plain_language

    Blocking one protein-disposal pathway did not restore water balance; channel phosphorylation and localization still mattered.

    primary_references

    [kim-2019-atg7-aqp2] Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia (2019). https://www.nature.com/articles/s41598-019-39702-4 DOI: 10.1038/s41598-019-39702-4

    tissue_or_cell_type

    collecting-duct principal cells

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1425–1436

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Principal-cell Atg7 conditional knockout and floxed control mice on normal or potassium-free diet for two weeks. · source_derived_draft · unverified_draft

    ### atg7-loss-worsens-hypokalemic-concentrating-defect Principal-cell Atg7 deletion worsened urine-concentrating impairment during potassium depletion rather than rescuing it. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking one protein-disposal pathway did not restore water balance; channel phosphorylation and localization still mattered. organism: Mus musculus tissue_or_cell_type: collecting-duct principal cells experimental_model: Principal-cell Atg7 conditional knockout and floxed control mice on normal or potassium-free diet for two weeks. limitations: Knockout already altered basal urine concentration and caused compensatory degradation changes; this is not evidence against every role for autophagy. experimental-exposure: Principal-cell Atg7 conditional knockout and floxed control mice on normal or potassium-free diet for two weeks. endpoint: Principal-cell Atg7 deletion worsened urine-concentrating impairment during potassium depletion rather than rescuing it. [kim-2019-atg7-aqp2] Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia (2019). https://www.nature.com/articles/s41598-019-39702-4 DOI: 10.1038/s41598-019-39702-4

    Complete structured claim and evidence

13. After one day of potassium deprivation, AQP2 localized in autophagic compartments in rat inner medullary collecting-duct cells.

    Potassium → AQP2 localization in autophagic compartments source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    endpoint

    After one day of potassium deprivation, AQP2 localized in autophagic compartments in rat inner medullary collecting-duct cells.

    experimental-exposure

    Rats fed potassium-free diet for one day; IMCD proteomics, immunoblotting, immunogold electron microscopy, and refeeding.

    experimental_model

    Rats fed potassium-free diet for one day; IMCD proteomics, immunoblotting, immunogold electron microscopy, and refeeding.

    limitations

    Autophagy inhibition was not performed; colocalization and recovery do not establish that autophagic AQP2 degradation alone caused polyuria.

    nutrient_topic

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

    organism

    Rattus norvegicus

    plain_language

    Water-channel disposal began early, alongside AQP2 loss.

    primary_references

    [khositseth-2015-aqp2] Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus (2015). https://www.nature.com/articles/srep18311 DOI: 10.1038/srep18311

    tissue_or_cell_type

    inner medullary collecting duct

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1399–1410

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats fed potassium-free diet for one day; IMCD proteomics, immunoblotting, immunogold electron microscopy, and refeeding. · source_derived_draft · unverified_draft

    ### early-k-deprivation-aqp2-autophagic-localization After one day of potassium deprivation, AQP2 localized in autophagic compartments in rat inner medullary collecting-duct cells. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Water-channel disposal began early, alongside AQP2 loss. organism: Rattus norvegicus tissue_or_cell_type: inner medullary collecting duct experimental_model: Rats fed potassium-free diet for one day; IMCD proteomics, immunoblotting, immunogold electron microscopy, and refeeding. limitations: Autophagy inhibition was not performed; colocalization and recovery do not establish that autophagic AQP2 degradation alone caused polyuria. experimental-exposure: Rats fed potassium-free diet for one day; IMCD proteomics, immunoblotting, immunogold electron microscopy, and refeeding. endpoint: After one day of potassium deprivation, AQP2 localized in autophagic compartments in rat inner medullary collecting-duct cells. [khositseth-2015-aqp2] Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus (2015). https://www.nature.com/articles/srep18311 DOI: 10.1038/srep18311

    Complete structured claim and evidence

14. Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts.

    Potassium → Aquaporin-2 / AQP2 source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    endpoint

    Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts.

    experimental-exposure

    Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding.

    experimental_model

    Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding.

    limitations

    Parallel changes and refeeding support reversibility, but no AQP2-specific rescue isolated its complete contribution.

    nutrient_topic

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

    organism

    Rattus norvegicus

    plain_language

    Less water-channel protein accompanied the concentrating defect.

    primary_references

    [marples-1996-aqp2] Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex (1996). https://pubmed.ncbi.nlm.nih.gov/8621781/ DOI: 10.1172/JCI118628

    tissue_or_cell_type

    cortical and inner medullary collecting ducts

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1386–1397

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding. · source_derived_draft · unverified_draft

    ### k-depletion-aqp2-abundance Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less water-channel protein accompanied the concentrating defect. organism: Rattus norvegicus tissue_or_cell_type: cortical and inner medullary collecting ducts experimental_model: Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding. limitations: Parallel changes and refeeding support reversibility, but no AQP2-specific rescue isolated its complete contribution. experimental-exposure: Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding. endpoint: Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts. [marples-1996-aqp2] Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex (1996). https://pubmed.ncbi.nlm.nih.gov/8621781/ DOI: 10.1172/JCI118628

    Complete structured claim and evidence

15. Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice.

    Potassium → Ser256-phosphorylated AQP2 source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    nutrient_deficiency Imported condition classification; unverified.

    endpoint

    Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice.

    experimental-exposure

    Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements.

    experimental_model

    Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements.

    limitations

    Sex and segment influenced severity; this does not establish a universal human plasma-potassium threshold or a unique responsible kinase.

    nutrient_topic

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

    organism

    Mus musculus

    plain_language

    The channel activation/trafficking state changed even where total protein loss was less marked.

    primary_references

    [al-qusairi-2021-vasopressin] Rapid development of vasopressin resistance in dietary K+ deficiency (2021). https://pubmed.ncbi.nlm.nih.gov/33749322/ DOI: 10.1152/ajprenal.00655.2020

    tissue_or_cell_type

    cortical and medullary collecting duct

    trigger_kind

    nutrient_deficiency Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1412–1423

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements. · source_derived_draft · unverified_draft

    ### k-restriction-lowers-aqp2-ser256 Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel activation/trafficking state changed even where total protein loss was less marked. organism: Mus musculus tissue_or_cell_type: cortical and medullary collecting duct experimental_model: Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements. limitations: Sex and segment influenced severity; this does not establish a universal human plasma-potassium threshold or a unique responsible kinase. experimental-exposure: Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements. endpoint: Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice. [al-qusairi-2021-vasopressin] Rapid development of vasopressin resistance in dietary K+ deficiency (2021). https://pubmed.ncbi.nlm.nih.gov/33749322/ DOI: 10.1152/ajprenal.00655.2020

    Complete structured claim and evidence

16. X-ray absorption analysis of human CA2 supported a zinc site with three histidine nitrogen ligands and most likely one water/hydroxide oxygen ligand in both isolated and reconstituted enzyme.

    Zinc(II) ion → Human carbonic anhydrase II / CA2 source_derived_draftungraded
    Experimental context and source evidence

    cross_nutrient

    false

    experimental_model

    Purified recombinant human CA2; metal reconstitution, ITC and X-ray absorption spectroscopy

    exposure

    Zn K-edge XANES and EXAFS on isolated and zinc-reconstituted recombinant CA2.

    limitations

    Coordination assignment is spectroscopic; the oxygen ligand is most likely solvent-derived, not an independently measured dietary effect.

    nutrient_topic

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

    organism

    Homo sapiens

    plain_language

    CA2 holds zinc with three histidines and a water-derived ligand at its active site.

    primary_references

    [zinc-enz-ca2-coordination2012] Revisiting zinc coordination in human carbonic anhydrase II. (2012). https://pubmed.ncbi.nlm.nih.gov/23030313/ DOI: 10.1021/ic301645j

    tissue_or_cell_type

    Purified protein; cell-free assay

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 651–662

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human CA2; metal reconstitution, ITC and X-ray absorption spectroscopy · source_derived_draft · unverified_draft

    ### zinc-enz-ca2-coordination X-ray absorption analysis of human CA2 supported a zinc site with three histidine nitrogen ligands and most likely one water/hydroxide oxygen ligand in both isolated and reconstituted enzyme. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: CA2 holds zinc with three histidines and a water-derived ligand at its active site. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified recombinant human CA2; metal reconstitution, ITC and X-ray absorption spectroscopy limitations: Coordination assignment is spectroscopic; the oxygen ligand is most likely solvent-derived, not an independently measured dietary effect. exposure: Zn K-edge XANES and EXAFS on isolated and zinc-reconstituted recombinant CA2. cross_nutrient: false [zinc-enz-ca2-coordination2012] Revisiting zinc coordination in human carbonic anhydrase II. (2012). https://pubmed.ncbi.nlm.nih.gov/23030313/ DOI: 10.1021/ic301645j

    Complete structured claim and evidence

17. Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively.

    Human carbonic anhydrase VI / CA6 → Bicarbonate ion source_derived_draftungraded
    Experimental context and source evidence

    cross_nutrient

    false

    experimental_model

    Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology

    exposure

    Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk.

    limitations

    Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations.

    nutrient_topic

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

    organism

    Homo sapiens

    plain_language

    Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate.

    primary_references

    [zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9

    tissue_or_cell_type

    Human saliva and breast milk; purified enzyme assay

    Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 664–675

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology · source_derived_draft · unverified_draft

    ### zinc-enz-ca6-hydration Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate. organism: Homo sapiens tissue_or_cell_type: Human saliva and breast milk; purified enzyme assay experimental_model: Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology limitations: Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations. exposure: Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk. cross_nutrient: false [zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9

    Complete structured claim and evidence

18. Human CD38 also hydrolyzes cyclic ADP-ribose to ADP-ribose.

    Human CD38 → Cyclic ADP-ribose source_derived_draftungraded
    Experimental context and source evidence

    cross_nutrient

    false

    evidence_span

    {"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"}

    experimental_model

    Biochemical characterization of human CD38

    exposure

    Cyclic ADP-ribose substrate

    limitations

    Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes.

    nutrient_topic

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

    organism

    Human

    plain_language

    CD38 also breaks down cyclic ADP-ribose.

    primary_references

    [b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383

    tissue_or_cell_type

    Cell-free enzyme preparation

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 593–605

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical characterization of human CD38 · source_derived_draft · unverified_draft

    ### b3-cons-cd38-cadpr-hydrolysis Human CD38 also hydrolyzes cyclic ADP-ribose to ADP-ribose. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CD38 also breaks down cyclic ADP-ribose. organism: Human tissue_or_cell_type: Cell-free enzyme preparation experimental_model: Biochemical characterization of human CD38 limitations: Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes. exposure: Cyclic ADP-ribose substrate cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"} [b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383

    Complete structured claim and evidence

19. Human CD38 hydrolyzes NAD+ to free ADP-ribose and nicotinamide.

    Human CD38 → NAD+ source_derived_draftungraded
    Experimental context and source evidence

    cross_nutrient

    false

    evidence_span

    {"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"}

    experimental_model

    Biochemical characterization of human CD38

    exposure

    NAD+ as substrate

    limitations

    Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes.

    nutrient_topic

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

    organism

    Human

    plain_language

    CD38 can break NAD into ADP-ribose and nicotinamide.

    primary_references

    [b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383

    tissue_or_cell_type

    Cell-free enzyme preparation

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 565–577

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical characterization of human CD38 · source_derived_draft · unverified_draft

    ### b3-cons-cd38-hydrolysis Human CD38 hydrolyzes NAD+ to free ADP-ribose and nicotinamide. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CD38 can break NAD into ADP-ribose and nicotinamide. organism: Human tissue_or_cell_type: Cell-free enzyme preparation experimental_model: Biochemical characterization of human CD38 limitations: Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes. exposure: NAD+ as substrate cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"} [b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383

    Complete structured claim and evidence

20. Dehydration can promote lithium retention and toxicity.

    Human volume depletion/dehydration → Human serum lithium concentration source_derived_draftungraded
    Experimental context and source evidence

    evidence_access

    Official prescribing information

    experimental_model

    Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

    limitations

    Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

    nutrient_topic

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

    plain_language

    Fluid loss can amplify exposure.

    primary_references

    Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

    Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 568–574

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

    ## lithium-dehydration Fluid loss can amplify exposure. Dehydration can promote lithium retention and toxicity. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

    Complete structured claim and evidence

21. The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis.

    Mn2+ → Human arginase 2 / ARG2 source_derived_draftungraded
    Experimental context and source evidence

    experimental_model

    Crystal structure of active truncated human ARG2 with transition-state analogue

    exposure

    Boronic-acid inhibitor complex; 2.7-A structure

    limitations

    Structural consistency with the proposed mechanism; truncated active recombinant human ARG2 with inhibitor, not direct dietary manganese perturbation.

    nutrient_topic

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

    organism

    Homo sapiens protein

    plain_language

    Two manganese ions help ARG2 activate the water-derived attacking group.

    primary_references

    [mn-enz-12859189] Human arginase II: crystal structure and physiological role in male and female sexual arousal. (2003). https://pubmed.ncbi.nlm.nih.gov/12859189/ DOI: 10.1021/bi034340j

    tissue_or_cell_type

    Purified ARG2

    Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 584–594

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure of active truncated human ARG2 with transition-state analogue · source_derived_draft · unverified_draft

    ### mn-enz-arg2-metal-hydroxide The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two manganese ions help ARG2 activate the water-derived attacking group. organism: Homo sapiens protein tissue_or_cell_type: Purified ARG2 experimental_model: Crystal structure of active truncated human ARG2 with transition-state analogue limitations: Structural consistency with the proposed mechanism; truncated active recombinant human ARG2 with inhibitor, not direct dietary manganese perturbation. exposure: Boronic-acid inhibitor complex; 2.7-A structure [mn-enz-12859189] Human arginase II: crystal structure and physiological role in male and female sexual arousal. (2003). https://pubmed.ncbi.nlm.nih.gov/12859189/ DOI: 10.1021/bi034340j

    Complete structured claim and evidence

22. The human SOD2 active-site manganese is coordinated by His26, His74, His163, Asp159 and a water/hydroxide ligand in the structural model.

    Mn2+ → Human mitochondrial manganese superoxide dismutase / SOD2 source_derived_draftungraded
    Experimental context and source evidence

    experimental_model

    Redox-controlled neutron structures of human SOD2

    exposure

    Redox-controlled Mn(III) and Mn(II) crystals

    limitations

    Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.

    nutrient_topic

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

    organism

    Homo sapiens

    plain_language

    A defined protein pocket holds manganese for SOD2 chemistry.

    primary_references

    [mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1

    tissue_or_cell_type

    Purified enzyme; mitochondrial-matrix protein

    Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 434–444

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Redox-controlled neutron structures of human SOD2 · source_derived_draft · unverified_draft

    ### mn-enz-sod2-coordination The human SOD2 active-site manganese is coordinated by His26, His74, His163, Asp159 and a water/hydroxide ligand in the structural model. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defined protein pocket holds manganese for SOD2 chemistry. organism: Homo sapiens tissue_or_cell_type: Purified enzyme; mitochondrial-matrix protein experimental_model: Redox-controlled neutron structures of human SOD2 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Redox-controlled Mn(III) and Mn(II) crystals [mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1

    Complete structured claim and evidence

23. The AASS reductase domain condenses lysine with 2-oxoglutarate using NADPH to form saccharopine.

    L-Lysine → Saccharopine source_derived_draftungraded
    Experimental context and source evidence

    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

    Complete structured claim and evidence

24. The AASS dehydrogenase domain oxidatively cleaves saccharopine, producing alpha-aminoadipate semialdehyde and glutamate with NAD+ reduction.

    Saccharopine → alpha-Aminoadipate semialdehyde source_derived_draftungraded
    Experimental context and source evidence

    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

    Complete structured claim and evidence

25. ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+.

    alpha-Aminoadipate semialdehyde → L-alpha-Aminoadipate source_derived_draftungraded
    Experimental context and source evidence

    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

    Complete structured claim and evidence

26. Human ALDH9A1 oxidizes trimethylaminobutyraldehyde to gamma-butyrobetaine using NAD+.

    4-Trimethylaminobutyraldehyde → gamma-Butyrobetaine source_derived_draftungraded
    Experimental context and source evidence

    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

    Complete structured claim and evidence

27. Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA.

    Crotonyl-CoA → (S)-3-Hydroxybutyryl-CoA source_derived_draftungraded
    Experimental context and source evidence

    experimental_model

    Crotonyl-CoA hydratase assays in control human fibroblasts

    limitations

    This shared short-chain reaction can process lysine-derived crotonyl-CoA, but the assay does not trace its carbon from lysine. Disease results are not used to label the control reaction as machinery impairment.

    organism

    Homo sapiens

    plain_language

    Water is added across the four-carbon intermediate's double bond.

    primary_references

    [ferdinandusse2015] Clinical and biochemical characterization of four patients with mutations in ECHS1 (2015). https://link.springer.com/article/10.1186/s13023-015-0290-1 DOI: 10.1186/s13023-015-0290-1

    tissue_or_cell_type

    Fibroblasts; mitochondrial enzyme

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 357–365

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crotonyl-CoA hydratase assays in control human fibroblasts · source_derived_draft · unverified_draft

    ### echs1-crotonyl-coa-hydration Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA. Plain language: Water is added across the four-carbon intermediate's double bond. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Fibroblasts; mitochondrial enzyme experimental_model: Crotonyl-CoA hydratase assays in control human fibroblasts limitations: This shared short-chain reaction can process lysine-derived crotonyl-CoA, but the assay does not trace its carbon from lysine. Disease results are not used to label the control reaction as machinery impairment. [ferdinandusse2015] Clinical and biochemical characterization of four patients with mutations in ECHS1 (2015). https://link.springer.com/article/10.1186/s13023-015-0290-1 DOI: 10.1186/s13023-015-0290-1

    Complete structured claim and evidence

28. Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide.

    Lysyl oxidase enzyme family → Collagen/elastin peptidyl lysine substrates source_derived_draftungraded
    Experimental context and source evidence

    experimental_model

    LOXL2 assay development and total-family activity detection in cultured cells and tissue.

    limitations

    Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury.

    organism

    Mammalian cells/tissues and recombinant LOXL2; see study methods

    plain_language

    An enzyme creates reactive attachment sites used in matrix cross-linking.

    primary_references

    [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/

    tissue_or_cell_type

    Not specified as a whole tissue; see experimental model.

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 467–475

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOXL2 assay development and total-family activity detection in cultured cells and tissue. · source_derived_draft · unverified_draft

    ### lox-peptidyl-lysine-oxidation Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide. Plain language: An enzyme creates reactive attachment sites used in matrix cross-linking. Condition category: normal organism: Mammalian cells/tissues and recombinant LOXL2; see study methods tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: LOXL2 assay development and total-family activity detection in cultured cells and tissue. limitations: Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury. [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/

    Complete structured claim and evidence

29. Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products.

    GPX1 → Hydrogen peroxide source_derived_draftliterature_reviewed:supported_interpretation
    Experimental context and source evidence

    experimental_model

    Animal selenium status and erythrocyte glutathione-peroxidase biochemistry.

    limitations

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

    organism

    Rat

    Selenium: literature corrections and mechanism additions · lines 954–963

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. · secondary_verified · secondary_verified

    ## gpx1-peroxide-reduction GPX1 uses glutathione to remove hydrogen peroxide. Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products. Experimental model: Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. Organism: Rat Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Selenium: biochemical role as a component of glutathione peroxidase](https://pubmed.ncbi.nlm.nih.gov/4686466/)

    Complete structured claim and evidence

30. Expressed human GPX2 exhibited glutathione-dependent hydrogen-peroxide reduction.

    GPX2 → Hydrogen peroxide source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence

    cell_type

    MCF-7 transfectants

    experimental_model

    GPX2 cDNA expression and enzyme assays

    limitations

    Expression model; not an intestinal clinical outcome.

    organism

    human

    Selenium: literature corrections and mechanism additions · lines 642–652

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · GPX2 cDNA expression and enzyme assays · secondary_verified · secondary_verified

    ## gpx2-reduces-peroxide GPX2 can remove peroxide using glutathione. Expressed human GPX2 exhibited glutathione-dependent hydrogen-peroxide reduction. Organism: human Cell type: MCF-7 transfectants Experimental model: GPX2 cDNA expression and enzyme assays Limitations: Expression model; not an intestinal clinical outcome. Primary reference: [Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI](https://pubmed.ncbi.nlm.nih.gov/8428933/)

    Complete structured claim and evidence

31. Purified human plasma glutathione peroxidase reduced hydrogen peroxide using glutathione.

    GPX3 → Hydrogen peroxide source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence

    cell_type

    plasma

    experimental_model

    Purified enzyme kinetics

    limitations

    Assay glutathione availability does not define every physiological electron donor.

    organism

    human

    Selenium: literature corrections and mechanism additions · lines 678–688

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

    ## gpx3-reduces-extracellular-peroxide GPX3 can remove peroxide outside cells. Purified human plasma glutathione peroxidase reduced hydrogen peroxide using glutathione. Organism: human Cell type: plasma Experimental model: Purified enzyme kinetics Limitations: Assay glutathione availability does not define every physiological electron donor. Primary reference: [Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase.](https://www.sciencedirect.com/science/article/pii/S0021925818453926)

    Complete structured claim and evidence

32. PRDX3 consumes hydrogen peroxide, forming water within the mitochondrial thioredoxin circuit.

    PRDX3 → Hydrogen peroxide source_derived_draftliterature_reviewed:supported_interpretation
    Experimental context and source evidence

    cell_type

    cardiac mitochondria

    experimental_model

    Peroxide and redox measurements

    limitations

    Other mitochondrial peroxide defenses also contribute.

    organism

    mouse and guinea pig

    Selenium: literature corrections and mechanism additions · lines 630–640

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Peroxide and redox measurements · secondary_verified · secondary_verified

    ## prdx3-reduces-mitochondrial-peroxide The relay ends in peroxide removal. PRDX3 consumes hydrogen peroxide, forming water within the mitochondrial thioredoxin circuit. Organism: mouse and guinea pig Cell type: cardiac mitochondria Experimental model: Peroxide and redox measurements Limitations: Other mitochondrial peroxide defenses also contribute. 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/)

    Complete structured claim and evidence

33. SELENOO catalyzes NAD+ hydrolysis to NMN and AMP.

    SELENOO → NAD+ source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence

    cell_type

    experimental cells

    experimental_model

    Biochemical and cellular assays

    limitations

    Recent 2026 finding; no dietary-dose inference.

    organism

    mammalian

    Selenium: literature corrections and mechanism additions · lines 438–448

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Biochemical and cellular assays · secondary_verified · secondary_verified

    ## selenoo-hydrolyzes-nad SELENOO can split NAD into two smaller molecules. SELENOO catalyzes NAD+ hydrolysis to NMN and AMP. Organism: mammalian Cell type: experimental cells Experimental model: Biochemical and cellular assays Limitations: Recent 2026 finding; no dietary-dose inference. Primary reference: [NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis](https://pubmed.ncbi.nlm.nih.gov/41806834/)

    Complete structured claim and evidence