Adenosine diphosphate

cross_nutrient

false

evidence_location

Full text Results; Figures 2-3, Table 3

experimental_model

Purified human proteins

exposure

ADP added to MMUT-bound cob(II)alamin under air

limitations

Structural/biochemical protection does not establish regulation by cellular energy charge.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

ADP helped preserve an inactive B12 cofactor for repair in the human-protein assay.

primary_references

[gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1398–1410

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

### adp-protects-mmut-cofactor-redox ADP binding protected cob(II)alamin on human MMUT from air oxidation by stabilizing a solvent-shielded conformation. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: ADP helped preserve an inactive B12 cofactor for repair in the human-protein assay. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Structural/biochemical protection does not establish regulation by cellular energy charge. exposure: ADP added to MMUT-bound cob(II)alamin under air cross_nutrient: false evidence_location: Full text Results; Figures 2-3, Table 3 [gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120

cross_nutrient

false

evidence_location

Full text Results; Figures 2-3, Table 3

experimental_model

Purified human proteins

exposure

Anaerobic cofactor-transfer assay with ADP

limitations

Transfer rate differs from oxidation protection; methylmalonyl-CoA reversed ADP inhibition in this assay.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

When oxidation was excluded, ADP slowed transfer of inactive B12 between the purified human proteins.

primary_references

[gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1412–1424

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

### adp-slows-mmut-cob-ii-offloading Under anaerobic conditions, ADP reduced the rate of cob(II)alamin transfer from human MMUT to MMAB in the MMAA repair system. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: When oxidation was excluded, ADP slowed transfer of inactive B12 between the purified human proteins. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Transfer rate differs from oxidation protection; methylmalonyl-CoA reversed ADP inhibition in this assay. exposure: Anaerobic cofactor-transfer assay with ADP cross_nutrient: false evidence_location: Full text Results; Figures 2-3, Table 3 [gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120

evidence_access

Primary abstract and full-text nucleotide analysis

experimental_model

Chicken muscle enzyme and nucleotide analysis.

limitations

Use ADP rather than the older inferred AMP assignment; no clinical magnesium-depletion threshold was measured.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

The synthesis reaction spends ATP and produces ADP.

primary_references

Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). · 2010 · https://pubmed.ncbi.nlm.nih.gov/20097752/ · DOI 10.1074/jbc.M109.095505

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 28–34

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Chicken muscle enzyme and nucleotide analysis. · source_derived_draft · unverified_draft

## carnosine-atp-product The synthesis reaction spends ATP and produces ADP. Purified chicken carnosine synthase formed ADP stoichiometrically during carnosine synthesis with MgATP. Model: Chicken muscle enzyme and nucleotide analysis. Limitations: Use ADP rather than the older inferred AMP assignment; no clinical magnesium-depletion threshold was measured. Evidence access: Primary abstract and full-text nucleotide analysis Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). · 2010 · https://pubmed.ncbi.nlm.nih.gov/20097752/ · DOI 10.1074/jbc.M109.095505

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets.

limitations

Computational inference, not a new binding measurement; more complex alternatives were not excluded.

nutrient_topic

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

organism

Mammalian datasets including Sus scrofa

plain_language

One model explains activation using two separate regulators.

primary_references

[qi-2011-ogdh] Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase (2011). https://link.springer.com/article/10.1186/1471-2091-12-53 DOI: 10.1186/1471-2091-12-53

tissue_or_cell_type

Published isolated-enzyme datasets

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 723–733

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets. · source_derived_draft · unverified_draft

### mg-ogdh-independent-adp-model A 2011 kinetic reanalysis favored independent Mg and ADP effects rather than requiring MgADP as the activating species. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: One model explains activation using two separate regulators. organism: Mammalian datasets including Sus scrofa tissue_or_cell_type: Published isolated-enzyme datasets experimental_model: Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets. limitations: Computational inference, not a new binding measurement; more complex alternatives were not excluded. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [qi-2011-ogdh] Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase (2011). https://link.springer.com/article/10.1186/1471-2091-12-53 DOI: 10.1186/1471-2091-12-53

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments.

limitations

Speciation-based interpretation; later modeling offered independent Mg/ADP effects.

nutrient_topic

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

organism

Sus scrofa

plain_language

The authors assigned enhanced activity to magnesium-bound ADP.

primary_references

[rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856

tissue_or_cell_type

Isolated heart enzyme; additional mitochondrial-extract source not resolved

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 699–709

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. · source_derived_draft · unverified_draft

### mg-ogdh-mgadp-interpretation The 2000 experiments interpreted MgADP as a more potent OGDHC activator than free ADP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The authors assigned enhanced activity to magnesium-bound ADP. organism: Sus scrofa tissue_or_cell_type: Isolated heart enzyme; additional mitochondrial-extract source not resolved experimental_model: Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. limitations: Speciation-based interpretation; later modeling offered independent Mg/ADP effects. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856

evidence_location

Indexed abstract and publisher abstract; human enzyme findings only

experimental_model

Purified recombinant human and E. coli pyridoxal kinases.

exposure

Purified-enzyme substrate kinetics.

limitations

Model-specific evidence; no dietary threshold or treatment benefit established.

nutrient_topic

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

organism

Homo sapiens

plain_language

PDXK adds phosphate to this B6 precursor.

primary_references

[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021

tissue_or_cell_type

Purified human enzyme

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 176–187

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

### b6-transport-pdxk-pm Purified recombinant human PDXK phosphorylated pyridoxamine to its corresponding 5-prime phosphate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PDXK adds phosphate to this B6 precursor. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Model-specific evidence; no dietary threshold or treatment benefit established. exposure: Purified-enzyme substrate kinetics. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021

evidence_location

Indexed abstract and publisher abstract; human enzyme findings only

experimental_model

Purified recombinant human and E. coli pyridoxal kinases.

exposure

Purified-enzyme substrate kinetics.

limitations

Model-specific evidence; no dietary threshold or treatment benefit established.

nutrient_topic

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

organism

Homo sapiens

plain_language

PDXK adds phosphate to this B6 precursor.

primary_references

[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021

tissue_or_cell_type

Purified human enzyme

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 163–174

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

### b6-transport-pdxk-pn Purified recombinant human PDXK phosphorylated pyridoxine to its corresponding 5-prime phosphate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: PDXK adds phosphate to this B6 precursor. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Model-specific evidence; no dietary threshold or treatment benefit established. exposure: Purified-enzyme substrate kinetics. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021

evidence_span

{"source_cache": "artifacts/choline-research/25515750.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb", "start_char": 0, "end_char": 1321, "text_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb"}

experimental_model

Human choline kinase alpha1 and pathogen-enzyme biochemical comparison

exposure

ATP-dependent choline phosphorylation in magnesium-containing assays

limitations

The shared enzyme requirement is not a clinical magnesium threshold or proof of a general supplement rescue.

nutrient_topic

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

organism

Human alpha1 isoform; pathogen comparators remain separate

plain_language

Choline enters membrane synthesis through an ATP-powered phosphorylation step.

primary_references

[choline-p25515750] Choline kinase active site provides features for designing versatile inhibitors. (2014). https://pubmed.ncbi.nlm.nih.gov/25515750/ DOI: 10.2174/1568026614666141216093337

tissue_or_cell_type

Purified choline kinase active site

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 698–709

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human choline kinase alpha1 and pathogen-enzyme biochemical comparison · source_derived_draft · unverified_draft

### choline-chka-phosphocholine Human choline kinase alpha1 catalyzes ATP-dependent phosphorylation of choline, producing phosphocholine and ADP in magnesium-containing conditions. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline enters membrane synthesis through an ATP-powered phosphorylation step. organism: Human alpha1 isoform; pathogen comparators remain separate tissue_or_cell_type: Purified choline kinase active site experimental_model: Human choline kinase alpha1 and pathogen-enzyme biochemical comparison limitations: The shared enzyme requirement is not a clinical magnesium threshold or proof of a general supplement rescue. exposure: ATP-dependent choline phosphorylation in magnesium-containing assays evidence_span: {"source_cache": "artifacts/choline-research/25515750.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb", "start_char": 0, "end_char": 1321, "text_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb"} [choline-p25515750] Choline kinase active site provides features for designing versatile inhibitors. (2014). https://pubmed.ncbi.nlm.nih.gov/25515750/ DOI: 10.2174/1568026614666141216093337

evidence_access

Primary abstract

experimental_model

Rat liver F1 crystallography.

limitations

A captured structure is not proof that a given oral dose suppresses mitochondrial ATP production.

nutrient_topic

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

plain_language

Another ATP-handling enzyme can bind the phosphate analogue.

primary_references

Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16531409/ · DOI 10.1074/jbc.M513369200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 262–268

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver F1 crystallography. · source_derived_draft · unverified_draft

## vanadium-f1-transition Another ATP-handling enzyme can bind the phosphate analogue. Vanadate crystallization of rat-liver F1 ATP synthase captured an ADP–vanadate–Mg transition-like state with remodeling of the catalytic P-loop region. Model: Rat liver F1 crystallography. Limitations: A captured structure is not proof that a given oral dose suppresses mitochondrial ATP production. Evidence access: Primary abstract Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16531409/ · DOI 10.1074/jbc.M513369200

evidence_span

{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}

experimental_model

X-ray structure of a creatine kinase transition-state analogue complex

exposure

ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution

limitations

Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.

nutrient_topic

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

organism

Torpedo californica enzyme

plain_language

Magnesium helps position the phosphate-transfer chemistry; creatine is only one component of that reaction.

primary_references

[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

tissue_or_cell_type

Purified creatine kinase

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 347–358

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft

### creatine-ck-magnesium-complex Magnesium in the transition-state analogue complex coordinated ADP, nitrate and water ligands at the creatine kinase active site. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps position the phosphate-transfer chemistry; creatine is only one component of that reaction. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

evidence_span

{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}

experimental_model

X-ray structure of a creatine kinase transition-state analogue complex

exposure

ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution

limitations

Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.

nutrient_topic

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

organism

Torpedo californica enzyme

plain_language

Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated.

primary_references

[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

tissue_or_cell_type

Purified creatine kinase

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 334–345

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft

### creatine-ck-reversible-phosphate Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

evidence_span

{"source_cache": "artifacts/creatine-research/8692275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6", "start_char": 0, "end_char": 1125, "text_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6"}

experimental_model

Mitochondrial creatine kinase crystal structure

exposure

Octamer architecture and electrostatic surface analysis

limitations

The abstract does not specify the organism; no human-specific structural assignment is made. Membrane binding interpretation accompanies structural data.

nutrient_topic

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

organism

Mitochondrial creatine kinase preparation in the primary study

plain_language

Mitochondrial creatine kinase can load the phosphate carrier near the site of ATP production.

primary_references

[creatine-p8692275] Structure of mitochondrial creatine kinase. (1996). https://pubmed.ncbi.nlm.nih.gov/8692275/ DOI: 10.1038/381341a0

tissue_or_cell_type

Purified protein; mitochondrial membrane interface interpretation

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 360–371

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

### creatine-mitochondrial-ck-organization The mitochondrial creatine kinase structure supported an octameric enzyme positioned to convert mitochondrially generated ATP into phosphocreatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial creatine kinase can load the phosphate carrier near the site of ATP production. organism: Mitochondrial creatine kinase preparation in the primary study tissue_or_cell_type: Purified protein; mitochondrial membrane interface interpretation experimental_model: Mitochondrial creatine kinase crystal structure limitations: The abstract does not specify the organism; no human-specific structural assignment is made. Membrane binding interpretation accompanies structural data. exposure: Octamer architecture and electrostatic surface analysis evidence_span: {"source_cache": "artifacts/creatine-research/8692275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6", "start_char": 0, "end_char": 1125, "text_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6"} [creatine-p8692275] Structure of mitochondrial creatine kinase. (1996). https://pubmed.ncbi.nlm.nih.gov/8692275/ DOI: 10.1038/381341a0

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

State 4 respiration did not change

experimental_model

Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates.

exposure

Low-thiamine diet plus pyrithiamine in rats

limitations

Does not demonstrate that thiamine directly forms part of the respiratory chain or that all electron-transport activity fails.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

The mitochondrial deficit depended on both substrate and respiratory state.

primary_references

[parker-1984-brain-mitochondria] Brain mitochondrial metabolism in experimental thiamine deficiency (1984). https://pubmed.ncbi.nlm.nih.gov/6493495/ DOI: 10.1212/wnl.34.11.1477

tissue_or_cell_type

Isolated brain mitochondria

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1127–1139

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates. · source_derived_draft · unverified_draft

### thiamine-def-brain-state3-respiration Brain mitochondrial state 3 respiration fell with pyruvate/malate, 2-oxoglutarate or glutamate as substrates; state 4 respiration did not change. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial deficit depended on both substrate and respiratory state. organism: Rattus norvegicus tissue_or_cell_type: Isolated brain mitochondria experimental_model: Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates. limitations: Does not demonstrate that thiamine directly forms part of the respiratory chain or that all electron-transport activity fails. evidence_location: Abstract evidence_span: State 4 respiration did not change exposure: Low-thiamine diet plus pyrithiamine in rats [parker-1984-brain-mitochondria] Brain mitochondrial metabolism in experimental thiamine deficiency (1984). https://pubmed.ncbi.nlm.nih.gov/6493495/ DOI: 10.1212/wnl.34.11.1477

evidence_access

Primary abstract

experimental_model

Isolated bovine heart F1 structures and inhibition study.

limitations

The proposed block of rotation explains inhibition; the structure does not establish human tissue ATP loss after oral intake.

nutrient_topic

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

plain_language

Binding can obstruct the rotary machinery for energy conversion.

primary_references

Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17698806/ · DOI 10.1073/pnas.0706290104

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 142–148

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated bovine heart F1 structures and inhibition study. · source_derived_draft · unverified_draft

## resveratrol-f1-binding Binding can obstruct the rotary machinery for energy conversion. The bovine F1-ATPase crystal structure placed resveratrol in a pocket between the gamma tip and beta-TP subunit at the rotary bearing. Model: Isolated bovine heart F1 structures and inhibition study. Limitations: The proposed block of rotation explains inhibition; the structure does not establish human tissue ATP loss after oral intake. Evidence access: Primary abstract Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17698806/ · DOI 10.1073/pnas.0706290104

evidence_location

Abstract and product-bound structure

experimental_model

Human RFK structural and catalytic mechanism study

exposure

Purified RFK with flavin and adenine nucleotide ligands.

limitations

Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.

nutrient_topic

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

organism

Homo sapiens

plain_language

RFK performs the first activation step from riboflavin to FMN.

primary_references

[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t

tissue_or_cell_type

Purified protein

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft

### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t

evidence_access

Primary abstract

experimental_model

Mouse islet nucleotide assays; the same paper reports reduced KATP conductance.

limitations

The causal chain from nucleotide change to conductance was proposed rather than isolated by every possible intervention.

nutrient_topic

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

plain_language

Energy state may connect a glycoside response to potassium-channel closure.

primary_references

Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 242–248

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islet nucleotide assays; the same paper reports reduced KATP conductance. · source_derived_draft · unverified_draft

## stevia-reba-atp Energy state may connect a glycoside response to potassium-channel closure. Rebaudioside A at 1 nM increased the ATP/ADP ratio at 16.7 mM glucose while not changing measured cAMP. Model: Mouse islet nucleotide assays; the same paper reports reduced KATP conductance. Limitations: The causal chain from nucleotide change to conductance was proposed rather than isolated by every possible intervention. Evidence access: Primary abstract Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

evidence_access

Primary abstract

experimental_model

Alpha-ketoglutarate- or succinate-supported respiration.

limitations

Suggests effects on energy transduction; not direct structural proof of ATP-synthase binding.

nutrient_topic

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

plain_language

Energy conversion can be impaired at experimental exposures.

primary_references

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

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 336–342

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Alpha-ketoglutarate- or succinate-supported respiration. · source_derived_draft · unverified_draft

## fisetin-rat-respiration Energy conversion can be impaired at experimental exposures. Fisetin reduced respiratory control and ADP/O ratios and inhibited ADP-stimulated respiration in isolated rat mitochondria. Model: Alpha-ketoglutarate- or succinate-supported respiration. Limitations: Suggests effects on energy transduction; not direct structural proof of ATP-synthase binding. Evidence access: Primary abstract Prooxidant activity of fisetin: effects on energy metabolism in the rat liver. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20957679/ · DOI 10.1002/jbt.20367

dose

Bromelain 0.4 U/mL

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human normal and hypercoagulable blood samples

limitations

Neither oral nor intravenous exposure was tested; the small mouse experiment showed a nonsignificant trend toward hypercoagulability after intraperitoneal dosing.

nutrient_topic

Bromelain chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Bromelain

organism

Human normal and hypercoagulable blood samples

plain_language

Adding bromelain ex vivo reduced coagulability, prolonged PT/APTT, and reduced ADP-induced platelet aggregation in human blood samples.

primary_references

Bromelain has paradoxical effects on blood coagulability: a study using thromboelastography. (2016). https://pubmed.ncbi.nlm.nih.gov/25517253/ DOI: 10.1097/MBC.0000000000000244

route

Ex vivo addition

tissue

Thromboelastography, PT, APTT and platelet aggregation

Bromelain: mechanism of action and interactions (2026-09-20) · lines 110–119

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human normal and hypercoagulable blood samples · source_derived_draft · unverified_draft

## bromelain-exvivo-coagulation Adding bromelain ex vivo reduced coagulability, prolonged PT/APTT, and reduced ADP-induced platelet aggregation in human blood samples. Model/species: Human normal and hypercoagulable blood samples Tissue/system: Thromboelastography, PT, APTT and platelet aggregation Exposure: Bromelain 0.4 U/mL Route: Ex vivo addition Duration: Acute Limits: Neither oral nor intravenous exposure was tested; the small mouse experiment showed a nonsignificant trend toward hypercoagulability after intraperitoneal dosing. Primary reference: Bromelain has paradoxical effects on blood coagulability: a study using thromboelastography. (2016). https://pubmed.ncbi.nlm.nih.gov/25517253/ DOI: 10.1097/MBC.0000000000000244 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

{"source_cache": "artifacts/cold-research/26496606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7", "start_char": 0, "end_char": 1097, "text_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7"}

experimental_model

Quantitative mitochondrial proteomics of brown and beige fat with pharmacological creatine reduction

exposure

Cold exposure, beta-3 agonist administration, and creatine depletion

limitations

Identifies a UCP1-independent route. Pharmacological creatine reduction is a blunt tool, and the compensatory induction in UCP1-deficient mice is an expression finding.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

A second heat route runs a creatine cycle that burns energy on purpose.

primary_references

[cold-p26496606] A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. (2015). https://pubmed.ncbi.nlm.nih.gov/26496606/ DOI: 10.1016/j.cell.2015.09.035

tissue_or_cell_type

Beige and brown adipose tissue

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 442–453

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative mitochondrial proteomics of brown and beige fat with pharmacological creatine reduction · source_derived_draft · unverified_draft

### cold-creatine-cycle Creatine enhanced respiration in beige-fat mitochondria when ADP was limiting, and cold exposure stimulated mitochondrial creatine kinase activity and induced coordinated expression of creatine metabolism genes in murine beige fat. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: A second heat route runs a creatine cycle that burns energy on purpose. organism: Mouse tissue_or_cell_type: Beige and brown adipose tissue experimental_model: Quantitative mitochondrial proteomics of brown and beige fat with pharmacological creatine reduction limitations: Identifies a UCP1-independent route. Pharmacological creatine reduction is a blunt tool, and the compensatory induction in UCP1-deficient mice is an expression finding. exposure: Cold exposure, beta-3 agonist administration, and creatine depletion evidence_span: {"source_cache": "artifacts/cold-research/26496606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7", "start_char": 0, "end_char": 1097, "text_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7"} [cold-p26496606] A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. (2015). https://pubmed.ncbi.nlm.nih.gov/26496606/ DOI: 10.1016/j.cell.2015.09.035

experimental_model

Human GLUL ligand-complex crystal structures; canine apoenzyme comparison

exposure

ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes

limitations

Crystallographic Mn binding does not establish exclusive Mn dependence or endogenous human brain metal occupancy.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

Human GLUL can bind manganese in the reported structural complexes.

primary_references

[mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029

tissue_or_cell_type

Purified GLUL

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 608–618

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft

### mn-enz-glul-mn-crystals Human GLUL crystal structures contained Mn with ADP/phosphate or ADP/phosphorylated methionine-sulfoximine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human GLUL can bind manganese in the reported structural complexes. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Crystallographic Mn binding does not establish exclusive Mn dependence or endogenous human brain metal occupancy. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029

experimental_model

Human GLUL ligand-complex crystal structures; canine apoenzyme comparison

exposure

ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes

limitations

Reaction identity does not determine the predominant metal in living human brain.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

GLUL combines glutamate and ammonia using ATP.

primary_references

[mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029

tissue_or_cell_type

Purified GLUL

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 596–606

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft

### mn-enz-glul-reaction Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: GLUL combines glutamate and ammonia using ATP. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Reaction identity does not determine the predominant metal in living human brain. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029

dose

Fructose substrate and ATP-dependent enzyme characterization; exact concentrations not in abstract

duration

Assay duration not recovered

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Ketohexokinase purified from human liver

exposure_scope

Human component biochemistry

limitations

Isoform unresolved; enzyme chemistry does not quantify whole-body flux after ordinary HFCS intake. Only abstract/metadata recovered for this scanned article.

nutrient_topic

HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished. · High-Fructose Corn Syrup / HFCS

organism

Ketohexokinase purified from human liver

plain_language

Purified human liver ketohexokinase catalyzed the ATP-dependent phosphorylation of fructose.

primary_references

The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol. (1985). https://pubmed.ncbi.nlm.nih.gov/2996495/ DOI: 10.1042/bj2300053

route

In vitro enzyme/substrate incubation

tissue

Cell-free enzyme kinetics

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 101–111

Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Ketohexokinase purified from human liver · source_derived_draft · unverified_draft

## hfcs-khk-phosphorylation Purified human liver ketohexokinase catalyzed the ATP-dependent phosphorylation of fructose. Model/species: Ketohexokinase purified from human liver Tissue: Cell-free enzyme kinetics Exposure: Fructose substrate and ATP-dependent enzyme characterization; exact concentrations not in abstract Route: In vitro enzyme/substrate incubation Duration: Assay duration not recovered Exposure scope: Human component biochemistry Limits: Isoform unresolved; enzyme chemistry does not quantify whole-body flux after ordinary HFCS intake. Only abstract/metadata recovered for this scanned article. Reference: The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol. (1985). https://pubmed.ncbi.nlm.nih.gov/2996495/ DOI: 10.1042/bj2300053 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/24953906.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717", "start_char": 0, "end_char": 1870, "text_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717"}

experimental_model

In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control

exposure

Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists

limitations

The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

Capsaicin blocks clumping triggered two ways; dihydrocapsaicin blocks only one of them.

primary_references

[dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

tissue_or_cell_type

Platelets

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 153–164

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control · source_derived_draft · unverified_draft

### dhc-platelet-divergence Capsaicin, N-oleoyldopamine and N-arachidonoyl-dopamine inhibited ADP-induced platelet aggregation in a concentration-dependent manner, while arachidonic-acid-induced aggregation was inhibited by capsaicin, dihydrocapsaicin and N-arachidonoyl-dopamine but not by N-oleoyldopamine, and collagen-induced aggregation was inhibited only by the endogenous vanilloids and not by capsaicin or dihydrocapsaicin. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Capsaicin blocks clumping triggered two ways; dihydrocapsaicin blocks only one of them. organism: Human tissue_or_cell_type: Platelets experimental_model: In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control limitations: The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included. exposure: Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24953906.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717", "start_char": 0, "end_char": 1870, "text_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717"} [dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

dose

Purified hericenone B with multiple agonists

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Washed rabbit and human platelets

limitations

The proposed integrin-alpha2/beta1-to-arachidonate step was not a human oral antithrombotic trial.

nutrient_topic

Hericenones & Erinacines chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Hericenones and erinacines

organism

Washed rabbit and human platelets

plain_language

Hericenone B inhibited collagen-induced aggregation in washed rabbit and human platelets but did not inhibit aggregation induced by U46619, ADP, thrombin, adrenaline, arachidonic acid or convulxin.

primary_references

Inhibitory effect of hericenone B from Hericium erinaceus on collagen-induced platelet aggregation. (2010). https://pubmed.ncbi.nlm.nih.gov/20637576/ DOI: 10.1016/j.phymed.2010.05.004

route

In vitro

tissue

Agonist-specific platelet aggregation

Hericenones & Erinacines: mechanism of action and interactions (2026-09-20) · lines 55–64

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Washed rabbit and human platelets · source_derived_draft · unverified_draft

## hericenones-erinacines-hericenone-b-platelets Hericenone B inhibited collagen-induced aggregation in washed rabbit and human platelets but did not inhibit aggregation induced by U46619, ADP, thrombin, adrenaline, arachidonic acid or convulxin. Model/species: Washed rabbit and human platelets Tissue/system: Agonist-specific platelet aggregation Exposure: Purified hericenone B with multiple agonists Route: In vitro Duration: Acute Limits: The proposed integrin-alpha2/beta1-to-arachidonate step was not a human oral antithrombotic trial. Primary reference: Inhibitory effect of hericenone B from Hericium erinaceus on collagen-induced platelet aggregation. (2010). https://pubmed.ncbi.nlm.nih.gov/20637576/ DOI: 10.1016/j.phymed.2010.05.004 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

cross_nutrient

Magnesium and ATP support folate interconversion.

experimental_model

Purified liver enzyme

exposure

Controlled enzyme assay with ATP and magnesium.

limitations

Cofactor dependence does not establish a dietary magnesium threshold.

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

ATP supplies energy for this magnesium-dependent folate conversion.

primary_references

[bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5

tissue_or_cell_type

Liver-derived, cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1255–1266

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

### mthfs-atp-magnesium-dependence The purified human liver MTHFS reaction requires ATP and Mg2+ and is an ADP-forming cyclo-ligase reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP supplies energy for this magnesium-dependent folate conversion. organism: Homo sapiens tissue_or_cell_type: Liver-derived, cell-free experimental_model: Purified liver enzyme limitations: Cofactor dependence does not establish a dietary magnesium threshold. exposure: Controlled enzyme assay with ATP and magnesium. cross_nutrient: Magnesium and ATP support folate interconversion. [bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5

cross_nutrient

false

experimental_model

Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution

exposure

DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis.

limitations

Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured.

nutrient_topic

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

organism

Homo sapiens

plain_language

The final COASY reaction completes CoA.

primary_references

[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 587–598

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

### b5-bio-coasy-phosphorylation Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The final COASY reaction completes CoA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured. exposure: DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

cross_nutrient

true

experimental_model

Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments

exposure

In-vitro biochemical exposure; concentrations not extracted.

limitations

Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here.

nutrient_topic

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

organism

Homo sapiens

plain_language

PANK3 starts vitamin B5 activation by adding phosphate.

primary_references

[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 483–494

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft

### b5-bio-pank3-phosphorylation Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PANK3 starts vitamin B5 activation by adding phosphate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: true [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061

cross_nutrient

false

experimental_model

Human SLC25A42 expressed in E. coli, purified and reconstituted into phospholipid vesicles, plus mitochondrial targeting experiments

exposure

Purified transporter proteoliposomes; substrate concentrations not extracted.

limitations

The experiment established exchange, not uniport. The proposed physiological import direction depends on metabolite gradients; the study does not establish that SLC25A42 is the sole importer.

nutrient_topic

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

organism

Homo sapiens

plain_language

Cells need transport machinery to supply the mitochondrial CoA compartment.

primary_references

[b5-bio-slc25a42] A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3',5'-diphosphate in human mitochondria. (2009). https://pubmed.ncbi.nlm.nih.gov/19429682/ DOI: 10.1074/jbc.m109.014118

tissue_or_cell_type

Reconstituted phospholipid vesicles and mitochondrial-targeting experiments

transport_effect

raises Counter-exchange transport that the record describes as a route for mitochondrial CoA import.

transport_pool

the mitochondrial matrix Counter-exchange transport that the record describes as a route for mitochondrial CoA import.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 704–715

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC25A42 expressed in E. coli, purified and reconstituted into phospholipid vesicles, plus mitochondrial targeting experiments · source_derived_draft · unverified_draft

### b5-bio-slc25a42-exchange Reconstituted human SLC25A42 transported CoA by counter-exchange and targeted mitochondria, supporting a route for mitochondrial CoA import. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells need transport machinery to supply the mitochondrial CoA compartment. organism: Homo sapiens tissue_or_cell_type: Reconstituted phospholipid vesicles and mitochondrial-targeting experiments experimental_model: Human SLC25A42 expressed in E. coli, purified and reconstituted into phospholipid vesicles, plus mitochondrial targeting experiments limitations: The experiment established exchange, not uniport. The proposed physiological import direction depends on metabolite gradients; the study does not establish that SLC25A42 is the sole importer. exposure: Purified transporter proteoliposomes; substrate concentrations not extracted. cross_nutrient: false [b5-bio-slc25a42] A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3',5'-diphosphate in human mitochondria. (2009). https://pubmed.ncbi.nlm.nih.gov/19429682/ DOI: 10.1074/jbc.m109.014118

evidence_span

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experimental_model

Freeze-clamped liver metabolite measurement in starved rats after ethanol

exposure

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

limitations

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

nutrient_topic

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

organism

Rat

plain_language

Two other energy ratios move as well, and they recover on different timescales.

primary_references

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

tissue_or_cell_type

Liver

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 111–122

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

### alcohol-nadp-and-phosphorylation The free cytosolic NADP+/NADPH ratio fell immediately and returned nearly to control by 15 minutes, while the cytosolic ATP/ADP phosphate ratio was elevated at 15 minutes in starved rats. Condition category: normal nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: Two other energy ratios move as well, and they recover on different timescales. organism: Rat tissue_or_cell_type: Liver experimental_model: Freeze-clamped liver metabolite measurement in starved rats after ethanol limitations: The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state. exposure: Single ethanol dose, sampled over 30 minutes in fed and starved animals evidence_span: {"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"} [alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387