Coenzyme A

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC culture and exogenous CoA treatment.

limitations

Cell-culture rescue does not establish oral CoA absorption, intact cellular uptake in vivo or clinical efficacy.

nutrient_topic

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

plain_language

Restoring a downstream metabolite bypassed part of an upstream block in culture.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 220–226

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture and exogenous CoA treatment. · source_derived_draft · unverified_draft

## l-cysteine-pdac-coa-rescue Restoring a downstream metabolite bypassed part of an upstream block in culture. Adding CoA prevented ferroptosis induced by imidazole ketone erastin in the reported PDAC cell experiments. Model: Human PDAC culture and exogenous CoA treatment. Limitations: Cell-culture rescue does not establish oral CoA absorption, intact cellular uptake in vivo or clinical efficacy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

cross_nutrient

false

evidence_location

Abstract, substrate-specificity result

experimental_model

Recombinant human phosphopantetheinyl transferase and FASN ACP substrate

exposure

In-vitro enzymatic transfer from CoA; no dietary intervention.

limitations

Abstract-limited extraction; catalytic activation is distinguished from measuring whole-cell fatty-acid flux. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

CoA supplies the movable chemical arm used by the fatty-acid synthase carrier domain.

primary_references

[b5-met-joshi2003] Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity. (2003). https://pubmed.ncbi.nlm.nih.gov/12815048/ DOI: 10.1074/jbc.m305459200

tissue_or_cell_type

Cytosolic FASN ACP domain

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 795–807

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human phosphopantetheinyl transferase and FASN ACP substrate · source_derived_draft · unverified_draft

### b5-met-aasdhppt-fasn Human AASDHPPT transfers the 4′-phosphopantetheine moiety of CoA to a conserved serine in the human FASN acyl-carrier domain. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoA supplies the movable chemical arm used by the fatty-acid synthase carrier domain. organism: Homo sapiens tissue_or_cell_type: Cytosolic FASN ACP domain experimental_model: Recombinant human phosphopantetheinyl transferase and FASN ACP substrate limitations: Abstract-limited extraction; catalytic activation is distinguished from measuring whole-cell fatty-acid flux. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: In-vitro enzymatic transfer from CoA; no dietary intervention. cross_nutrient: false evidence_location: Abstract, substrate-specificity result [b5-met-joshi2003] Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity. (2003). https://pubmed.ncbi.nlm.nih.gov/12815048/ DOI: 10.1074/jbc.m305459200

cross_nutrient

false

evidence_location

Abstract, substrate-specificity result

experimental_model

Recombinant human transferase and mitochondrial ACP substrate

exposure

Enzymatic transfer from CoA; no dietary intervention.

limitations

The experiment establishes substrate competence, not the in-vivo location of the transfer reaction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

The mitochondrial carrier protein also needs a chemical arm derived from CoA.

primary_references

[b5-met-joshi2003] Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity. (2003). https://pubmed.ncbi.nlm.nih.gov/12815048/ DOI: 10.1074/jbc.m305459200

tissue_or_cell_type

Mitochondrial ACP substrate; in-vitro reaction

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 809–821

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

### b5-met-aasdhppt-mtacp Human AASDHPPT transfers the CoA-derived 4′-phosphopantetheine group to a conserved serine in human mitochondrial ACP. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial carrier protein also needs a chemical arm derived from CoA. organism: Homo sapiens tissue_or_cell_type: Mitochondrial ACP substrate; in-vitro reaction experimental_model: Recombinant human transferase and mitochondrial ACP substrate limitations: The experiment establishes substrate competence, not the in-vivo location of the transfer reaction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Enzymatic transfer from CoA; no dietary intervention. cross_nutrient: false evidence_location: Abstract, substrate-specificity result [b5-met-joshi2003] Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity. (2003). https://pubmed.ncbi.nlm.nih.gov/12815048/ DOI: 10.1074/jbc.m305459200

cross_nutrient

Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested.

evidence

[{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Reconstituted human enzyme pathway.

limitations

Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

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

organism

Homo sapiens

plain_language

Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step.

primary_references

[daugherty-2002-coa] 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 enzymes

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–743

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

### b1-coa-b5-downstream-biosynthesis Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzymes experimental_model: Reconstituted human enzyme pathway. limitations: Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction. evidence: [{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested. nutrient: Thiamine (vitamin B1) [daugherty-2002-coa] 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

B1-dependent E1 and B5-derived CoA participate in different sequential steps.

evidence

[{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human DLAT cryo-EM; bacterial ligand poses used for modeling.

limitations

Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

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

organism

Homo sapiens

plain_language

After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier.

primary_references

[jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357

tissue_or_cell_type

Purified catalytic core

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 690–702

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLAT cryo-EM; bacterial ligand poses used for modeling. · source_derived_draft · unverified_draft

### b1-pdh-dlat-coa-acetylation The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier. organism: Homo sapiens tissue_or_cell_type: Purified catalytic core experimental_model: Human DLAT cryo-EM; bacterial ligand poses used for modeling. limitations: Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment. evidence: [{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent E1 and B5-derived CoA participate in different sequential steps. nutrient: Thiamine (vitamin B1) [jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357

evidence_access

Primary full text

experimental_model

Human PDAC stable-isotope tracing.

limitations

No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues.

nutrient_topic

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

plain_language

Cysteine-derived material entered more than one protective metabolic pool.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC stable-isotope tracing. · source_derived_draft · unverified_draft

## l-cysteine-pdac-carbon-tracing Cysteine-derived material entered more than one protective metabolic pool. Carbon-13 cystine tracing showed labeling of glutathione and CoA over the experiment, including CoA labeling over 24 hours. Model: Human PDAC stable-isotope tracing. Limitations: No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC cultures with cystine-import inhibition and metabolomics.

limitations

Pantothenate accumulation is not proof of B5 toxicity or a clinical biomarker threshold.

nutrient_topic

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

plain_language

Vitamin B5 could accumulate while its downstream product fell because another substrate was missing.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures with cystine-import inhibition and metabolomics. · source_derived_draft · unverified_draft

## l-cysteine-pdac-coa-branch Vitamin B5 could accumulate while its downstream product fell because another substrate was missing. System xc− inhibition lowered CoA and increased upstream pantothenate in the tested pancreatic cancer cells. Model: Human PDAC cultures with cystine-import inhibition and metabolomics. Limitations: Pantothenate accumulation is not proof of B5 toxicity or a clinical biomarker threshold. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

cross_nutrient

false

experimental_model

Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments

exposure

Exogenous CoA; dose and assay-specific species not given in the abstract.

limitations

Abstract-level biochemical finding. ENPP isoform is unspecified here; this is not evidence for intact oral CoA delivery to the human brain.

nutrient_topic

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

organism

Eukaryotic experimental systems; abstract does not assign species to this reaction

plain_language

External CoA can be processed into a smaller CoA-building intermediate.

primary_references

[b5-bio-salvage2015] Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26322826/ DOI: 10.1038/nchembio.1906

tissue_or_cell_type

Extracellular biochemical/cell-culture environment

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 756–767

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments · source_derived_draft · unverified_draft

### b5-bio-extracellular-coa-processing The salvage study reported extracellular CoA hydrolysis by ectonucleotide pyrophosphatases to 4′-phosphopantetheine. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: External CoA can be processed into a smaller CoA-building intermediate. organism: Eukaryotic experimental systems; abstract does not assign species to this reaction tissue_or_cell_type: Extracellular biochemical/cell-culture environment experimental_model: Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments limitations: Abstract-level biochemical finding. ENPP isoform is unspecified here; this is not evidence for intact oral CoA delivery to the human brain. exposure: Exogenous CoA; dose and assay-specific species not given in the abstract. cross_nutrient: false [b5-bio-salvage2015] Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26322826/ DOI: 10.1038/nchembio.1906

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Full text lines 123–125, 173, 229; Fig. 4F; Extended Data Fig. 5G–H

experimental_model

Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts

exposure

Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice.

limitations

The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Human HCI002 grafts in Mus musculus hosts

plain_language

Direct B5 restriction lowered the tumor CoA pool in this particular graft model.

primary_references

[b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

tissue_or_cell_type

Orthotopic HCI002 tumor tissue

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1103–1115

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts · source_derived_draft · unverified_draft

### b5-met-diet-hci002-coa A pantothenate-free diet reduced free CoA measured in human HCI002 breast-cancer xenografts grown in mice. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct B5 restriction lowered the tumor CoA pool in this particular graft model. organism: Human HCI002 grafts in Mus musculus hosts tissue_or_cell_type: Orthotopic HCI002 tumor tissue experimental_model: Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts limitations: The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. cross_nutrient: false evidence_location: Full text lines 123–125, 173, 229; Fig. 4F; Extended Data Fig. 5G–H [b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Primary abstract, first four sentences

experimental_model

Rat pantothenate-deficient versus regular-diet feeding experiment

exposure

Pantothenic-acid-deficient diet; concentration and feeding duration unavailable in the abstract.

limitations

Whole-tissue CoA measurement does not establish unchanged subcellular pools or flux. Growth was impaired, so maintained CoA did not show nutritional adequacy. Different tissues/models from the tumor study do not constitute a same-context contradiction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Large drops in tissue B5 did not necessarily deplete the measured CoA pool in this rat experiment.

primary_references

[b5-met-rat1982] Coenzyme A metabolism in pantothenic acid-deficient rats. (1982). https://pubmed.ncbi.nlm.nih.gov/7086543/ DOI: 10.1093/jn/112.6.1144

tissue_or_cell_type

Heart, kidney, gastrocnemius, testes and liver

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1131–1143

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat pantothenate-deficient versus regular-diet feeding experiment · source_derived_draft · unverified_draft

### b5-met-rat-diet-coa-preserved Rats fed the pantothenate-deficient diet retained control-level tissue CoA despite more than 90% lower pantothenate in heart, kidney, gastrocnemius and testes and about 70% lower liver pantothenate. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Large drops in tissue B5 did not necessarily deplete the measured CoA pool in this rat experiment. organism: Rattus norvegicus tissue_or_cell_type: Heart, kidney, gastrocnemius, testes and liver experimental_model: Rat pantothenate-deficient versus regular-diet feeding experiment limitations: Whole-tissue CoA measurement does not establish unchanged subcellular pools or flux. Growth was impaired, so maintained CoA did not show nutritional adequacy. Different tissues/models from the tumor study do not constitute a same-context contradiction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Pantothenic-acid-deficient diet; concentration and feeding duration unavailable in the abstract. cross_nutrient: false evidence_location: Primary abstract, first four sentences [b5-met-rat1982] Coenzyme A metabolism in pantothenic acid-deficient rats. (1982). https://pubmed.ncbi.nlm.nih.gov/7086543/ DOI: 10.1093/jn/112.6.1144

evidence_span

{"source_cache": "artifacts/biotin-research/39383219.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5f7d3cd6a5865a03b8dc9c510f60249ee2c9f6516773780e5d7b4aef0a9b2db8", "start_char": 0, "end_char": 309, "text_sha256": "b094342ce091c8f919d065311ecd04ddd0c6b9b2824ba8adedd5768424a81a71"}

experimental_model

Cryo-EM of endogenous and recombinant human ACC1 filaments

exposure

Inactive substrate-containing and dephosphorylated/citrate-treated states

limitations

Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements.

nutrient_topic

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

organism

Homo sapiens

plain_language

ACC1 makes a building block used in fatty-acid synthesis.

primary_references

[b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

tissue_or_cell_type

Purified human ACC1

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 637–648

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of endogenous and recombinant human ACC1 filaments · source_derived_draft · unverified_draft

### b7-acc1-reaction Human ACC1 uses biotin-dependent carboxylation of acetyl-CoA to generate malonyl-CoA. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ACC1 makes a building block used in fatty-acid synthesis. organism: Homo sapiens tissue_or_cell_type: Purified human ACC1 experimental_model: Cryo-EM of endogenous and recombinant human ACC1 filaments limitations: Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements. exposure: Inactive substrate-containing and dephosphorylated/citrate-treated states evidence_span: {"source_cache": "artifacts/biotin-research/39383219.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5f7d3cd6a5865a03b8dc9c510f60249ee2c9f6516773780e5d7b4aef0a9b2db8", "start_char": 0, "end_char": 309, "text_sha256": "b094342ce091c8f919d065311ecd04ddd0c6b9b2824ba8adedd5768424a81a71"} [b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells

exposure

Separate and combined biotin and carnitine depletion

limitations

This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population.

nutrient_topic

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

organism

Homo sapiens

plain_language

Restoring carnitine exposed the unresolved biotin-related bottleneck.

primary_references

[b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343

tissue_or_cell_type

HepG2 hepatoma cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 975–986

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells · source_derived_draft · unverified_draft

### b7-carnitine-unmasking Carnitine repletion of doubly deficient HepG2 cells increased acetylcarnitine, propionylcarnitine and 3-hydroxyisovalerylcarnitine each by more than 50-fold. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring carnitine exposed the unresolved biotin-related bottleneck. organism: Homo sapiens tissue_or_cell_type: HepG2 hepatoma cells experimental_model: Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells limitations: This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population. exposure: Separate and combined biotin and carnitine depletion evidence_span: {"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"} [b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343

evidence_span

{"source_cache": "artifacts/biotin-research/21918059.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf", "start_char": 0, "end_char": 1723, "text_sha256": "5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf"}

experimental_model

Two human egg-white biotin-depletion cohorts with leucine challenges

exposure

28-day depletion in cohorts of 5 and 7 adults

limitations

Biomarker challenge study; the core MCC reaction is pathway background, not a new structural discovery.

nutrient_topic

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

organism

Homo sapiens

plain_language

Biotin helps process a carbon intermediate produced while breaking down leucine.

primary_references

[b7-p21918059] Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21918059/ DOI: 10.3945/jn.111.146126

tissue_or_cell_type

Leucine metabolism and urine

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 793–804

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human egg-white biotin-depletion cohorts with leucine challenges · source_derived_draft · unverified_draft

### b7-mcc-reaction MCC converts 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA in the leucine breakdown pathway using biotin. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin helps process a carbon intermediate produced while breaking down leucine. organism: Homo sapiens tissue_or_cell_type: Leucine metabolism and urine experimental_model: Two human egg-white biotin-depletion cohorts with leucine challenges limitations: Biomarker challenge study; the core MCC reaction is pathway background, not a new structural discovery. exposure: 28-day depletion in cohorts of 5 and 7 adults evidence_span: {"source_cache": "artifacts/biotin-research/21918059.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf", "start_char": 0, "end_char": 1723, "text_sha256": "5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf"} [b7-p21918059] Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21918059/ DOI: 10.3945/jn.111.146126

evidence_span

{"source_cache": "artifacts/biotin-research/36283412.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15", "start_char": 0, "end_char": 1060, "text_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15"}

experimental_model

Time-resolved cryo-EM and biochemical analysis of human PC

exposure

Pyruvate, ATP and acetyl-CoA catalytic conditions

limitations

Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue.

nutrient_topic

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

organism

Homo sapiens

plain_language

Acetyl-CoA helps put PC into its working shape.

primary_references

[b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033

tissue_or_cell_type

Purified human pyruvate carboxylase

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 559–570

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Time-resolved cryo-EM and biochemical analysis of human PC · source_derived_draft · unverified_draft

### b7-pc-acetylcoa Acetyl-CoA stabilized human PC in a catalytically competent conformation in time-resolved structural and biochemical experiments. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acetyl-CoA helps put PC into its working shape. organism: Homo sapiens tissue_or_cell_type: Purified human pyruvate carboxylase experimental_model: Time-resolved cryo-EM and biochemical analysis of human PC limitations: Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue. exposure: Pyruvate, ATP and acetyl-CoA catalytic conditions evidence_span: {"source_cache": "artifacts/biotin-research/36283412.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15", "start_char": 0, "end_char": 1060, "text_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15"} [b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033

evidence_access

Primary abstract

experimental_model

Purified human enzyme and potassium-bound structures.

limitations

Assay activation is not proof that extra potassium accelerates isoleucine breakdown in a potassium-replete person.

nutrient_topic

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

plain_language

Potassium changed the activity of an enzyme shared by isoleucine and ketone processing.

primary_references

Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 234–240

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme and potassium-bound structures. · source_derived_draft · unverified_draft

## isoleucine-acat1-potassium Potassium changed the activity of an enzyme shared by isoleucine and ketone processing. Increasing KCl from 0 to 40 mM increased purified human T2 turnover approximately threefold for both acetoacetyl-CoA and 2-methylacetoacetyl-CoA. Model: Purified human enzyme and potassium-bound structures. Limitations: Assay activation is not proof that extra potassium accelerates isoleucine breakdown in a potassium-replete person. Evidence access: Primary abstract Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

evidence_access

Primary abstract

experimental_model

Purified human T2 structural/kinetic study; established product chemistry.

limitations

ACAT1 here is acetyl-CoA acetyltransferase, not the cholesterol-esterifying SOAT1 enzyme sometimes called ACAT.

nutrient_topic

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

plain_language

One carbon skeleton feeds both an acetyl branch and a propionyl branch.

primary_references

Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human T2 structural/kinetic study; established product chemistry. · source_derived_draft · unverified_draft

## isoleucine-acat1-split One carbon skeleton feeds both an acetyl branch and a propionyl branch. Human mitochondrial ACAT1/T2 degraded 2-methylacetoacetyl-CoA by CoA-dependent thiolysis, yielding the isoleucine-branch acetyl-CoA and propionyl-CoA products. Model: Purified human T2 structural/kinetic study; established product chemistry. Limitations: ACAT1 here is acetyl-CoA acetyltransferase, not the cholesterol-esterifying SOAT1 enzyme sometimes called ACAT. Evidence access: Primary abstract Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

evidence_access

Primary full text, pathway background

experimental_model

Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper.

limitations

Cofactor and catalytic evidence is separately linked from existing ThDP/DLD records.

nutrient_topic

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

plain_language

A shared BCAA enzyme commits the carbon skeleton to further breakdown.

primary_references

Clinical and biochemical characterization of four patients with mutations in ECHS1. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26081110/ · DOI 10.1186/s13023-015-0290-1

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper. · source_derived_draft · unverified_draft

## isoleucine-bckdh-carbon-step A shared BCAA enzyme commits the carbon skeleton to further breakdown. The isoleucine pathway in the primary biochemical study places BCKDH-mediated oxidative decarboxylation of the branched ketoacid upstream of 2-methylbutyryl-CoA. Model: Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper. Limitations: Cofactor and catalytic evidence is separately linked from existing ThDP/DLD records. Evidence access: Primary full text, pathway background Clinical and biochemical characterization of four patients with mutations in ECHS1. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26081110/ · DOI 10.1186/s13023-015-0290-1

evidence_access

Primary abstract

experimental_model

Human colonic-cell metabolic experiments.

limitations

This is a multistep metabolic conversion; no single CoA ligase is assigned without direct evidence.

nutrient_topic

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

plain_language

The same carbon source supported both fuel use and adding acetyl marks.

primary_references

The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 182–188

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic-cell metabolic experiments. · source_derived_draft · unverified_draft

## butyrate-acetyl-coa The same carbon source supported both fuel use and adding acetyl marks. In the colonic-cell experiments, butyrate metabolism supplied acetyl-CoA for energy metabolism and histone acetyltransferase activity. Model: Human colonic-cell metabolic experiments. Limitations: This is a multistep metabolic conversion; no single CoA ligase is assigned without direct evidence. Evidence access: Primary abstract The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033

cross_nutrient

B6 and glycine support the porphyrin precursor pathway upstream of iron insertion.

experimental_model

Purified recombinant human ALAS2; crystallography and kinetics

limitations

Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction.

nutrient_topic

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

organism

Homo sapiens

plain_language

This B6-dependent step starts erythroid heme synthesis.

primary_references

[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 799–809

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft

### b6-met-alas2-ala Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step starts erythroid heme synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction. cross_nutrient: B6 and glycine support the porphyrin precursor pathway upstream of iron insertion. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x

evidence_access

Primary abstract

experimental_model

Human liver-derived cultured cells.

limitations

Cysteamine can arise through CoA breakdown; this experiment does not show that B5 supplementation raises taurine.

nutrient_topic

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

plain_language

Human-cell gene silencing supports the cysteamine pathway.

primary_references

Discovery and characterization of a second mammalian thiol dioxygenase, cysteamine dioxygenase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17581819/ · DOI 10.1074/jbc.M703089200

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 65–71

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human liver-derived cultured cells. · source_derived_draft · unverified_draft

## taurine-ado-human-knockdown Human-cell gene silencing supports the cysteamine pathway. RNA-mediated reduction of endogenous human ADO in HepG2/C3A cells decreased hypotaurine production from cysteamine. Model: Human liver-derived cultured cells. Limitations: Cysteamine can arise through CoA breakdown; this experiment does not show that B5 supplementation raises taurine. Evidence access: Primary abstract Discovery and characterization of a second mammalian thiol dioxygenase, cysteamine dioxygenase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17581819/ · DOI 10.1074/jbc.M703089200

evidence_access

Primary abstract

experimental_model

Human liver cDNA expressed in bacteria; activity compared with purified liver enzyme.

limitations

Conjugated bile acid and free taurine are separate molecules.

nutrient_topic

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

plain_language

Taurine becomes chemically attached to bile acids.

primary_references

Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8034703/

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 297–303

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human liver cDNA expressed in bacteria; activity compared with purified liver enzyme. · source_derived_draft · unverified_draft

## taurine-baat-taurine Taurine becomes chemically attached to bile acids. Expression of cloned human BAAT produced bile acid conjugation activity using taurine, establishing that the enzyme can make taurine-conjugated cholic acid from its activated CoA substrate. Model: Human liver cDNA expressed in bacteria; activity compared with purified liver enzyme. Limitations: Conjugated bile acid and free taurine are separate molecules. Evidence access: Primary abstract Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8034703/

evidence_span

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experimental_model

Human CHAT genetics, recombinant expression and enzyme kinetics

exposure

Ten recessive variants in five patients; nine mutant proteins assayed

limitations

Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates.

nutrient_topic

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

organism

Human CHAT proteins; COS-cell and bacterial expression systems

plain_language

The neurotransmitter needs both the choline headgroup and an acetyl group supplied by acetyl-CoA.

primary_references

[choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017

tissue_or_cell_type

Neuromuscular acetylcholine resynthesis

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 412–423

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHAT genetics, recombinant expression and enzyme kinetics · source_derived_draft · unverified_draft

### choline-chat-acetylcholine ChAT catalyzes reversible acetylcholine synthesis from choline and acetyl-CoA. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The neurotransmitter needs both the choline headgroup and an acetyl group supplied by acetyl-CoA. organism: Human CHAT proteins; COS-cell and bacterial expression systems tissue_or_cell_type: Neuromuscular acetylcholine resynthesis experimental_model: Human CHAT genetics, recombinant expression and enzyme kinetics limitations: Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates. exposure: Ten recessive variants in five patients; nine mutant proteins assayed evidence_span: {"source_cache": "artifacts/choline-research/11172068.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39", "start_char": 0, "end_char": 1231, "text_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39"} [choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017

evidence_span

{"source_cache": "artifacts/ibuprofen-research/1676645.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543", "start_char": 0, "end_char": 1438, "text_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543"}

experimental_model

Deuterium labelling with stereoselective gas chromatography and mass spectrometry in male Sprague-Dawley rats

exposure

R-ibuprofen and R-ring-2H4;2-2H ibuprofen at 7.5 milligrams per kilogram each, given orally together

limitations

The isotope design pins the chemistry: it shows which hydrogen is lost, that losing it is not rate-limiting, and that the intermediate is symmetrical. A rat study.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Rat

plain_language

The molecule loses one hydrogen, passes through a shape with no handedness at all, and can come out either way.

primary_references

[ibu-p1676645] Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat. (1991). https://pubmed.ncbi.nlm.nih.gov/1676645/ DOI: 10.1016/s0090-9556(25)07135-1

tissue_or_cell_type

Plasma and urine

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 84–95

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Deuterium labelling with stereoselective gas chromatography and mass spectrometry in male Sprague-Dawley rats · source_derived_draft · unverified_draft

### ibu-symmetrical-intermediate Chiral inversion of deuterium-labelled R-ibuprofen in the rat yields S-ibuprofen in a process involving quantitative loss of the deuterium atom originally at C-2, labelling at C-2 introduces no measurable kinetic deuterium isotope effect, and metabolism leads to the appearance of R-ibuprofen molecules labelled with four deuteriums, on which basis the proposed mechanism invokes stereoselective formation of the coenzyme A thioester of R-ibuprofen and its conversion to the corresponding enolate tautomer, affording a symmetrical intermediate through which racemization occurs in vivo. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The molecule loses one hydrogen, passes through a shape with no handedness at all, and can come out either way. organism: Rat tissue_or_cell_type: Plasma and urine experimental_model: Deuterium labelling with stereoselective gas chromatography and mass spectrometry in male Sprague-Dawley rats limitations: The isotope design pins the chemistry: it shows which hydrogen is lost, that losing it is not rate-limiting, and that the intermediate is symmetrical. A rat study. exposure: R-ibuprofen and R-ring-2H4;2-2H ibuprofen at 7.5 milligrams per kilogram each, given orally together evidence_span: {"source_cache": "artifacts/ibuprofen-research/1676645.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543", "start_char": 0, "end_char": 1438, "text_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543"} [ibu-p1676645] Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat. (1991). https://pubmed.ncbi.nlm.nih.gov/1676645/ DOI: 10.1016/s0090-9556(25)07135-1

evidence_span

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experimental_model

Purified recombinant enzyme substrate-specificity study

exposure

Serotonin and radiolabeled acetyl-CoA; product HPLC

limitations

Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.

nutrient_topic

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

organism

Human AANAT expressed in bacteria

plain_language

Serotonin is modified before it becomes melatonin.

primary_references

[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

tissue_or_cell_type

Serotonin acetylation

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 175–186

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

### melatonin-aanat-serotonin Human AANAT transferred an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Serotonin is modified before it becomes melatonin. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

cross_nutrient

B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation.

evidence

[{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Intact/permeabilized rat hepatocytes and liver preparations.

limitations

Whole-pathway requirements cannot all be assigned to the isolated lyase.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

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

organism

Rattus norvegicus

plain_language

ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD.

primary_references

[foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200

tissue_or_cell_type

Liver

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1003–1015

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intact/permeabilized rat hepatocytes and liver preparations. · source_derived_draft · unverified_draft

### b1-alpha-oxidation-activation-before-cleavage Rat liver/hepatocyte pathway experiments supported activation of 2-hydroxy-fatty acid to its CoA ester before ThDP-dependent cleavage; whole-pathway assays required ATP, CoA, Mg2+, ThDP and NAD+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Intact/permeabilized rat hepatocytes and liver preparations. limitations: Whole-pathway requirements cannot all be assigned to the isolated lyase. evidence: [{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation. nutrient: Thiamine (vitamin B1) [foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200

cross_nutrient

B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH.

evidence

[{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human recombinant component reconstitution.

limitations

Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

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

organism

Homo sapiens

plain_language

Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme.

primary_references

[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

tissue_or_cell_type

Purified complex

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 869–881

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

### b1-dhtkd1-recruits-shared-dlst-dld Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme. organism: Homo sapiens tissue_or_cell_type: Purified complex experimental_model: Human recombinant component reconstitution. limitations: Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH. nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

cross_nutrient

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

evidence

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

experimental_model

Reconstituted human multienzyme assay.

limitations

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

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Purified enzyme complex

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

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

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

evidence_access

Primary full text

experimental_model

Purified human GLYAT haplotypes, two-substrate kinetic analysis.

limitations

Reaction uses an activated acyl-CoA, not free benzoate; pathway activation and CoA release remain separate steps.

nutrient_topic

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

plain_language

Activated acyl groups can be transferred onto glycine for disposal.

primary_references

Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33803916/ · DOI 10.3390/ijms22063129

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 274–280

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human GLYAT haplotypes, two-substrate kinetic analysis. · source_derived_draft · unverified_draft

## glycine-glyat-benzoyl Activated acyl groups can be transferred onto glycine for disposal. Recombinant human GLYAT variants conjugated glycine to benzoyl-CoA in kinetic assays, forming the glycine-conjugation product hippurate. Model: Purified human GLYAT haplotypes, two-substrate kinetic analysis. Limitations: Reaction uses an activated acyl-CoA, not free benzoate; pathway activation and CoA release remain separate steps. Evidence access: Primary full text Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33803916/ · DOI 10.3390/ijms22063129

evidence_access

Primary full-text Figure 3 and enzyme experiments

experimental_model

E. timonensis enzymes; recombinant expression and reconstitution.

limitations

Acetyl-CoA was preferred among tested donors; in vivo donor use can differ.

nutrient_topic

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

plain_language

The microbial route first activates its substrate with CoA.

primary_references

Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 370–376

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · E. timonensis enzymes; recombinant expression and reconstitution. · source_derived_draft · unverified_draft

## l-carnitine-bbu-coa The microbial route first activates its substrate with CoA. Purified BbuB and BbuC together transferred CoA onto gamma-butyrobetaine; neither component alone reproduced the tested activity. Model: E. timonensis enzymes; recombinant expression and reconstitution. Limitations: Acetyl-CoA was preferred among tested donors; in vivo donor use can differ. Evidence access: Primary full-text Figure 3 and enzyme experiments Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118

evidence_access

Primary abstract and reviewed UniProt catalytic-reaction record

experimental_model

Human heart/muscle isoform in Pichia mitochondria; canonical reaction also recorded in UniProt Q92523/Rhea 12661.

limitations

This isoform assay does not measure whole-body fat loss.

nutrient_topic

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

plain_language

The outer-membrane enzyme loads a fatty-acid group onto carnitine.

primary_references

Functional studies of yeast-expressed human heart muscle carnitine palmitoyltransferase I. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9344464/ · DOI 10.1006/abbi.1997.0314

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 90–96

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human heart/muscle isoform in Pichia mitochondria; canonical reaction also recorded in UniProt Q92523/Rhea 12661. · source_derived_draft · unverified_draft

## l-carnitine-cpt1-transfer The outer-membrane enzyme loads a fatty-acid group onto carnitine. Human CPT1B expressed in yeast catalyzed transfer from palmitoyl-CoA onto carnitine, forming palmitoylcarnitine and releasing CoA. Model: Human heart/muscle isoform in Pichia mitochondria; canonical reaction also recorded in UniProt Q92523/Rhea 12661. Limitations: This isoform assay does not measure whole-body fat loss. Evidence access: Primary abstract and reviewed UniProt catalytic-reaction record Functional studies of yeast-expressed human heart muscle carnitine palmitoyltransferase I. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9344464/ · DOI 10.1006/abbi.1997.0314

evidence_access

Primary abstract and reviewed UniProt catalytic-reaction record

experimental_model

Human CPT2 in yeast homogenates; physiological direction from reviewed UniProt P23786/Rhea 12663.

limitations

The experiment directly measured the reverse reaction; direction in a cell depends on compartment and substrates.

nutrient_topic

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

plain_language

The inner enzyme unloads the fatty-acid group and recycles carnitine.

primary_references

Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 106–112

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CPT2 in yeast homogenates; physiological direction from reviewed UniProt P23786/Rhea 12663. · source_derived_draft · unverified_draft

## l-carnitine-cpt2-return The inner enzyme unloads the fatty-acid group and recycles carnitine. Expressed human CPT2 formed medium- and long-chain acylcarnitines from acyl-CoAs; its physiological matrix-side reaction reconverts incoming acylcarnitines to acyl-CoAs plus free carnitine. Model: Human CPT2 in yeast homogenates; physiological direction from reviewed UniProt P23786/Rhea 12663. Limitations: The experiment directly measured the reverse reaction; direction in a cell depends on compartment and substrates. Evidence access: Primary abstract and reviewed UniProt catalytic-reaction record Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002

evidence_access

Primary abstract and full-text Figures 1-4

experimental_model

Muscle-specific mouse knockout, enzyme assays and metabolomics.

limitations

Crat buffer function depends on tissue and substrate conditions.

nutrient_topic

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

plain_language

Carnitine can carry excess acetyl groups as well as long fatty-acid groups.

primary_references

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 154–160

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Muscle-specific mouse knockout, enzyme assays and metabolomics. · source_derived_draft · unverified_draft

## l-carnitine-crat-buffer Carnitine can carry excess acetyl groups as well as long fatty-acid groups. Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine. Model: Muscle-specific mouse knockout, enzyme assays and metabolomics. Limitations: Crat buffer function depends on tissue and substrate conditions. Evidence access: Primary abstract and full-text Figures 1-4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

evidence_access

Primary full-text Figure 4

experimental_model

Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay.

limitations

The effect is context-dependent; liver mitochondria also lacked the stimulation.

nutrient_topic

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

plain_language

Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation.

primary_references

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 162–168

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. · source_derived_draft · unverified_draft

## l-carnitine-crat-pdh Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation. Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria. Model: Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. Limitations: The effect is context-dependent; liver mitochondria also lacked the stimulation. Evidence access: Primary full-text Figure 4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

evidence_access

Primary full-text Figure 5 and enzyme assays

experimental_model

Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation.

limitations

Compartment and substrate supply may explain why this enzyme dominates in these cells.

nutrient_topic

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

plain_language

Another carnitine enzyme provided this carbon route.

primary_references

Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 218–224

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation. · source_derived_draft · unverified_draft

## l-carnitine-crot-knockout Another carnitine enzyme provided this carbon route. Deleting CROT reduced labeling of acetyl-CoA and palmitate from exogenous acetylcarnitine; CROT cDNA rescue restored acetyl-CoA labeling. Model: Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation. Limitations: Compartment and substrate supply may explain why this enzyme dominates in these cells. Evidence access: Primary full-text Figure 5 and enzyme assays Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

evidence_access

Primary abstract and full-text genetic/pharmacologic experiments

experimental_model

Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1.

limitations

Etomoxiryl-CoA formation was the proposed depletion mechanism; not evidence that carnitine depletes CoA.

nutrient_topic

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

plain_language

The experiment exposed a CoA-related off-target effect.

primary_references

Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 450–456

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1. · source_derived_draft · unverified_draft

## l-carnitine-etomoxir-coa The experiment exposed a CoA-related off-target effect. High etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression. Model: Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1. Limitations: Etomoxiryl-CoA formation was the proposed depletion mechanism; not evidence that carnitine depletes CoA. Evidence access: Primary abstract and full-text genetic/pharmacologic experiments Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001

evidence_access

Primary full-text Table 1 and recombinant enzyme methods

experimental_model

Human CRAT expressed in E. coli; steady-state kinetic substrate panel.

limitations

Purified-enzyme capacity does not identify the dominant flux in every compartment.

nutrient_topic

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

plain_language

The human enzyme directly connects carnitine and the CoA pool.

primary_references

Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 498–504

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CRAT expressed in E. coli; steady-state kinetic substrate panel. · source_derived_draft · unverified_draft

## l-carnitine-human-crat-reaction The human enzyme directly connects carnitine and the CoA pool. Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays. Model: Human CRAT expressed in E. coli; steady-state kinetic substrate panel. Limitations: Purified-enzyme capacity does not identify the dominant flux in every compartment. Evidence access: Primary full-text Table 1 and recombinant enzyme methods Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

evidence_access

Primary abstract

experimental_model

Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine.

limitations

Restoration of mitochondrial free CoA was a proposed mechanism, not directly measured.

nutrient_topic

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

plain_language

Acyl-group disposal can consume and export carnitine.

primary_references

L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6725560/ · DOI 10.1172/JCI111387

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 250–256

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine. · source_derived_draft · unverified_draft

## l-carnitine-organic-acid-export Acyl-group disposal can consume and export carnitine. Giving L-carnitine to three patients with propionic acidemia increased urinary propionylcarnitine, verified by mass spectrometry. Model: Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine. Limitations: Restoration of mitochondrial free CoA was a proposed mechanism, not directly measured. Evidence access: Primary abstract L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6725560/ · DOI 10.1172/JCI111387

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements.

limitations

A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

Restoring one nutrient repaired one branch but left another branch short of its other substrate.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 324–330

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. · source_derived_draft · unverified_draft

## l-cysteine-b5-blocks-coa-recovery Restoring one nutrient repaired one branch but left another branch short of its other substrate. After seven days of cysteine depletion, Cse-null mice repleted with cysteine but kept B5-deficient had persistently lower CoA and less weight recovery than mice receiving both nutrients, despite restored liver glutathione. Model: Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. Limitations: A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse sequential nutrient-depletion/repletion experiment.

limitations

The endpoint was recovery from induced wasting, not weight gain or energy improvement in healthy people. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

A second missing nutrient limited recovery after the first was restored.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 332–338

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse sequential nutrient-depletion/repletion experiment. · source_derived_draft · unverified_draft

## l-cysteine-b5-restores-weight-recovery A second missing nutrient limited recovery after the first was restored. Adding B5 to drinking water after seven days on the cysteine-sufficient, B5-deficient recovery diet promptly rescued the weight-recovery difference. Model: Mouse sequential nutrient-depletion/repletion experiment. Limitations: The endpoint was recovery from induced wasting, not weight gain or energy improvement in healthy people. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse tissue/urine metabolomics during combined genetic and dietary depletion.

limitations

Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

The shortage affected how efficiently the animal retained and used fuel.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 316–322

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse tissue/urine metabolomics during combined genetic and dietary depletion. · source_derived_draft · unverified_draft

## l-cysteine-depletion-carbon-loss The shortage affected how efficiently the animal retained and used fuel. Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism. Model: Mouse tissue/urine metabolomics during combined genetic and dietary depletion. Limitations: Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7.

limitations

CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 308–314

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. · source_derived_draft · unverified_draft

## l-cysteine-depletion-coa A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant. Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes. Model: Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. Limitations: CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Genetically engineered mice with established pancreatic tumors.

limitations

Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention.

nutrient_topic

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

plain_language

A transporter dependency could be targeted in this animal cancer model.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genetically engineered mice with established pancreatic tumors. · source_derived_draft · unverified_draft

## l-cysteine-mouse-pdac-import-loss A transporter dependency could be targeted in this animal cancer model. Deleting Slc7a11 in established genetically engineered mouse PDAC induced tumor-selective ferroptosis and inhibited growth. Model: Genetically engineered mice with established pancreatic tumors. Limitations: Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays.

limitations

Culture starvation is not dietary treatment; one of the tested lines differed.

nutrient_topic

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

plain_language

Dependence on external sulfur varied between cancer-cell models.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. · source_derived_draft · unverified_draft

## l-cysteine-pdac-cystine-withdrawal Dependence on external sulfur varied between cancer-cell models. Cystine starvation induced lipid oxidation and ferroptosis in four of five tested human PDAC cell lines. Model: Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. Limitations: Culture starvation is not dietary treatment; one of the tested lines differed. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC culture; pharmacological PANKi/BSO combination.

limitations

This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy.

nutrient_topic

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

plain_language

Two protective branches were experimentally blocked together.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture; pharmacological PANKi/BSO combination. · source_derived_draft · unverified_draft

## l-cysteine-pdac-dual-block Two protective branches were experimentally blocked together. Pantothenate-kinase inhibition combined with BSO synergistically induced ferroptosis in the reported PDAC assays. Model: Human PDAC culture; pharmacological PANKi/BSO combination. Limitations: This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC cultures, BSO and viability/lipid-ROS assays.

limitations

This null result is model-specific; it does not make glutathione dispensable in general.

nutrient_topic

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

plain_language

Loss of glutathione alone did not explain the whole cysteine-depletion effect.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures, BSO and viability/lipid-ROS assays. · source_derived_draft · unverified_draft

## l-cysteine-pdac-gsh-only-limit Loss of glutathione alone did not explain the whole cysteine-depletion effect. Buthionine sulfoximine lowered glutathione without inducing lipid oxidation or loss of viability under the tested PDAC conditions. Model: Human PDAC cultures, BSO and viability/lipid-ROS assays. Limitations: This null result is model-specific; it does not make glutathione dispensable in general. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

experimental_model

Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures

limitations

Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1.

organism

Homo sapiens

plain_language

The four-carbon intermediate is split into two acetyl-CoA molecules.

primary_references

[haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192

tissue_or_cell_type

Mitochondrial matrix enzyme; recombinant protein study

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 377–385

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures · source_derived_draft · unverified_draft

### acat1-acetoacetyl-coa-thiolysis Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules. Plain language: The four-carbon intermediate is split into two acetyl-CoA molecules. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix enzyme; recombinant protein study experimental_model: Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures limitations: Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1. [haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192

experimental_model

Human p300 catalytic-domain structure and biochemical assays.

limitations

This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

Acetyl groups can be written onto lysines already present in proteins.

primary_references

[p300-2008] The structural basis of protein acetylation by the p300/CBP transcriptional coactivator (2008). https://pubmed.ncbi.nlm.nih.gov/18273021/ DOI: 10.1038/nature06546

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 527–535

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human p300 catalytic-domain structure and biochemical assays. · source_derived_draft · unverified_draft

### ep300-lysine-acetylation EP300 transfers an acetyl group from acetyl-CoA to a protein lysine side chain. Plain language: Acetyl groups can be written onto lysines already present in proteins. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human p300 catalytic-domain structure and biochemical assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [p300-2008] The structural basis of protein acetylation by the p300/CBP transcriptional coactivator (2008). https://pubmed.ncbi.nlm.nih.gov/18273021/ DOI: 10.1038/nature06546

experimental_model

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

limitations

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Mitochondrial matrix

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

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

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

cross_nutrient

B5-derived CoA supplies phosphopantetheine; direct CoA handoff tested, dietary B5 link upstream.

experimental_model

Reconstitution and site-directed mutagenesis

exposure

Assay conditions described in the linked primary study.

limitations

Does not establish dietary B5 deficiency or repletion effects.

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

A CoA-derived arm prepares the folate enzyme for catalysis.

primary_references

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

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1046–1057

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

### aldh1l2-coa-arm Human phosphopantetheinyl transferase transfers a CoA-derived prosthetic group to ALDH1L2 Ser375. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A CoA-derived arm prepares the folate enzyme for catalysis. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Reconstitution and site-directed mutagenesis limitations: Does not establish dietary B5 deficiency or repletion effects. exposure: Assay conditions described in the linked primary study. cross_nutrient: B5-derived CoA supplies phosphopantetheine; direct CoA handoff tested, dietary B5 link upstream. [strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008

cross_nutrient

false

experimental_model

Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays

exposure

PI3K–AKT signalling and PANK4 phosphorylation manipulations; no nutrient dosing trial.

limitations

Primary abstract with supporting cellular assays; mechanism is not a rationale for treating insulin signalling or increasing B5 intake.

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

Growth-factor signalling can ease the PANK4 brake on CoA production.

primary_references

[b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8

tissue_or_cell_type

Human cultured-cell models

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 691–702

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays · source_derived_draft · unverified_draft

### b5-bio-akt-pank4-regulation AKT phosphorylation of PANK4 relieved its suppression of de novo CoA synthesis in the study models. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Growth-factor signalling can ease the PANK4 brake on CoA production. organism: Homo sapiens tissue_or_cell_type: Human cultured-cell models experimental_model: Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays limitations: Primary abstract with supporting cellular assays; mechanism is not a rationale for treating insulin signalling or increasing B5 intake. exposure: PI3K–AKT signalling and PANK4 phosphorylation manipulations; no nutrient dosing trial. cross_nutrient: false [b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies

exposure

Two affected individuals versus one healthy-control fibroblast line; four independent experiments shown in Fig. 6.

limitations

Small cell-line comparison and an absence of statistical significance, not proof of equal CoA in all compartments or tissues. Acetyl-CoA was significantly lower in one case; total-CoA trends and free-CoA results must not be conflated.

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

A severe enzyme defect did not imply an absent whole-cell free-CoA pool in these fibroblasts.

primary_references

[b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008

tissue_or_cell_type

Human primary skin fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 743–754

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies · source_derived_draft · unverified_draft

### b5-bio-coasy-fibroblast-free-coa Free-CoA levels in fibroblasts from the two COASY cases were not significantly different from the control in the reported HPLC analysis. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A severe enzyme defect did not imply an absent whole-cell free-CoA pool in these fibroblasts. organism: Homo sapiens tissue_or_cell_type: Human primary skin fibroblasts experimental_model: Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies limitations: Small cell-line comparison and an absence of statistical significance, not proof of equal CoA in all compartments or tissues. Acetyl-CoA was significantly lower in one case; total-CoA trends and free-CoA results must not be conflated. exposure: Two affected individuals versus one healthy-control fibroblast line; four independent experiments shown in Fig. 6. cross_nutrient: false [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008

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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies

exposure

HPLC assays with 1 microgram recombinant wild-type or p.Arg499Cys DPCK protein, ATP and dephospho-CoA; substrate concentrations not extracted.

limitations

Loss of detectable isolated-domain activity does not mean that every patient cell has no CoA. Wild-type and variant domains were recombinantly produced in bacteria.

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

This COASY variant disabled the final reaction in the isolated-enzyme test.

primary_references

[b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008

tissue_or_cell_type

Purified recombinant protein; no intact tissue

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 730–741

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies · source_derived_draft · unverified_draft

### b5-bio-coasy-r499c-activity The recombinant COASY DPCK domain carrying p.Arg499Cys did not produce a detectable CoA HPLC peak, whereas wild-type DPCK converted dephospho-CoA to CoA. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This COASY variant disabled the final reaction in the isolated-enzyme test. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies limitations: Loss of detectable isolated-domain activity does not mean that every patient cell has no CoA. Wild-type and variant domains were recombinantly produced in bacteria. exposure: HPLC assays with 1 microgram recombinant wild-type or p.Arg499Cys DPCK protein, ATP and dephospho-CoA; substrate concentrations not extracted. cross_nutrient: false [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

C57/BL6 Pank2-null mice, both sexes aged 3–6 months, with globus-pallidus-enriched brain dissection; human PKAN cell experiments

exposure

Oral 4′-phosphopantetheine in 10% sucrose for 14 days; efficacy regimen 5 micrograms/g body weight (5 mg/kg); both-sex Pank2-null C57/BL6 mice aged 3–6 months; Fig. 2E n=5 per genotype/treatment group.

limitations

Biochemical rescue in mice, not a human efficacy result or proof of intact blood–brain-barrier delivery. The tissue was GP-enriched, not purified GP. Loss of Pank2 is machinery impairment, not dietary B5 withdrawal.

nutrient_topic

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

organism

Mus musculus

plain_language

A downstream intermediate improved a mitochondrial enzyme measurement in this genetic mouse model.

primary_references

[b5-bio-salvage2019] 4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN. (2019). https://pubmed.ncbi.nlm.nih.gov/31660701/ DOI: 10.15252/emmm.201910489

tissue_or_cell_type

Globus-pallidus-enriched brain region; crude dissection also included neighboring structures

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 782–793

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · C57/BL6 Pank2-null mice, both sexes aged 3–6 months, with globus-pallidus-enriched brain dissection; human PKAN cell experiments · source_derived_draft · unverified_draft

### b5-bio-pank2-model-complex-i-rescue Oral 4′-phosphopantetheine corrected the complex I activity defect in globus-pallidus-enriched brain tissue from Pank2-null mice. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A downstream intermediate improved a mitochondrial enzyme measurement in this genetic mouse model. organism: Mus musculus tissue_or_cell_type: Globus-pallidus-enriched brain region; crude dissection also included neighboring structures experimental_model: C57/BL6 Pank2-null mice, both sexes aged 3–6 months, with globus-pallidus-enriched brain dissection; human PKAN cell experiments limitations: Biochemical rescue in mice, not a human efficacy result or proof of intact blood–brain-barrier delivery. The tissue was GP-enriched, not purified GP. Loss of Pank2 is machinery impairment, not dietary B5 withdrawal. exposure: Oral 4′-phosphopantetheine in 10% sucrose for 14 days; efficacy regimen 5 micrograms/g body weight (5 mg/kg); both-sex Pank2-null C57/BL6 mice aged 3–6 months; Fig. 2E n=5 per genotype/treatment group. cross_nutrient: false [b5-bio-salvage2019] 4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN. (2019). https://pubmed.ncbi.nlm.nih.gov/31660701/ DOI: 10.15252/emmm.201910489

cross_nutrient

false

experimental_model

Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays

exposure

Wild-type versus D623A or D659A PANK4 re-expression; 3-hour carbon-13/nitrogen-15 vitamin-B5 labelling with growth factors.

limitations

Engineered cellular PI3K–AKT context; isotope concentration not verified. No claim that PANK4 controls every tissue or that dietary B5 produces the same response.

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

PANK4 phosphatase activity can reduce new CoA production in cultured cells.

primary_references

[b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8

tissue_or_cell_type

Human MCF10A mammary epithelial cells

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 678–689

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays · source_derived_draft · unverified_draft

### b5-bio-pank4-flux-suppression Re-expression of active PANK4 in PANK4-knockout AKT p.E17K/+ MCF10A cells suppressed newly synthesized CoA, whereas phosphatase-inactive mutants did not reproduce the suppression. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PANK4 phosphatase activity can reduce new CoA production in cultured cells. organism: Homo sapiens tissue_or_cell_type: Human MCF10A mammary epithelial cells experimental_model: Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays limitations: Engineered cellular PI3K–AKT context; isotope concentration not verified. No claim that PANK4 controls every tissue or that dietary B5 produces the same response. exposure: Wild-type versus D623A or D659A PANK4 re-expression; 3-hour carbon-13/nitrogen-15 vitamin-B5 labelling with growth factors. cross_nutrient: false [b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8

cross_nutrient

false

experimental_model

Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments

exposure

Extracellular 4′-phosphopantetheine/CoA exposure; concentrations not extracted.

limitations

Author mechanistic interpretation preserved as a hypothesis. Abstract-only extraction cannot exclude extracellular dephosphorylation/rephosphorylation or establish passive uptake in every tissue, serum stability, or blood–brain-barrier delivery.

nutrient_topic

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

organism

Eukaryotic cell/organism models; assay-level species not specified in abstract

plain_language

The authors proposed direct entry of the intermediate; the transport route remains a separate question from downstream enzyme activity.

primary_references

[b5-bio-salvage2015] Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26322826/ DOI: 10.1038/nchembio.1906

tissue_or_cell_type

Cell membrane and intracellular CoA synthesis

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 769–780

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments · source_derived_draft · unverified_draft

### b5-bio-phosphopantetheine-entry-proposal The 2015 salvage paper interpreted its experiments as passive membrane entry of extracellular 4′-phosphopantetheine before conversion back to CoA. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The authors proposed direct entry of the intermediate; the transport route remains a separate question from downstream enzyme activity. organism: Eukaryotic cell/organism models; assay-level species not specified in abstract tissue_or_cell_type: Cell membrane and intracellular CoA synthesis experimental_model: Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments limitations: Author mechanistic interpretation preserved as a hypothesis. Abstract-only extraction cannot exclude extracellular dephosphorylation/rephosphorylation or establish passive uptake in every tissue, serum stability, or blood–brain-barrier delivery. exposure: Extracellular 4′-phosphopantetheine/CoA exposure; concentrations not extracted. cross_nutrient: false [b5-bio-salvage2015] Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26322826/ DOI: 10.1038/nchembio.1906

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

BioC text lines 11, 51; Fig. 2A–B

experimental_model

ACLY and/or AceCS1 siRNA with acetate supplementation

exposure

0, 1 or 5 mM acetate for 24 hours before lysis after siRNA treatment.

limitations

The authors identify this acetate supply as supraphysiologic; it is not a dietary recommendation and does not show rescue of an absent CoA pool. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

A second acetyl-CoA-producing route could compensate when enough acetate was supplied.

primary_references

[b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097

tissue_or_cell_type

HCT116 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1005–1017

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ACLY and/or AceCS1 siRNA with acetate supplementation · source_derived_draft · unverified_draft

### b5-met-acetate-acss2-histone-rescue Extracellular acetate restored histone acetylation in ACLY-silenced HCT116 cells in a dose-dependent manner that required AceCS1, now named ACSS2. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second acetyl-CoA-producing route could compensate when enough acetate was supplied. organism: Homo sapiens tissue_or_cell_type: HCT116 cells experimental_model: ACLY and/or AceCS1 siRNA with acetate supplementation limitations: The authors identify this acetate supply as supraphysiologic; it is not a dietary recommendation and does not show rescue of an absent CoA pool. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 0, 1 or 5 mM acetate for 24 hours before lysis after siRNA treatment. cross_nutrient: false evidence_location: BioC text lines 11, 51; Fig. 2A–B [b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097

cross_nutrient

false

evidence_location

Full text line 115; Fig. 2C

experimental_model

Oxidant washout in HEK293 cells stably overexpressing Pank1beta

exposure

500 micromolar H2O2 for 60 minutes, then recovery in complete growth medium.

limitations

The removal mechanism was not identified; engineered high-CoA cells are not ordinary circulating blood cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

The CoA modification receded when the oxidative exposure ended.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Engineered HEK293 cultures

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1061–1073

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxidant washout in HEK293 cells stably overexpressing Pank1beta · source_derived_draft · unverified_draft

### b5-met-coalation-reversal After removal of hydrogen peroxide from HEK293/Pank1beta cultures, induced protein CoAlation declined within 5 minutes and returned to baseline within 90 minutes. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoA modification receded when the oxidative exposure ended. organism: Homo sapiens tissue_or_cell_type: Engineered HEK293 cultures experimental_model: Oxidant washout in HEK293 cells stably overexpressing Pank1beta limitations: The removal mechanism was not identified; engineered high-CoA cells are not ordinary circulating blood cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 500 micromolar H2O2 for 60 minutes, then recovery in complete growth medium. cross_nutrient: false evidence_location: Full text line 115; Fig. 2C [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text lines 107, 123–125; Fig. 4F–G; Extended Data Fig. 5G–H

experimental_model

Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing

exposure

Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. Carbon-13 glucose tracing followed by LC-MS.

limitations

The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Human HCI002 grafts in Mus musculus hosts

plain_language

B5 restriction also reduced the measured labeled acetyl-CoA formed from glucose in these tumors.

primary_references

[b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

tissue_or_cell_type

Orthotopic HCI002 tumor tissue

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing · source_derived_draft · unverified_draft

### b5-met-diet-hci002-acetylcoa Pantothenate deprivation reduced the amount of glucose-derived carbon-13-labeled acetyl-CoA in HCI002 xenografts. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: B5 restriction also reduced the measured labeled acetyl-CoA formed from glucose in these tumors. organism: Human HCI002 grafts in Mus musculus hosts tissue_or_cell_type: Orthotopic HCI002 tumor tissue experimental_model: Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing limitations: The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. Carbon-13 glucose tracing followed by LC-MS. cross_nutrient: true evidence_location: Full text lines 107, 123–125; Fig. 4F–G; Extended Data Fig. 5G–H [b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Abstract, later phenotypic changes

experimental_model

Mitochondrial ACP siRNA in HEK293T cells

exposure

ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown.

limitations

Temporal ordering alone does not separate all direct complex-I effects from secondary cellular injury; abstract-level extraction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

The carrier-protein defect also impaired complex I function.

primary_references

[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

tissue_or_cell_type

HEK293T mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 837–849

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft

### b5-met-mtacp-complex-i Mitochondrial ACP knockdown in HEK293T cells subsequently reduced respiratory complex I specific activity. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier-protein defect also impaired complex I function. organism: Homo sapiens tissue_or_cell_type: HEK293T mitochondria experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Temporal ordering alone does not separate all direct complex-I effects from secondary cellular injury; abstract-level extraction. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown. cross_nutrient: false evidence_location: Abstract, later phenotypic changes [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

cross_nutrient

false

evidence_location

Full text lines 105–107; Fig. 1B–D

experimental_model

Primary cardiomyocyte exposure and Langendorff-perfused rat hearts

exposure

Cardiomyocytes: 1–100 micromolar H2O2, 30 minutes; perfused hearts: 100 micromolar H2O2, 20 minutes.

limitations

DTT sensitivity supports mixed disulfides. Antioxidant protection or improved organ function was not established by this endpoint. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Oxidative stress caused CoA to form reversible bonds with protein cysteines.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Adult cardiomyocytes and isolated heart

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1047–1059

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary cardiomyocyte exposure and Langendorff-perfused rat hearts · source_derived_draft · unverified_draft

### b5-met-oxidant-coalation Hydrogen peroxide exposure induced DTT-sensitive protein CoAlation in isolated rat cardiomyocytes and perfused rat hearts. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidative stress caused CoA to form reversible bonds with protein cysteines. organism: Rattus norvegicus tissue_or_cell_type: Adult cardiomyocytes and isolated heart experimental_model: Primary cardiomyocyte exposure and Langendorff-perfused rat hearts limitations: DTT sensitivity supports mixed disulfides. Antioxidant protection or improved organ function was not established by this endpoint. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiomyocytes: 1–100 micromolar H2O2, 30 minutes; perfused hearts: 100 micromolar H2O2, 20 minutes. cross_nutrient: false evidence_location: Full text lines 105–107; Fig. 1B–D [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

cross_nutrient

false

evidence_location

Full text lines 33, 61 and 141; Fig. 6D

experimental_model

FLAG-PDK2 expressed in HEK293 cells, immunoprecipitated and assayed with porcine-heart PDH

exposure

1 mM CoA disulfide preincubation for 20 minutes; PDH phosphorylation assay with/without 2 mM DTT.

limitations

CoA disulfide is distinct from reduced CoA. The assay does not establish net mitochondrial PDH flux or a supplementation effect in vivo. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Human PDK2; Sus scrofa PDH assay substrate

plain_language

Adding CoA through a disulfide bond reversibly inhibited the kinase that regulates pyruvate dehydrogenase.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Cell-free kinase assay

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1089–1101

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · FLAG-PDK2 expressed in HEK293 cells, immunoprecipitated and assayed with porcine-heart PDH · source_derived_draft · unverified_draft

### b5-met-pdk2-coalation-inhibition In-vitro CoAlation of immunoprecipitated recombinant PDK2 reduced its phosphorylation of PDH E1, and DTT restored kinase activity. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding CoA through a disulfide bond reversibly inhibited the kinase that regulates pyruvate dehydrogenase. organism: Human PDK2; Sus scrofa PDH assay substrate tissue_or_cell_type: Cell-free kinase assay experimental_model: FLAG-PDK2 expressed in HEK293 cells, immunoprecipitated and assayed with porcine-heart PDH limitations: CoA disulfide is distinct from reduced CoA. The assay does not establish net mitochondrial PDH flux or a supplementation effect in vivo. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 1 mM CoA disulfide preincubation for 20 minutes; PDH phosphorylation assay with/without 2 mM DTT. cross_nutrient: false evidence_location: Full text lines 33, 61 and 141; Fig. 6D [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

cross_nutrient

true

evidence_location

Full text lines 29 and 117; Fig. 2E

experimental_model

Antioxidant pretreatment of engineered HEK293/Pank1beta cells

exposure

1 mM vitamin C for 2 hours before 0.5 mM diamide for 30 minutes.

limitations

The endpoint is protein anti-CoA immunoreactivity, not clinical benefit; lower CoAlation is not assumed universally beneficial. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

Vitamin C exposure blunted the measured CoA protein modification during this experimental oxidative challenge.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Engineered HEK293 cultures

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1075–1087

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Antioxidant pretreatment of engineered HEK293/Pank1beta cells · source_derived_draft · unverified_draft

### b5-met-vitc-coalation Vitamin C pretreatment reduced diamide-induced anti-CoA protein immunoreactivity by approximately 50% in HEK293/Pank1beta cells. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C exposure blunted the measured CoA protein modification during this experimental oxidative challenge. organism: Homo sapiens tissue_or_cell_type: Engineered HEK293 cultures experimental_model: Antioxidant pretreatment of engineered HEK293/Pank1beta cells limitations: The endpoint is protein anti-CoA immunoreactivity, not clinical benefit; lower CoAlation is not assumed universally beneficial. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 1 mM vitamin C for 2 hours before 0.5 mM diamide for 30 minutes. cross_nutrient: true evidence_location: Full text lines 29 and 117; Fig. 2E [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129