Choline

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"}

experimental_model

Four individuals, three families; patient-fibroblast transport and rescue

exposure

SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge

limitations

Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007).

nutrient_topic

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

organism

Human

plain_language

Extra choline improved the cell phenotype in this experiment.

primary_references

[choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376

tissue_or_cell_type

Patient fibroblasts; clinical neurodegeneration

trigger_kind

machinery_impairment Imported condition classification; unverified.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 386–397

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four individuals, three families; patient-fibroblast transport and rescue · source_derived_draft · unverified_draft

### choline-ctl1-cell-rescue Chronic choline treatment made mutant fibroblast ultrastructure resemble healthy control cells. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra choline improved the cell phenotype in this experiment. organism: Human tissue_or_cell_type: Patient fibroblasts; clinical neurodegeneration experimental_model: Four individuals, three families; patient-fibroblast transport and rescue limitations: Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007). exposure: SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge evidence_span: {"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"} [choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"}

experimental_model

Four individuals, three families; patient-fibroblast transport and rescue

exposure

SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge

limitations

Cultured-cell rescue under an acute challenge; does not establish clinical iron tolerance or a general choline–iron dosing rule.

nutrient_topic

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

organism

Human

plain_language

Choline handling and iron-stress resistance met in this cell model.

primary_references

[choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376

tissue_or_cell_type

Patient fibroblasts; clinical neurodegeneration

trigger_kind

machinery_impairment Imported condition classification; unverified.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 399–410

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four individuals, three families; patient-fibroblast transport and rescue · source_derived_draft · unverified_draft

### choline-ctl1-iron-rescue Choline treatment protected the mutant fibroblasts from acute iron overload. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline handling and iron-stress resistance met in this cell model. organism: Human tissue_or_cell_type: Patient fibroblasts; clinical neurodegeneration experimental_model: Four individuals, three families; patient-fibroblast transport and rescue limitations: Cultured-cell rescue under an acute challenge; does not establish clinical iron tolerance or a general choline–iron dosing rule. exposure: SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge evidence_span: {"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"} [choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Choline modifies a folate-genotype-associated phenotype.

experimental_model

Choline feeding and isotope tracing in women across reproductive states.

exposure

480 versus 930 mg/day; recommended folate intake

limitations

The matched reference is noncarriers at 480 mg/day, not noncarriers at the same 930 mg/day; subgroup result, not universal restoration or dosing advice.

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

Higher intake brought carriers to the lower-intake noncarrier reference value.

primary_references

[ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr

tissue_or_cell_type

Plasma tracer metabolites

trigger_kind

machinery_impairment Imported condition classification; unverified.

Folate and folic acid: mechanisms, 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 · Choline feeding and isotope tracing in women across reproductive states. · source_derived_draft · unverified_draft

### folate-methyl-choline-intake-variant In nonpregnant MTHFR rs1801133 carriers receiving 930 mg choline/day, the betaine-d9:PC-d9 enrichment ratio was 0.87, matching noncarriers receiving 480 mg/day (0.87); noncarriers receiving 930 mg/day had a ratio of 1.0. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher intake brought carriers to the lower-intake noncarrier reference value. organism: Homo sapiens tissue_or_cell_type: Plasma tracer metabolites experimental_model: Choline feeding and isotope tracing in women across reproductive states. limitations: The matched reference is noncarriers at 480 mg/day, not noncarriers at the same 930 mg/day; subgroup result, not universal restoration or dosing advice. exposure: 480 versus 930 mg/day; recommended folate intake cross_nutrient: Choline modifies a folate-genotype-associated phenotype. [ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr

evidence_span

{"source_cache": "artifacts/choline-research/38589607.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a", "start_char": 0, "end_char": 1090, "text_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a"}

experimental_model

Human CHT1 cryo-EM and functional characterization

exposure

Choline-bound, inhibitor-bound and apo conformations

limitations

Structural transport cycle; no claim of cognitive benefit from increasing intake.

nutrient_topic

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

organism

Human CHT1 protein

plain_language

After acetylcholine is broken down, choline can be taken back up and reused.

primary_references

[choline-p38589607] Transport mechanism of presynaptic high-affinity choline uptake by CHT1. (2024). https://pubmed.ncbi.nlm.nih.gov/38589607/ DOI: 10.1038/s41594-024-01259-w

tissue_or_cell_type

Presynaptic uptake mechanism and experimental structures

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 334–345

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 cryo-EM and functional characterization · source_derived_draft · unverified_draft

### choline-cht1-recycling CHT1 supports reutilization of choline liberated by synaptic acetylcholine hydrolysis, sustaining presynaptic acetylcholine synthesis. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: After acetylcholine is broken down, choline can be taken back up and reused. organism: Human CHT1 protein tissue_or_cell_type: Presynaptic uptake mechanism and experimental structures experimental_model: Human CHT1 cryo-EM and functional characterization limitations: Structural transport cycle; no claim of cognitive benefit from increasing intake. exposure: Choline-bound, inhibitor-bound and apo conformations evidence_span: {"source_cache": "artifacts/choline-research/38589607.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a", "start_char": 0, "end_char": 1090, "text_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a"} [choline-p38589607] Transport mechanism of presynaptic high-affinity choline uptake by CHT1. (2024). https://pubmed.ncbi.nlm.nih.gov/38589607/ DOI: 10.1038/s41594-024-01259-w

evidence_span

{"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"}

experimental_model

Human transporter expression, uptake, cryo-EM and mutagenesis

exposure

Choline/ethanolamine substrate challenges and purified transporter structures

limitations

Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms.

nutrient_topic

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

organism

Human proteins in experimental systems

plain_language

FLVCR1 can move choline across the cell boundary.

primary_references

[choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7

tissue_or_cell_type

Plasma-membrane transport

transport_effect

depends Recorded as concentration-driven transport, so the net direction follows the gradient.

transport_pool

the cytosol across the plasma membrane Recorded as concentration-driven transport, so the net direction follows the gradient.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 217–228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression, uptake, cryo-EM and mutagenesis · source_derived_draft · unverified_draft

### choline-flvcr1-choline Human FLVCR1 facilitated concentration-driven choline transport across the plasma membrane. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLVCR1 can move choline across the cell boundary. organism: Human proteins in experimental systems tissue_or_cell_type: Plasma-membrane transport experimental_model: Human transporter expression, uptake, cryo-EM and mutagenesis limitations: Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms. exposure: Choline/ethanolamine substrate challenges and purified transporter structures evidence_span: {"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"} [choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7

evidence_span

{"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"}

experimental_model

Human transporter expression, uptake, cryo-EM and mutagenesis

exposure

Choline/ethanolamine substrate challenges and purified transporter structures

limitations

Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms.

nutrient_topic

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

organism

Human proteins in experimental systems

plain_language

FLVCR2 can move choline across the cell boundary.

primary_references

[choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7

tissue_or_cell_type

Plasma-membrane transport

transport_effect

depends Recorded as concentration-driven transport, so the net direction follows the gradient.

transport_pool

the cytosol across the plasma membrane Recorded as concentration-driven transport, so the net direction follows the gradient.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 243–254

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression, uptake, cryo-EM and mutagenesis · source_derived_draft · unverified_draft

### choline-flvcr2-choline Human FLVCR2 facilitated concentration-driven choline transport across the plasma membrane. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLVCR2 can move choline across the cell boundary. organism: Human proteins in experimental systems tissue_or_cell_type: Plasma-membrane transport experimental_model: Human transporter expression, uptake, cryo-EM and mutagenesis limitations: Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms. exposure: Choline/ethanolamine substrate challenges and purified transporter structures evidence_span: {"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"} [choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Folate repletion modifies choline status.

experimental_model

Metabolic-unit depletion/repletion: 11 men, 10 women.

exposure

2-6 weeks folic-acid repletion

limitations

Not evidence folate replaces dietary choline.

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

Restoring folate improved the choline markers.

primary_references

[jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712

tissue_or_cell_type

Plasma

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 718–729

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit depletion/repletion: 11 men, 10 women. · source_derived_draft · unverified_draft

### folate-methyl-folate-choline-repletion Folate repletion returned depressed plasma choline-status measures to baseline or above in the low-choline feeding studies. Condition category: nutrient_deficiency nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring folate improved the choline markers. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Metabolic-unit depletion/repletion: 11 men, 10 women. limitations: Not evidence folate replaces dietary choline. exposure: 2-6 weeks folic-acid repletion cross_nutrient: Folate repletion modifies choline status. [jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Folate and choline status are coupled.

experimental_model

Metabolic-unit depletion/repletion: 11 men, 10 women.

exposure

Men: 25 micrograms folate/238 mg choline daily; women: 56 micrograms/147 mg

limitations

No functional choline deficiency by measured transaminase/lipid endpoints.

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

Folate restriction strained choline markers during low choline intake.

primary_references

[jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712

tissue_or_cell_type

Plasma

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 693–704

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit depletion/repletion: 11 men, 10 women. · source_derived_draft · unverified_draft

### folate-methyl-low-folate-choline Combined low-folate/low-choline feeding lowered plasma choline by 28% in men and 25% in women. Condition category: nutrient_deficiency nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate restriction strained choline markers during low choline intake. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Metabolic-unit depletion/repletion: 11 men, 10 women. limitations: No functional choline deficiency by measured transaminase/lipid endpoints. exposure: Men: 25 micrograms folate/238 mg choline daily; women: 56 micrograms/147 mg cross_nutrient: Folate and choline status are coupled. [jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712

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

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experimental_model

Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing

exposure

Biochemical pathway described in the study introduction

limitations

Established pathway background in this carrier study, not a newly isolated human CHDH catalytic assay. No cofactor identity or exclusive downstream ALDH isoform is inferred.

nutrient_topic

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

organism

Mammalian pathway background applied to the human-cell arm

plain_language

Choline oxidation has an aldehyde intermediate; it is not one undifferentiated jump to betaine.

primary_references

[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010

tissue_or_cell_type

Mitochondrial choline metabolism

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 464–475

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft

### choline-chdh-aldehyde-step The pathway model identifies CHDH-mediated oxidation of choline to betaine aldehyde upstream of aldehyde-dehydrogenase-mediated betaine production. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline oxidation has an aldehyde intermediate; it is not one undifferentiated jump to betaine. organism: Mammalian pathway background applied to the human-cell arm tissue_or_cell_type: Mitochondrial choline metabolism experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Established pathway background in this carrier study, not a newly isolated human CHDH catalytic assay. No cofactor identity or exclusive downstream ALDH isoform is inferred. exposure: Biochemical pathway described in the study introduction evidence_span: {"source_cache": "artifacts/choline-research/39111307.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "086a515ebf324a03baeb82e7fe21771eb7f819da09ef7a22372e06db25d3c571", "start_char": 3335, "end_char": 3656, "text_sha256": "580d72b54dac50ca5d1cfdb4e2ffe3719e957af76ac81d761422471424636d69"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010

evidence_span

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experimental_model

Human choline kinase alpha1 and pathogen-enzyme biochemical comparison

exposure

ATP-dependent choline phosphorylation in magnesium-containing assays

limitations

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

nutrient_topic

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

organism

Human alpha1 isoform; pathogen comparators remain separate

plain_language

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

primary_references

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

tissue_or_cell_type

Purified choline kinase active site

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

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

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

evidence_span

{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}

experimental_model

Human CHT1 expression in Xenopus oocytes

exposure

Choline, sodium and chloride titrations; hemicholinium-3 inhibition

limitations

Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.

nutrient_topic

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

organism

Human transporter; Xenopus oocyte host

plain_language

Cl− was part of the transport requirement, not just a background nutrient.

primary_references

[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

tissue_or_cell_type

Plasma-membrane transport assay

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 308–319

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft

### choline-cht1-chloride Human CHT1-mediated choline uptake depended on Cl− in the oocyte assay. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cl− was part of the transport requirement, not just a background nutrient. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

evidence_span

{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}

experimental_model

Human CHT1 expression in Xenopus oocytes

exposure

Choline, sodium and chloride titrations; hemicholinium-3 inhibition

limitations

Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.

nutrient_topic

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

organism

Human transporter; Xenopus oocyte host

plain_language

Na+ was part of the transport requirement, not just a background nutrient.

primary_references

[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

tissue_or_cell_type

Plasma-membrane transport assay

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 295–306

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft

### choline-cht1-sodium Human CHT1-mediated choline uptake depended on Na+ in the oocyte assay. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Na+ was part of the transport requirement, not just a background nutrient. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

evidence_span

{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}

experimental_model

Human CHT1 expression in Xenopus oocytes

exposure

Choline, sodium and chloride titrations; hemicholinium-3 inhibition

limitations

Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.

nutrient_topic

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

organism

Human transporter; Xenopus oocyte host

plain_language

This transporter supplies choline for the neuronal recycling route.

primary_references

[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

tissue_or_cell_type

Plasma-membrane transport assay

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 282–293

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft

### choline-cht1-uptake Human CHT1 expression produced high-affinity choline uptake in Xenopus oocytes. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This transporter supplies choline for the neuronal recycling route. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

evidence_span

{"source_cache": "artifacts/choline-research/23151509.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6", "start_char": 0, "end_char": 1160, "text_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6"}

experimental_model

Anaerobic bacterial genetics, heterologous expression and EPR

exposure

Genetic knockout and heterologous expression of choline-utilization genes

limitations

A bacterial enzyme pathway, not a direct human-enzyme reaction or evidence that every microbiome produces the same TMA amount.

nutrient_topic

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

organism

Desulfovibrio desulfuricans; E. coli expression host

plain_language

Gut microbial machinery can divert choline into a different metabolic route.

primary_references

[choline-p23151509] Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. (2012). https://pubmed.ncbi.nlm.nih.gov/23151509/ DOI: 10.1073/pnas.1215689109

tissue_or_cell_type

Microbial choline-utilization pathway

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1101–1112

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Anaerobic bacterial genetics, heterologous expression and EPR · source_derived_draft · unverified_draft

### choline-cutc-tma The characterized anaerobic choline-utilization pathway uses a glycyl-radical choline TMA-lyase to cleave the choline C–N bond and generate TMA. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gut microbial machinery can divert choline into a different metabolic route. organism: Desulfovibrio desulfuricans; E. coli expression host tissue_or_cell_type: Microbial choline-utilization pathway experimental_model: Anaerobic bacterial genetics, heterologous expression and EPR limitations: A bacterial enzyme pathway, not a direct human-enzyme reaction or evidence that every microbiome produces the same TMA amount. exposure: Genetic knockout and heterologous expression of choline-utilization genes evidence_span: {"source_cache": "artifacts/choline-research/23151509.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6", "start_char": 0, "end_char": 1160, "text_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6"} [choline-p23151509] Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. (2012). https://pubmed.ncbi.nlm.nih.gov/23151509/ DOI: 10.1073/pnas.1215689109

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"}

experimental_model

Controlled depletion/repletion with randomized folic acid supplementation

exposure

550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion

limitations

Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications.

nutrient_topic

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

organism

Human

plain_language

The experimentally induced signs were reversible with choline restoration.

primary_references

[choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275

tissue_or_cell_type

57 adults: 26 men, 16 premenopausal and 15 postmenopausal women

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1010–1021

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled depletion/repletion with randomized folic acid supplementation · source_derived_draft · unverified_draft

### choline-depletion-recovery Participants who developed organ dysfunction recovered normal organ function after incremental choline repletion. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The experimentally induced signs were reversible with choline restoration. organism: Human tissue_or_cell_type: 57 adults: 26 men, 16 premenopausal and 15 postmenopausal women experimental_model: Controlled depletion/repletion with randomized folic acid supplementation limitations: Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications. exposure: 550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion evidence_span: {"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"} [choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275

evidence_span

{"source_cache": "artifacts/choline-research/38693257.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3", "start_char": 0, "end_char": 1335, "text_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3"}

experimental_model

BBB expression, mouse physiology and transporter structural analysis

exposure

Flvcr2 perturbation and choline uptake

limitations

The majority-contribution result is a model result, not a universal percentage in humans. This is free-choline transport, distinct from LPC-DHA transport.

nutrient_topic

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

organism

Mouse in-vivo BBB experiments; construct-specific structural work

plain_language

Getting choline into the brain is a separate transport step from getting it into a neuron.

primary_references

[choline-p38693257] Structural and molecular basis of choline uptake into the brain by FLVCR2. (2024). https://pubmed.ncbi.nlm.nih.gov/38693257/ DOI: 10.1038/s41586-024-07326-y

tissue_or_cell_type

Blood-brain barrier endothelium

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 269–280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · BBB expression, mouse physiology and transporter structural analysis · source_derived_draft · unverified_draft

### choline-flvcr2-brain The in-vivo experiments identified Flvcr2 as a major route for blood-to-brain choline uptake. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Getting choline into the brain is a separate transport step from getting it into a neuron. organism: Mouse in-vivo BBB experiments; construct-specific structural work tissue_or_cell_type: Blood-brain barrier endothelium experimental_model: BBB expression, mouse physiology and transporter structural analysis limitations: The majority-contribution result is a model result, not a universal percentage in humans. This is free-choline transport, distinct from LPC-DHA transport. exposure: Flvcr2 perturbation and choline uptake evidence_span: {"source_cache": "artifacts/choline-research/38693257.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3", "start_char": 0, "end_char": 1335, "text_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3"} [choline-p38693257] Structural and molecular basis of choline uptake into the brain by FLVCR2. (2024). https://pubmed.ncbi.nlm.nih.gov/38693257/ DOI: 10.1038/s41586-024-07326-y

evidence_span

{"source_cache": "artifacts/choline-research/16002808.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1", "start_char": 0, "end_char": 1797, "text_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1"}

experimental_model

Randomized crossover feeding trial

exposure

About 2.6 g choline/day as PC versus matched placebo oil for two weeks; methionine-load testing

limitations

High experimental intake and biomarker endpoint; no cardiovascular-event benefit was tested.

nutrient_topic

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

organism

Human

plain_language

A choline-containing form changed a methyl-metabolism blood marker.

primary_references

[choline-p16002808] Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. (2005). https://pubmed.ncbi.nlm.nih.gov/16002808/ DOI: 10.1093/ajcn.82.1.111

tissue_or_cell_type

26 men with mildly elevated plasma homocysteine

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1075–1086

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

### choline-pc-hcy-fasting Two weeks of phosphatidylcholine supplementation reduced fasting total homocysteine by 18% relative to placebo. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A choline-containing form changed a methyl-metabolism blood marker. organism: Human tissue_or_cell_type: 26 men with mildly elevated plasma homocysteine experimental_model: Randomized crossover feeding trial limitations: High experimental intake and biomarker endpoint; no cardiovascular-event benefit was tested. exposure: About 2.6 g choline/day as PC versus matched placebo oil for two weeks; methionine-load testing evidence_span: {"source_cache": "artifacts/choline-research/16002808.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1", "start_char": 0, "end_char": 1797, "text_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1"} [choline-p16002808] Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. (2005). https://pubmed.ncbi.nlm.nih.gov/16002808/ DOI: 10.1093/ajcn.82.1.111

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}

experimental_model

Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing

exposure

Germline mouse knockout; human-cell SLC25A48 loss; labeled choline

limitations

Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.

nutrient_topic

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

organism

Human HEK293T cells

plain_language

A transport defect can restrict methyl-donor production upstream of betaine.

primary_references

[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010

tissue_or_cell_type

Brown adipose tissue and human HEK293T cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 490–501

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft

### choline-slc25a48-betaine SLC25A48 loss impaired choline-derived betaine production in human-cell mitochondrial metabolism experiments. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transport defect can restrict methyl-donor production upstream of betaine. organism: Human HEK293T cells tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010

evidence_span

{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}

experimental_model

Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing

exposure

Germline mouse knockout; human-cell SLC25A48 loss; labeled choline

limitations

Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.

nutrient_topic

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

organism

Human HEK293T cells

plain_language

Choline must cross another membrane to reach its mitochondrial metabolic route.

primary_references

[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010

tissue_or_cell_type

Brown adipose tissue and human HEK293T cells

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 477–488

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft

### choline-slc25a48-import Human-cell experiments identified SLC25A48 as necessary for efficient mitochondrial choline import. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline must cross another membrane to reach its mitochondrial metabolic route. organism: Human HEK293T cells tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010

evidence_access

Primary abstract

experimental_model

Small crossover comparisons; colloidal silica n=3, other sources at least five.

limitations

Different preparations and dissolution; not proof that choline itself suppresses absorption or defines a cofactor.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

The same elemental amount need not deliver the same soluble exposure.

primary_references

The comparative absorption of silicon from different foods and food supplements. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19356271/ · DOI 10.1017/S0007114509311757

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 80–86

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small crossover comparisons; colloidal silica n=3, other sources at least five. · source_derived_draft · unverified_draft

## silica-formulation-absorption The same elemental amount need not deliver the same soluble exposure. Urinary recovery was approximately 43% for orthosilicic acid, 17% for choline-stabilized acid and 1% for colloidal silica in this comparison. Model: Small crossover comparisons; colloidal silica n=3, other sources at least five. Limitations: Different preparations and dissolution; not proof that choline itself suppresses absorption or defines a cofactor. Evidence access: Primary abstract The comparative absorption of silicon from different foods and food supplements. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19356271/ · DOI 10.1017/S0007114509311757

evidence_access

Primary abstract

experimental_model

184 women randomized; 136 completed; all received 1,000 mg calcium and 20 micrograms D3 daily.

limitations

Marker result is not fracture prevention; attrition and multiple endpoints matter.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A collagen-formation marker changed on top of calcium and vitamin D.

primary_references

Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18547426/ · DOI 10.1186/1471-2474-9-85

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 376–382

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 184 women randomized; 136 completed; all received 1,000 mg calcium and 20 micrograms D3 daily. · source_derived_draft · unverified_draft

## silica-human-pinp A collagen-formation marker changed on top of calcium and vitamin D. PINP differed from placebo at 12 months in the 6- and 12-mg Si groups without a clear dose response. Model: 184 women randomized; 136 completed; all received 1,000 mg calcium and 20 micrograms D3 daily. Limitations: Marker result is not fracture prevention; attrition and multiple endpoints matter. Evidence access: Primary abstract Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18547426/ · DOI 10.1186/1471-2474-9-85

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human AHCY-deficiency case; different tissues and biochemical readouts.

limitations

No universal high-SAH-to-all-DNA-hypomethylation rule is inferred.

nutrient_topic

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

plain_language

A blood metabolite pattern does not predict every methylation endpoint in one direction.

primary_references

S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15024124/ · DOI 10.1073/pnas.0400658101

trigger_kind

biomarker_context Imported condition classification; unverified.

L-Methionine: transport, methylation, sulfur metabolism 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 AHCY-deficiency case; different tissues and biochemical readouts. · source_derived_draft · unverified_draft

## methionine-ahcy-methylation-boundary A blood metabolite pattern does not predict every methylation endpoint in one direction. Despite SAH accumulation, the index case showed leukocyte DNA hypermethylation, along with low plasma choline/phosphatidylcholine and high guanidinoacetate. Model: Human AHCY-deficiency case; different tissues and biochemical readouts. Limitations: No universal high-SAH-to-all-DNA-hypomethylation rule is inferred. Evidence access: Primary abstract S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15024124/ · DOI 10.1073/pnas.0400658101

experimental_model

Purified-enzyme substrate assay

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

A second phospholipid-headgroup metabolite can supply phosphate.

primary_references

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

tissue_or_cell_type

Recombinant enzyme

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested.

evidence_location

Abstract

evidence_span

declined by 50 and 75%, respectively

experimental_model

Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.

exposure

Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices

limitations

This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon.

primary_references

[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

tissue_or_cell_type

Brain slices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1112–1125

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft

### thiamine-def-stimulated-acetylcholine-synthesis The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release. evidence_location: Abstract evidence_span: declined by 50 and 75%, respectively cross_nutrient: Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested. exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

evidence_access

Primary abstract

experimental_model

Mouse hilar and stratum-radiatum interneuron recordings.

limitations

Does not mean kynurenic acid has no neural effects.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

The negative receptor result persisted with prolonged high exposure and a positive pharmacological control.

primary_references

Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 306–312

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse hilar and stratum-radiatum interneuron recordings. · source_derived_draft · unverified_draft

## tryptophan-kyna-alpha7-mouse-null The negative receptor result persisted with prolonged high exposure and a positive pharmacological control. Mouse hippocampal alpha7 currents remained insensitive to kynurenic acid, including slices prepared and stored in 1 mM for over 90 minutes, although glutamatergic currents were blocked. Model: Mouse hilar and stratum-radiatum interneuron recordings. Limitations: Does not mean kynurenic acid has no neural effects. Evidence access: Primary abstract Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108

evidence_access

Primary abstract

experimental_model

Adolescent rat stratum-radiatum interneurons in acute slices.

limitations

Slice age, temperature, agonist delivery and receptor environment are candidate explanations, not a demonstrated resolution.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

Another experiment did not reproduce the claimed receptor block.

primary_references

Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 298–304

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Adolescent rat stratum-radiatum interneurons in acute slices. · source_derived_draft · unverified_draft

## tryptophan-kyna-alpha7-rat-null Another experiment did not reproduce the claimed receptor block. Kynurenic acid did not inhibit choline-evoked alpha7 currents in rat hippocampal slice interneurons, contrasting with earlier reports. Model: Adolescent rat stratum-radiatum interneurons in acute slices. Limitations: Slice age, temperature, agonist delivery and receptor environment are candidate explanations, not a demonstrated resolution. Evidence access: Primary abstract Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108

evidence_span

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experimental_model

Choline tracer, microbial culture, microbiome transfer and atherosclerosis models

exposure

Choline-supplemented chow and berberine; deuterated choline tracing

limitations

Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.

nutrient_topic

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

organism

C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia

plain_language

The nutrient choline has a microbial metabolic branch that berberine can influence.

primary_references

[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8

tissue_or_cell_type

Microbial choline metabolism

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1078–1089

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft

### berberine-choline-tma Berberine inhibited choline-to-TMA conversion in bacterial cultures and gut consortia, including human fecal samples. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nutrient choline has a microbial metabolic branch that berberine can influence. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8

acting_entity

s-allylcysteine

availability_state

nutrient_deficiency Imported condition classification; unverified.

dose

SAC 1 g/L drinking water

duration

Seven weeks

evidence_access

Primary abstract

experimental_comparison

SAC or S-ethylcysteine separately with deficient diet versus diet controls

experimental_model

Methionine/choline-deficient diet; liver and serum measurements

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Does not establish replacement of methionine or choline, or direct donation of cysteine to GSH.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Mus musculus

plain_language

A nutrient-deficiency model connects SAC to glutathione status.

primary_references

[18786595] Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18786595/ · DOI 10.1016/j.fct.2008.08.010

route

Oral drinking water

tissue_or_cell_type

Methionine/choline-deficient diet; liver and serum measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 365–372

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Methionine/choline-deficient diet; liver and serum measurements · source_derived_draft · unverified_draft

## s-allylcysteine-mcd-glutathione A nutrient-deficiency model connects SAC to glutathione status. SAC in drinking water increased serum and hepatic GSH during methionine/choline-deficient feeding. Model: Methionine/choline-deficient diet; liver and serum measurements Limitations: Does not establish replacement of methionine or choline, or direct donation of cysteine to GSH. Evidence access: Primary abstract [18786595] Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18786595/ · DOI 10.1016/j.fct.2008.08.010 Structured context: {"organism": "Mus musculus", "tissue_or_cell_type": "Methionine/choline-deficient diet; liver and serum measurements", "dose": "SAC 1 g/L drinking water", "duration": "Seven weeks", "route": "Oral drinking water", "experimental_comparison": "SAC or S-ethylcysteine separately with deficient diet versus diet controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

acting_entity

s-allylcysteine

availability_state

nutrient_deficiency Imported condition classification; unverified.

dose

SAC 1 g/L drinking water

duration

Seven weeks

evidence_access

Primary abstract

experimental_comparison

SAC or S-ethylcysteine separately with deficient diet versus diet controls

experimental_model

Methionine/choline-deficient diet; liver and serum measurements

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Model-specific enzyme activities; not evidence of direct G6PDH binding or a universal NADPH effect.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Mus musculus

plain_language

The response involved lipid metabolism as well as redox markers.

primary_references

[18786595] Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18786595/ · DOI 10.1016/j.fct.2008.08.010

route

Oral drinking water

tissue_or_cell_type

Methionine/choline-deficient diet; liver and serum measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 374–381

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Methionine/choline-deficient diet; liver and serum measurements · source_derived_draft · unverified_draft

## s-allylcysteine-mcd-lipogenesis The response involved lipid metabolism as well as redox markers. SAC reduced hepatic G6PDH and FAS activities and triglyceride accumulation during the deficient diet. Model: Methionine/choline-deficient diet; liver and serum measurements Limitations: Model-specific enzyme activities; not evidence of direct G6PDH binding or a universal NADPH effect. Evidence access: Primary abstract [18786595] Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18786595/ · DOI 10.1016/j.fct.2008.08.010 Structured context: {"organism": "Mus musculus", "tissue_or_cell_type": "Methionine/choline-deficient diet; liver and serum measurements", "dose": "SAC 1 g/L drinking water", "duration": "Seven weeks", "route": "Oral drinking water", "experimental_comparison": "SAC or S-ethylcysteine separately with deficient diet versus diet controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Folate-pathway genotype relates to choline allocation.

experimental_model

Choline feeding and isotope tracing in women across reproductive states.

limitations

Genotypes not randomized; ratio is a pathway proxy.

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

Relative choline allocation shifted toward phosphatidylcholine.

primary_references

[ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr

tissue_or_cell_type

Plasma tracer metabolites

trigger_kind

machinery_impairment Imported condition classification; unverified.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–741

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline feeding and isotope tracing in women across reproductive states. · source_derived_draft · unverified_draft

### folate-methyl-variant-choline-allocation Nonpregnant MTHFR rs1801133 carriers had lower labeled betaine:phosphatidylcholine enrichment ratios than noncarriers (0.8 versus 0.9). Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Relative choline allocation shifted toward phosphatidylcholine. organism: Homo sapiens tissue_or_cell_type: Plasma tracer metabolites experimental_model: Choline feeding and isotope tracing in women across reproductive states. limitations: Genotypes not randomized; ratio is a pathway proxy. cross_nutrient: Folate-pathway genotype relates to choline allocation. [ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr