S-Adenosyl-L-homocysteine

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/16081510.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e93fafd7946f8a4aea30ff3ee9ef05e303f9154eb947410fca8e63c6521a4170", "start_char": 0, "end_char": 2008, "text_sha256": "e93fafd7946f8a4aea30ff3ee9ef05e303f9154eb947410fca8e63c6521a4170"}

experimental_model

Coupled catechol-methylation/DNA-methylation assays and breast-cancer cell experiments

exposure

CGA DNMT1 IC50 0.9 micromolar in the coupled assay; compounds tested up to 20 micromolar

limitations

These concentrations and coupled-reaction conditions do not establish whole-body methyl-donor depletion, anticancer benefit or vitamin deficiency after food intake. COMT-mediated SAH generation is distinct from direct competitive binding to DNMT1.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human DNMT1 and MCF-7/MDA-MB-231 cells; COMT preparation species unresolved in abstract

plain_language

An indirect metabolite-mediated effect differs from a direct DNMT1 inhibitor.

primary_references

[chlorogenic_acid-p16081510] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. (2006). https://pubmed.ncbi.nlm.nih.gov/16081510/ DOI: 10.1093/carcin/bgi206

tissue_or_cell_type

Cell-free methyltransferase reactions and cultured cancer cells

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 802–813

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coupled catechol-methylation/DNA-methylation assays and breast-cancer cell experiments · source_derived_draft · unverified_draft

### chlorogenic_acid-sah-dnmt Increased SAH largely explained the observed inhibition of DNA methylation. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An indirect metabolite-mediated effect differs from a direct DNMT1 inhibitor. organism: Human DNMT1 and MCF-7/MDA-MB-231 cells; COMT preparation species unresolved in abstract tissue_or_cell_type: Cell-free methyltransferase reactions and cultured cancer cells experimental_model: Coupled catechol-methylation/DNA-methylation assays and breast-cancer cell experiments limitations: These concentrations and coupled-reaction conditions do not establish whole-body methyl-donor depletion, anticancer benefit or vitamin deficiency after food intake. COMT-mediated SAH generation is distinct from direct competitive binding to DNMT1. exposure: CGA DNMT1 IC50 0.9 micromolar in the coupled assay; compounds tested up to 20 micromolar evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/16081510.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e93fafd7946f8a4aea30ff3ee9ef05e303f9154eb947410fca8e63c6521a4170", "start_char": 0, "end_char": 2008, "text_sha256": "e93fafd7946f8a4aea30ff3ee9ef05e303f9154eb947410fca8e63c6521a4170"} [chlorogenic_acid-p16081510] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. (2006). https://pubmed.ncbi.nlm.nih.gov/16081510/ DOI: 10.1093/carcin/bgi206

experimental_model

Recombinant human MTHFR; cryo-EM and biochemistry.

limitations

Does not imply SAH promotes all methyltransferases.

nutrient_topic

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

organism

Homo sapiens

plain_language

The SAH-bound structure leaves the catalytic site accessible.

primary_references

[mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y

tissue_or_cell_type

Purified protein

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 471–480

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR; cryo-EM and biochemistry. · source_derived_draft · unverified_draft

### folate-methyl-sah-active-state Single SAH occupancy accompanied a flexible catalytic domain with an exposed active site in human MTHFR structures. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The SAH-bound structure leaves the catalytic site accessible. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human MTHFR; cryo-EM and biochemistry. limitations: Does not imply SAH promotes all methyltransferases. [mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y

evidence_span

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experimental_model

Coupled catechol-methylation/DNA-methylation assays and breast-cancer cell experiments

exposure

CGA DNMT1 IC50 0.9 micromolar in the coupled assay; compounds tested up to 20 micromolar

limitations

These concentrations and coupled-reaction conditions do not establish whole-body methyl-donor depletion, anticancer benefit or vitamin deficiency after food intake. COMT-mediated SAH generation is distinct from direct competitive binding to DNMT1.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human DNMT1 and MCF-7/MDA-MB-231 cells; COMT preparation species unresolved in abstract

plain_language

Using a methyl donor leaves a product that can restrain other methyltransferases.

primary_references

[chlorogenic_acid-p16081510] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. (2006). https://pubmed.ncbi.nlm.nih.gov/16081510/ DOI: 10.1093/carcin/bgi206

tissue_or_cell_type

Cell-free methyltransferase reactions and cultured cancer cells

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 789–800

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coupled catechol-methylation/DNA-methylation assays and breast-cancer cell experiments · source_derived_draft · unverified_draft

### chlorogenic_acid-comt-sah O-methylation of the dietary catechols increased SAH formation. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Using a methyl donor leaves a product that can restrain other methyltransferases. organism: Human DNMT1 and MCF-7/MDA-MB-231 cells; COMT preparation species unresolved in abstract tissue_or_cell_type: Cell-free methyltransferase reactions and cultured cancer cells experimental_model: Coupled catechol-methylation/DNA-methylation assays and breast-cancer cell experiments limitations: These concentrations and coupled-reaction conditions do not establish whole-body methyl-donor depletion, anticancer benefit or vitamin deficiency after food intake. COMT-mediated SAH generation is distinct from direct competitive binding to DNMT1. exposure: CGA DNMT1 IC50 0.9 micromolar in the coupled assay; compounds tested up to 20 micromolar evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/16081510.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e93fafd7946f8a4aea30ff3ee9ef05e303f9154eb947410fca8e63c6521a4170", "start_char": 0, "end_char": 2008, "text_sha256": "e93fafd7946f8a4aea30ff3ee9ef05e303f9154eb947410fca8e63c6521a4170"} [chlorogenic_acid-p16081510] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. (2006). https://pubmed.ncbi.nlm.nih.gov/16081510/ DOI: 10.1093/carcin/bgi206

evidence_access

Primary abstract

experimental_model

Established reaction in the human AHCY-deficiency investigation.

limitations

Reaction equilibrium and cellular product removal matter; plasma concentrations do not uniquely define tissue flux.

nutrient_topic

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

plain_language

After methyl transfer, the spent donor must be processed.

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

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 172–178

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established reaction in the human AHCY-deficiency investigation. · source_derived_draft · unverified_draft

## methionine-ahcy-reaction After methyl transfer, the spent donor must be processed. AHCY catalyzes reversible conversion between SAH and adenosine plus homocysteine; product clearance favors net SAH removal. Model: Established reaction in the human AHCY-deficiency investigation. Limitations: Reaction equilibrium and cellular product removal matter; plasma concentrations do not uniquely define tissue flux. 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

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Bhmt-null mice and wild-type controls.

limitations

No direct epigenetic inference.

nutrient_topic

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

organism

Mus musculus

plain_language

The spent methyl-donor pool increased.

primary_references

[teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348

tissue_or_cell_type

Liver

trigger_kind

machinery_impairment Imported condition classification; unverified.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 657–666

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null mice and wild-type controls. · source_derived_draft · unverified_draft

### folate-methyl-bhmt-ko-sah Bhmt-null mouse liver contained about threefold more SAH than wild type. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The spent methyl-donor pool increased. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Bhmt-null mice and wild-type controls. limitations: No direct epigenetic inference. [teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348

evidence_span

{"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"}

experimental_model

X-ray structure and radioenzymatic variant characterization

exposure

SAM-dependent methyltransferase structure and enzyme activity assays

limitations

Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome.

nutrient_topic

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

organism

Human ASMT and 20 nonsynonymous variants

plain_language

A methyl group completes the molecule.

primary_references

[melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x

tissue_or_cell_type

Final melatonin synthesis step

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 201–212

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure and radioenzymatic variant characterization · source_derived_draft · unverified_draft

### melatonin-asmt-methylation Human ASMT catalyzes the terminal methylation step converting N-acetylserotonin to melatonin using SAM. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A methyl group completes the molecule. organism: Human ASMT and 20 nonsynonymous variants tissue_or_cell_type: Final melatonin synthesis step experimental_model: X-ray structure and radioenzymatic variant characterization limitations: Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome. exposure: SAM-dependent methyltransferase structure and enzyme activity assays evidence_span: {"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"} [melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Six affected individuals from three families; exome sequencing and recombinant variant assays.

limitations

A functional block of SAH hydrolysis from adenosine accumulation is the mechanistic interpretation; this is not primary AHCY deficiency.

nutrient_topic

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

plain_language

Removing one reaction product helps keep the recycling pathway moving.

primary_references

Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21963049/ · DOI 10.1016/j.ajhg.2011.09.004

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Methionine: transport, methylation, sulfur metabolism 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 · Six affected individuals from three families; exome sequencing and recombinant variant assays. · source_derived_draft · unverified_draft

## methionine-adk-product-removal Removing one reaction product helps keep the recycling pathway moving. ADK variants impaired recombinant enzyme activity and were linked to increased adenosine excretion and SAM/SAH/methionine accumulation. Model: Six affected individuals from three families; exome sequencing and recombinant variant assays. Limitations: A functional block of SAH hydrolysis from adenosine accumulation is the mechanistic interpretation; this is not primary AHCY deficiency. Evidence access: Primary abstract Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21963049/ · DOI 10.1016/j.ajhg.2011.09.004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human infant, liver/red-cell/fibroblast assays and genetic analysis.

limitations

Single rare-disease case; not evidence of the same block in ordinary dietary variation.

nutrient_topic

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

plain_language

Abundant methyl-donor substrate can coexist with blocked recycling.

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

machinery_impairment Imported condition classification; unverified.

L-Methionine: transport, methylation, sulfur metabolism 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 infant, liver/red-cell/fibroblast assays and genetic analysis. · source_derived_draft · unverified_draft

## methionine-ahcy-loss Abundant methyl-donor substrate can coexist with blocked recycling. The index AHCY-deficient patient had very low enzyme activity and markedly elevated plasma SAH, SAM and methionine. Model: Human infant, liver/red-cell/fibroblast assays and genetic analysis. Limitations: Single rare-disease case; not evidence of the same block in ordinary dietary variation. 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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and primary figure legends

experimental_model

Human HCT116 and additional cultured-cell experiments; restriction/recovery.

limitations

H3K4me3 is not interchangeable with DNA methylation or all histone marks.

nutrient_topic

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

plain_language

Availability changed a specific chromatin mark, reversibly.

primary_references

Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26411344/ · DOI 10.1016/j.cmet.2015.08.024

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 276–282

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HCT116 and additional cultured-cell experiments; restriction/recovery. · source_derived_draft · unverified_draft

## methionine-histone-response Availability changed a specific chromatin mark, reversibly. Methionine restriction changed SAM/SAH pools and rapidly reduced H3K4me3; restoring methionine restored the metabolic and methylation response. Model: Human HCT116 and additional cultured-cell experiments; restriction/recovery. Limitations: H3K4me3 is not interchangeable with DNA methylation or all histone marks. Evidence access: Primary abstract and primary figure legends Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26411344/ · DOI 10.1016/j.cmet.2015.08.024

evidence_span

{"source_cache": "artifacts/creatine-research/12079381.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6", "start_char": 0, "end_char": 1161, "text_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6"}

experimental_model

SAH-bound crystal structure and mutagenesis

exposure

SAH-bound structure at 2.5 angstrom resolution

limitations

The crystallized construct lacks 36 N-terminal residues; its dimer arrangement is not assigned universally to native human GAMT.

nutrient_topic

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

organism

Rat GAMT

plain_language

The second synthesis step spends one SAM methyl group to finish each creatine molecule.

primary_references

[creatine-p12079381] Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12079381/ DOI: 10.1016/s0022-2836(02)00448-5 [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095

tissue_or_cell_type

Purified, N-terminally truncated enzyme

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 203–215

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

### creatine-gamt-methyl-transfer GAMT transfers a methyl group from S-adenosylmethionine to guanidinoacetate, producing creatine and S-adenosylhomocysteine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second synthesis step spends one SAM methyl group to finish each creatine molecule. organism: Rat GAMT tissue_or_cell_type: Purified, N-terminally truncated enzyme experimental_model: SAH-bound crystal structure and mutagenesis limitations: The crystallized construct lacks 36 N-terminal residues; its dimer arrangement is not assigned universally to native human GAMT. exposure: SAH-bound structure at 2.5 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12079381.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6", "start_char": 0, "end_char": 1161, "text_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6"} [creatine-p12079381] Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12079381/ DOI: 10.1016/s0022-2836(02)00448-5 [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers.

experimental_model

Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo.

exposure

1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial.

limitations

Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP.

nutrient_topic

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

organism

Homo sapiens

plain_language

B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.

primary_references

[b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004

tissue_or_cell_type

Human clinical setting

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1514–1525

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo. · source_derived_draft · unverified_draft

### b2-tt-plasma-sam-response In the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo. limitations: Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP. exposure: 1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial. cross_nutrient: B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers. [b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004

evidence_access

Primary abstract

experimental_model

Apo and ligand-bound enzyme structures.

limitations

No evidence that human ergothioneine consumption drains SAM; humans lack this established synthesis pathway.

nutrient_topic

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

plain_language

The microbial synthesis branch connects to methyl-donor chemistry.

primary_references

Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25251321/ · DOI 10.1016/j.bbrc.2014.09.058

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 552–558

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

## ergothioneine-egtd-sam The microbial synthesis branch connects to methyl-donor chemistry. Mycobacterium smegmatis EgtD uses SAM-dependent methyl transfer to convert histidine into hercynine. Model: Apo and ligand-bound enzyme structures. Limitations: No evidence that human ergothioneine consumption drains SAM; humans lack this established synthesis pathway. Evidence access: Primary abstract Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25251321/ · DOI 10.1016/j.bbrc.2014.09.058

evidence_access

Primary abstract

experimental_model

Purified recombinant human enzyme; ternary structures and steady-state kinetics.

limitations

A shared SAM requirement does not prove clinically important methyl depletion from histamine turnover.

nutrient_topic

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

plain_language

Histamine disposal connects to the cellular methyl-donor system.

primary_references

Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11566133/ · DOI 10.1016/s0969-2126(01)00643-8

L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 210–216

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

## histidine-hnmt-methylation Histamine disposal connects to the cellular methyl-donor system. Human HNMT methylates histamine using SAM; structural complexes locate histamine and the reaction product SAH at the enzyme. Model: Purified recombinant human enzyme; ternary structures and steady-state kinetics. Limitations: A shared SAM requirement does not prove clinically important methyl depletion from histamine turnover. Evidence access: Primary abstract Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11566133/ · DOI 10.1016/s0969-2126(01)00643-8

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 35", "start_char": 19327, "end_char": 21089, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "5b6ea17ec741ecc064f97de9d83d49809db5e62588ffc1164e6e771fc9fc50c3"}

experimental_model

Immunoblotting of histone methylation in engineered cells

exposure

NNMT overexpression; 10 or 20 micromolar methionine; GFP and inactive NNMT controls

limitations

Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. Not every histone mark changed; this does not establish global DNA hypomethylation.

nutrient_topic

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

organism

Human

plain_language

NNMT changed several histone methylation marks in this culture model.

primary_references

[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

tissue_or_cell_type

Human 769P renal carcinoma cells

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 803–815

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunoblotting of histone methylation in engineered cells · source_derived_draft · unverified_draft

### b3-cons-nnmt-histone-methylation At 10–20 micromolar medium methionine, NNMT-overexpressing 769P cells had reduced methylation of several histone lysine marks compared with controls. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NNMT changed several histone methylation marks in this culture model. organism: Human tissue_or_cell_type: Human 769P renal carcinoma cells experimental_model: Immunoblotting of histone methylation in engineered cells limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. Not every histone mark changed; this does not establish global DNA hypomethylation. exposure: NNMT overexpression; 10 or 20 micromolar methionine; GFP and inactive NNMT controls cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 35", "start_char": 19327, "end_char": 21089, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "5b6ea17ec741ecc064f97de9d83d49809db5e62588ffc1164e6e771fc9fc50c3"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 8", "start_char": 2396, "end_char": 4508, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "fc5cdd48751fa59656f5c16e70c31ab3f36788c265267d7cb57f269bb1848fc6"}

experimental_model

Human cancer-cell enzyme activity and metabolomics study

exposure

Nicotinamide substrate and NNMT expression/activity comparisons

limitations

Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements.

nutrient_topic

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

organism

Human

plain_language

Nicotinamide methylation uses a methyl group from SAM.

primary_references

[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

tissue_or_cell_type

769P, OVCAR3, MUM2C and comparison cell models

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 747–759

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

### b3-cons-nnmt-methyl-transfer NNMT transfers a methyl group from SAM to nicotinamide, yielding N1-methylnicotinamide and S-adenosylhomocysteine. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinamide methylation uses a methyl group from SAM. organism: Human tissue_or_cell_type: 769P, OVCAR3, MUM2C and comparison cell models experimental_model: Human cancer-cell enzyme activity and metabolomics study limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. exposure: Nicotinamide substrate and NNMT expression/activity comparisons cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 8", "start_char": 2396, "end_char": 4508, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "fc5cdd48751fa59656f5c16e70c31ab3f36788c265267d7cb57f269bb1848fc6"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"}

experimental_model

Targeted LC-MS metabolomics

exposure

Stable NNMT overexpression; 100 micromolar methionine medium and lower-methionine comparisons

limitations

Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements.

nutrient_topic

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

organism

Human

plain_language

Extra NNMT activity increased the methyl-transfer coproduct SAH.

primary_references

[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

tissue_or_cell_type

769P renal carcinoma; MUM2C and OVCAR3 comparisons

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 761–773

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

### b3-cons-nnmt-sah-increase NNMT overexpression raised cellular SAH relative to GFP or inactive-NNMT controls in the tested human cancer-cell models. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra NNMT activity increased the methyl-transfer coproduct SAH. organism: Human tissue_or_cell_type: 769P renal carcinoma; MUM2C and OVCAR3 comparisons experimental_model: Targeted LC-MS metabolomics limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. exposure: Stable NNMT overexpression; 100 micromolar methionine medium and lower-methionine comparisons cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"}

experimental_model

Targeted LC-MS metabolomics

exposure

100 micromolar methionine culture medium; NNMT overexpression

limitations

Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements.

nutrient_topic

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

organism

Human

plain_language

A higher methyl-transfer product did not necessarily mean a large fall in SAM.

primary_references

[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

tissue_or_cell_type

Human cancer-cell overexpression models

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 775–787

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

### b3-cons-nnmt-sam-standard At standard 100 micromolar medium methionine, NNMT overexpression changed SAM by less than 1.5-fold despite increased SAH. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher methyl-transfer product did not necessarily mean a large fall in SAM. organism: Human tissue_or_cell_type: Human cancer-cell overexpression models experimental_model: Targeted LC-MS metabolomics limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. exposure: 100 micromolar methionine culture medium; NNMT overexpression cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204

evidence_access

Primary abstract plus Reactome reaction R-HSA-8876789

experimental_model

Purified human enzyme; reaction identity also curated in Reactome R-HSA-8876789.

limitations

Does not establish methyl-donor depletion or benefit from folate/B12 supplements.

nutrient_topic

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

plain_language

A methyl group turns carnosine into a distinct peptide.

primary_references

UPF0586 Protein C9orf41 Homolog Is Anserine-producing Methyltransferase. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26001783/ · DOI 10.1074/jbc.M115.640037

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 148–154

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; reaction identity also curated in Reactome R-HSA-8876789. · source_derived_draft · unverified_draft

## carnosine-methylation A methyl group turns carnosine into a distinct peptide. Recombinant human CARNMT1 methylated carnosine to anserine; the reaction uses S-adenosylmethionine as methyl donor. Model: Purified human enzyme; reaction identity also curated in Reactome R-HSA-8876789. Limitations: Does not establish methyl-donor depletion or benefit from folate/B12 supplements. Evidence access: Primary abstract plus Reactome reaction R-HSA-8876789 UPF0586 Protein C9orf41 Homolog Is Anserine-producing Methyltransferase. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26001783/ · DOI 10.1074/jbc.M115.640037

experimental_model

Purified human SET7/9 structure and H3-peptide assays.

limitations

Peptide activity does not establish SETD7 as the dominant H3K4 writer in every chromatin context. 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

SAM provides the methyl group; the protein-bound lysine receives it.

primary_references

[setd7-2002] Crystal structure and functional analysis of the histone methyltransferase SET7/9 (2002). https://pubmed.ncbi.nlm.nih.gov/12372304/ DOI: 10.1016/s0092-8674(02)00964-9

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 547–555

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SET7/9 structure and H3-peptide assays. · source_derived_draft · unverified_draft

### setd7-h3k4-methylation SETD7 transfers a methyl group from SAM to histone H3 Lys4 in peptide assays. Plain language: SAM provides the methyl group; the protein-bound lysine receives it. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified human SET7/9 structure and H3-peptide assays. limitations: Peptide activity does not establish SETD7 as the dominant H3K4 writer in every chromatin context. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [setd7-2002] Crystal structure and functional analysis of the histone methyltransferase SET7/9 (2002). https://pubmed.ncbi.nlm.nih.gov/12372304/ DOI: 10.1016/s0092-8674(02)00964-9

experimental_model

Native rat liver and bacterially expressed rat GNMT.

limitations

Does not quantify whole-body methyl demand.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

GNMT spends a SAM methyl group on glycine.

primary_references

[luka-2008] Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate (2008). https://pubmed.ncbi.nlm.nih.gov/18501206/ DOI: 10.1016/j.bbapap.2008.04.016

tissue_or_cell_type

Native/recombinant rat enzyme

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 756–765

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Native rat liver and bacterially expressed rat GNMT. · source_derived_draft · unverified_draft

### folate-methyl-gnmt-methyl-use Rat GNMT activity assays measured SAM-dependent glycine methylation to sarcosine. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: GNMT spends a SAM methyl group on glycine. organism: Rattus norvegicus tissue_or_cell_type: Native/recombinant rat enzyme experimental_model: Native rat liver and bacterially expressed rat GNMT. limitations: Does not quantify whole-body methyl demand. [luka-2008] Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate (2008). https://pubmed.ncbi.nlm.nih.gov/18501206/ DOI: 10.1016/j.bbapap.2008.04.016

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Mtrr gene-trap hypomorphic mice and controls.

limitations

Ratio is not DNA methylation.

nutrient_topic

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

organism

Mus musculus

plain_language

The ratio did not fall uniformly.

primary_references

[elmore-2007] Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase (2007). https://pubmed.ncbi.nlm.nih.gov/17369066/ DOI: 10.1016/j.ymgme.2007.02.001

tissue_or_cell_type

Assayed tissue panel

trigger_kind

machinery_impairment Imported condition classification; unverified.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 588–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mtrr gene-trap hypomorphic mice and controls. · source_derived_draft · unverified_draft

### folate-methyl-mtrr-mouse-ratio Mtrr gene-trap mice did not show decreased SAM:SAH ratios in most tissues despite disturbed remethylation. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ratio did not fall uniformly. organism: Mus musculus tissue_or_cell_type: Assayed tissue panel experimental_model: Mtrr gene-trap hypomorphic mice and controls. limitations: Ratio is not DNA methylation. [elmore-2007] Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase (2007). https://pubmed.ncbi.nlm.nih.gov/17369066/ DOI: 10.1016/j.ymgme.2007.02.001