Component

Betaine

Trimethylglycine, a substrate of BHMT.

7 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

Where it participates (unsigned role)

  1. Purified recombinant human ALDH7A1 metabolized betaine aldehyde.

    Antiquitin / ALDH7A1 → Betaine aldehyde source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/20207735.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5", "start_char": 0, "end_char": 1582, "text_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5"}
    experimental_model
    Purified recombinant human enzyme and CHO-cell expression
    exposure
    Betaine aldehyde substrate; increased extracellular sucrose or NaCl
    limitations
    ALDH7A1 accepts several aldehydes. Cell protection was not proved to be mediated exclusively by betaine or to predict benefit in pyridoxine-dependent epilepsy.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human ALDH7A1; Chinese hamster ovary expression host
    plain_language
    The lysine-pathway enzyme already in the ledger also has activity on a choline-derived aldehyde.
    primary_references
    [choline-p20207735] Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. (2010). https://pubmed.ncbi.nlm.nih.gov/20207735/ DOI: 10.1074/jbc.m109.077925
    tissue_or_cell_type
    Purified enzyme and osmotic-stress cell assays

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 633–644

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

    ### choline-aldh7-betaine Purified recombinant human ALDH7A1 metabolized betaine aldehyde. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The lysine-pathway enzyme already in the ledger also has activity on a choline-derived aldehyde. organism: Human ALDH7A1; Chinese hamster ovary expression host tissue_or_cell_type: Purified enzyme and osmotic-stress cell assays experimental_model: Purified recombinant human enzyme and CHO-cell expression limitations: ALDH7A1 accepts several aldehydes. Cell protection was not proved to be mediated exclusively by betaine or to predict benefit in pyridoxine-dependent epilepsy. exposure: Betaine aldehyde substrate; increased extracellular sucrose or NaCl evidence_span: {"source_cache": "artifacts/choline-research/20207735.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5", "start_char": 0, "end_char": 1582, "text_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5"} [choline-p20207735] Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. (2010). https://pubmed.ncbi.nlm.nih.gov/20207735/ DOI: 10.1074/jbc.m109.077925
    Complete structured claim and evidence

  2. Purified human E3 aldehyde dehydrogenase showed betaine-aldehyde dehydrogenase activity, with the activities co-purifying across six columns.

    ALDH9A1 → Betaine aldehyde source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/7646513.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc", "start_char": 0, "end_char": 687, "text_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc"}
    experimental_model
    Purified human E3 aldehyde dehydrogenase substrate assays
    exposure
    Betaine aldehyde and 4-aminobutyraldehyde activity across six chromatography steps
    limitations
    E3/ALDH9A1 has demonstrated betaine-aldehyde activity; not an exclusive assignment of every tissue’s betaine synthesis to this enzyme.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human enzyme
    plain_language
    This enzyme can process the aldehyde intermediate in the betaine pathway.
    primary_references
    [choline-p7646513] Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase. (1995). https://pubmed.ncbi.nlm.nih.gov/7646513/ DOI: 10.1006/bbrc.1995.2168
    tissue_or_cell_type
    Purified protein

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 607–618

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human E3 aldehyde dehydrogenase substrate assays · source_derived_draft · unverified_draft

    ### choline-aldh9-betaine Purified human E3 aldehyde dehydrogenase showed betaine-aldehyde dehydrogenase activity, with the activities co-purifying across six columns. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme can process the aldehyde intermediate in the betaine pathway. organism: Human enzyme tissue_or_cell_type: Purified protein experimental_model: Purified human E3 aldehyde dehydrogenase substrate assays limitations: E3/ALDH9A1 has demonstrated betaine-aldehyde activity; not an exclusive assignment of every tissue’s betaine synthesis to this enzyme. exposure: Betaine aldehyde and 4-aminobutyraldehyde activity across six chromatography steps evidence_span: {"source_cache": "artifacts/choline-research/7646513.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc", "start_char": 0, "end_char": 687, "text_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc"} [choline-p7646513] Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase. (1995). https://pubmed.ncbi.nlm.nih.gov/7646513/ DOI: 10.1006/bbrc.1995.2168
    Complete structured claim and evidence

  3. SLC25A48 loss impaired choline-derived betaine production in human-cell mitochondrial metabolism experiments.

    SLC25A48-deficient human cells in the 2024 transport studies → Human mitochondrial choline-derived betaine synthesis source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

  4. Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction.

    Betaine-homocysteine S-methyltransferase / BHMT → L-Methionine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Betaine/choline and folate routes meet at homocysteine.
    experimental_model
    Recombinant human BHMT and human liver-derived BHMT.
    limitations
    Does not establish complete folate substitution in vivo.
    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
    Betaine supplies another recycling route.
    primary_references
    [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
    tissue_or_cell_type
    Recombinant and liver-derived enzyme

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 610–620

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

    ### folate-methyl-bhmt-reaction Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Betaine supplies another recycling route. organism: Homo sapiens tissue_or_cell_type: Recombinant and liver-derived enzyme experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Does not establish complete folate substitution in vivo. cross_nutrient: Betaine/choline and folate routes meet at homocysteine. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
    Complete structured claim and evidence

  5. Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content.

    Zinc(II) ion → Betaine-homocysteine S-methyltransferase / BHMT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Zinc supports parallel remethylation.
    experimental_model
    Recombinant human BHMT and human liver-derived BHMT.
    limitations
    Demetallation is not dietary zinc deficiency.
    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 betaine route requires a zinc-containing enzyme.
    primary_references
    [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
    tissue_or_cell_type
    Purified protein

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–632

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

    ### folate-methyl-bhmt-zinc Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The betaine route requires a zinc-containing enzyme. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Demetallation is not dietary zinc deficiency. cross_nutrient: Zinc supports parallel remethylation. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
    Complete structured claim and evidence

  6. Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice.

    Folic acid → Homocysteine source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Folate/betaine compensation has limits.
    experimental_model
    Bhmt-null and wild-type mice; four-week folate feeding.
    exposure
    0, 2 or 20 mg folate/kg diet
    limitations
    Mouse four-week experiment, not a human treatment rule.
    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
    Extra folate did not restore this missing route.
    primary_references
    [teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
    tissue_or_cell_type
    Plasma
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 668–679

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

    ### folate-methyl-folate-no-hcy-rescue-bhmt Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra folate did not restore this missing route. organism: Mus musculus tissue_or_cell_type: Plasma experimental_model: Bhmt-null and wild-type mice; four-week folate feeding. limitations: Mouse four-week experiment, not a human treatment rule. exposure: 0, 2 or 20 mg folate/kg diet cross_nutrient: Folate/betaine compensation has limits. [teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
    Complete structured claim and evidence

  7. Nonpregnant MTHFR rs1801133 carriers had lower labeled betaine:phosphatidylcholine enrichment ratios than noncarriers (0.8 versus 0.9).

    MTHFR Ala222Val protein → Choline partitioning between betaine and phosphatidylcholine source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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