Component

Free N-epsilon-trimethyl-L-lysine

Independent small molecule record; interpretation is limited by each linked claim and its study context.

4 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

What it acts on

  1. Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.

    Free N-epsilon-trimethyl-L-lysine → (2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays
    limitations
    The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.
    organism
    Homo sapiens
    plain_language
    TMLHE begins conversion of released trimethyllysine toward carnitine.
    primary_references
    [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A
    tissue_or_cell_type
    Mitochondrial carnitine-biosynthesis step

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 166–175

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays · source_derived_draft · unverified_draft

    ### tmlhe-hydroxylation Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation. Plain language: TMLHE begins conversion of released trimethyllysine toward carnitine. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial carnitine-biosynthesis step experimental_model: Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays limitations: The substrate is free trimethyllysine after proteolysis, not ordinary free lysine. [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A
    Complete structured claim and evidence

  2. Oral trimethyllysine increased urine-based estimated carnitine synthesis by 32–40 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response.

    Free N-epsilon-trimethyl-L-lysine → Guinea-pig carnitine synthesis estimated from urinary output source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    cross_nutrient
    Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
    experimental_model
    Guinea-pig dietary deficiency with pair feeding and precursor loading
    exposure
    Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls.
    limitations
    Estimate is derived from excretion during a large precursor load, not isotope-resolved basal flux; does not show all tissues are vitamin-C-independent.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Cavia porcellus
    plain_language
    Even vitamin-C-deficient animals could make substantial carnitine when given this precursor.
    primary_references
    [carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
    tissue_or_cell_type
    Whole animal; urine-based synthesis estimate
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 754–765

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Guinea-pig dietary deficiency with pair feeding and precursor loading · source_derived_draft · unverified_draft

    ### vc-enzyme-deficient-tml-response Oral trimethyllysine increased urine-based estimated carnitine synthesis by 32–40 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even vitamin-C-deficient animals could make substantial carnitine when given this precursor. organism: Cavia porcellus tissue_or_cell_type: Whole animal; urine-based synthesis estimate experimental_model: Guinea-pig dietary deficiency with pair feeding and precursor loading limitations: Estimate is derived from excretion during a large precursor load, not isotope-resolved basal flux; does not show all tissues are vitamin-C-independent. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls. [carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
    Complete structured claim and evidence

What acts on it

  1. Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis.

    Protein-bound N-epsilon-trimethyllysine residues → Free N-epsilon-trimethyl-L-lysine source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Radiolabeled asialofetuin metabolism in rats and perfused rat liver
    limitations
    Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge.
    organism
    Rattus norvegicus
    plain_language
    Protein breakdown releases the modified lysine used to make carnitine.
    primary_references
    [labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
    tissue_or_cell_type
    Liver lysosomes and downstream metabolism

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 156–164

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled asialofetuin metabolism in rats and perfused rat liver · source_derived_draft · unverified_draft

    ### protein-tml-release Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis. Plain language: Protein breakdown releases the modified lysine used to make carnitine. Condition category: normal organism: Rattus norvegicus tissue_or_cell_type: Liver lysosomes and downstream metabolism experimental_model: Radiolabeled asialofetuin metabolism in rats and perfused rat liver limitations: Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge. [labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine.

    L-Ascorbate → Trimethyllysine hydroxylase / TMLHE source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+.
    experimental_model
    Recombinant human MBP-TMLH-a; mass spectrometry and NMR
    exposure
    500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls.
    limitations
    New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Homo sapiens
    plain_language
    The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate.
    primary_references
    [tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a
    tissue_or_cell_type
    Cell-free recombinant enzyme

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 689–700

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MBP-TMLH-a; mass spectrometry and NMR · source_derived_draft · unverified_draft

    ### vc-enzyme-tmlh-ascorbate-dependency Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate. organism: Homo sapiens tissue_or_cell_type: Cell-free recombinant enzyme experimental_model: Recombinant human MBP-TMLH-a; mass spectrometry and NMR limitations: New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux. cross_nutrient: Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+. exposure: 500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls. [tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a
    Complete structured claim and evidence

In the sources

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

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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