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Targeted Metabolomics Services

Trimethyllysine

TMLt
Updated 06/06/2023

What is measured?

Synonyms: N6,N6,N6-trimethyl-L-lysine, trimethyllysine, TML.
Method(s): LC-MS/MS (1).

What is trimethyllysine?

Trimethyllysine (TML), a methylated derivative of lysine, is produced through post-translational methylation of the amino acid in histone and is subsequently release through proteolysis. It is a precursor in the synthesis of carnitine, which together with betaine and choline are metabolized to the proatherogenic trimethylamine, TMAO. Circulating TML is associated with angiographic progression of coronary artery disease (2), and has recently been shown to be a strong predictor of incident cardiovascular disease, independent of TMAO (3).

Indication(s)

Assessment of endothelial function and cardiovascular risk.

Specimen, collection and processing

Matrix: EDTA plasma and serum.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: The blood sample must be centrifuged and the plasma/serum fraction put on ice, and frozen.

Transportation

Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: 0.3-2 µmol/L
Intraclass correlation coefficient (ICC): 0.37.

Literature

1. Midttun, O., Kvalheim, G., and Ueland, P.M. (2013). High-throughput, low-volume, multianalyte quantification of plasma metabolites related to one-carbon metabolism using HPLC-MS/MS. Anal Bioanal Chem 405, 2009-017.
2. Løland, K.H., Bleie, O., Borgeraas, H., Strand, E., Ueland, P.M., Svardal, A., Nordrehaug, J.E., and Nygård, O. (2013). The association between progression of atherosclerosis and the methylated amino acids asymmetric dimethylarginine and trimethyllysine. PLoS ONE 8, e64774.
3. Li, X.S., Wang, Z., Cajka, T., Buffa, J.A., Nemet, I., Hurd, A.G., Gu, X., Skye, S.M., Roberts, A.B., et al. (2018). Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight 3_e99096.

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Cardiometabolic
Inflammation
Microbiome
Nutrition
Categories

Amino acids, amino acid catabolites, acylcarnitines, TCA metabolites, ketone bodies, AGEs



Kynurenines, ratio-derived metabolites, proteins





SCFAs, indoles, choline metabolites, amino acid derived





B-vitamins, functional markers, and methyl donors, fat-soluble vitamins, essential amino acids, meat & fish intake, tobacco use & coffee intake
Biomarkers (n)
65
18
20
41
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Amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Kynurenine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Sarcosine, Serine, Threonine, Total cysteine, Tryptophan, Tyrosine, Valine

Amino acid catabolites: 2-Aminoadipic acid, 2-Hydroxybutyrate, 3-Hydroxysiobutyrate, α-Hydroxyglutaric acid, β-Alanine, β-Aminoisobutyrate, β-Hydroxy B-methylbutyric acid, Phenylacetylglutamine

Acylcarnities: BB, C0, C2, C3, C3-DC, C4, C4-OH, C4-DC, iC5, C5-DC, C5:1, C6, C8, C10, C12, C14, C14-OH, C16, C16-OH, C18, C18-OH, C18:1, C18:2

TCA metabolites: α-Ketoglutarate, Citrate, Fumarate, Isocitrate, Lactate, Malate, Pyruvate

Ketone bodies: Acetoacetate, 3-Hydroxybutyrate

AGEs: Carboxyethyllysine, Carboxymethyllysine

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Kynurenines: 3-hydroxykynurenine, 3-hydroxyanthranilic acid, Anthranilic acid, Kynurenine, Kynurenic acid, Nicotinic acid, Nicotinamide, N1-methylnicotinamide, Picolinic acid, Quinaldic acid, Quinolinic acid, Xanthurenic acid

Neopterin

Proteins: C-Reactive protein, Calprotectin, Serum Amyloid A

Ratio-derived: Kynurenine/tryptophan ratio, PAr index (PLP, PL, PA)

View

SCFAs: Acetate, Butyrate, Formate, Isobutyrate, Isovalerate, Propionate, Valerate, α-Methylbutyrate

Indoles: 3-Indoxyl sulfate, Imidazole propionate, Indole-3-acetamide, Indole-3-acetate, Indole-3-aldehyde, Indole-3-lactate, Indole-3-propionate

Choline metabolites: Choline, Betaine, DMG, TMAO

Amino acid derived: Phenylacetylglutamine

View

B-vitamins, functional markers, and methyl donors: 4-Pyridoxic acid, Betaine, Choline, Cobalamin, Flavin mononucleotide, Folate, Methylmalonic acid, N1-methylnicotinamide, Nicotinamide, Nicotinic acid, Pyridoxal, Pyridoxal 5-phosphate, Pyridoxine, Riboflavin, Thiamine, Thiamine monophosphate, Total homocysteine

Fat-soluble vitamins: 25-hydroxy vitamin D2, 25-hydroxy vitamin D3, α-Tocopherol (Vit. E), All-trans retinol (Vit. A), Phylloquinone (Vit. K1), y-Tocopherol (Vit. E)

Essential amino acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

Meat and fish intake: 1-Methylhistidine, 3-Methylhistidine, B-Alanine, Creatine, Creatinine, TMAO

Tobacco use and coffee intake: Cotinine, Trans-3-hydroxycotinine, Trigonelline

Volume (μl)
200
150
250
300
Analytical techniques
GC- and LC-MS/MS
LC- and MALDI-MS
GC- and LC-MS/MS
GC- and LC-MS/MS
Turnaround time (weeks)
1
1
1
1

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