Trimethyllysine

TMLt

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: 0.4 -1.3 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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