Increased plasma N,N,N-trimethyl-L-alanyl-L-proline betaine in ME patients

N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP) is a plasma biomarker of reduced kidney function (1).

Quote from ref 1:
"TMAP was the most consistently cleared metabolite by all hemodialysis modalities in our untargeted metabolomics analysis. Although the biological origin of TMAP has not been identified, we suggest that TMAP may be produced from degradation of myosin light chain (MYL) proteins. N,N,N-trimethylalanine is mainly found in myosin light chain (MYL) proteins and in each of the four MYL isoforms (MYL1, MYL2, MYL3, and MYL4), the c-terminus of N,N,N-trimethylalanine forms a peptide bond with proline (26). Therefore, MYL protein degradation may be responsible for the release of TMAP. Further study is necessary to determine the biological origin and potential physiological effects of TMAP."

Myosin light chains are components of macromcular myosin complexes. Fx. myosin II is the myosin type responsible for producing muscle contractions in muscle cells. Myosin II contains two heavy chains and four ligtht chains. ( Wikipedia. Myosin )

Plasma TMAP was increased in ME patients in Germain et al's metabolomic study (2020) (2).

As far as I know, ME patients have normal kidney function, so why is TMAP increased? Is the turnover of myosin light chains increased? And/or do the increased TMAP level reflect the breakdown of skeletal muscles?


Further reading about possible breakdown of skeletal muscles in ME patients :

Proline, P5C and 4-hydroxyglutamate in ME

http://followmeindenmark.blogspot.com/2020/02/proline-p5c-and-4-hydroxyglutamate-in-me.html

References:

1) Velenosi, T.J., Thomson, B.K.A., Tonial, N.C. et al. Untargeted metabolomics reveals N, N, N-trimethyl-L-alanyl-L-proline betaine (TMAP) as a novel biomarker of kidney function. Sci Rep 9, 6831 (2019). https://www.nature.com/articles/s41598-019-42992-3
https://doi.org/10.1038/s41598-019-42992-3 PMID: 31048706  PMCID: PMC6497643

2) Arnaud Germain , Dinesh K Barupal , Susan M Levine , Maureen R Hanson: Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids. Metabolites 2020, 10(1), 4; https://doi.org/10.3390/metabo10010034
https://www.mdpi.com/2218-1989/10/1/34