Characterization and properties of carnitine acyltransferases.

lysine metabolism has been measured in rats fed a diet low in trimethyl-lysine and carnitine (Davis & Hoppel, 1983, 1986). Under these steady-state conditions, the total body trimethyl-lysine content is similar to the total body carnitine content. The tissue distribution of peptide-linked and free trimethyl-lysine shows that approximately 68% of the total trimethyl-lysine is present in skeletal muscle. In the steadystate, the urinary excretion of trimethyl-lysine and its metabolites will measure the amount of trimethyl-lysine produced and its conversion into carnitine. We have measured both urinary free trimethyl-lysine and N 2 -acetyl-trimethyl-lysine and determined that the plasma clearance of trimethyl-lysine is less than 5% of the glomerular filtration rate. Acetyltrimethyl-lysine accounts for about 70% of total trimethyllysine excretion. Other metabolites, such as 2-0x0-trimethylammonio-hexanoate, trimethylammonio-pentanoate and trimethylammonio-butanoate, account for less than 10% of trimethyl-lysine metabolism and are considered minor metabolites. In the steady state, carnitine excretion represents between 60 and 80% of the combined excretion of trimethyl-lysine and carnitine. Therefore, the conversion of endogenous trimethyl-lysine into carnitine appears to occur with a much higher efficiency than that observed with exogenous trimethyl-lysine. These data support the notion that trimethyl-lysine is converted into an intermediate, trimethylammonio-butanoate, in the tissue of origin and it is the intermediate that is the transported precursor for hepatic carnitine synthesis. Skeletal muscle contains the majority of trimethyl-lysine in the body and protein turnover rates in skeletal muscle are sufficiently high to suggest that it contributes substantially to the availability of trimethyl-lysine. The proposed sequence for formation of carnitine from extrahepatic sources of trimethyl-lysine would then be: