Role of Lysine and s-NTrimethyllysine in Carnitine Biosynthesis

We have previously reported that weanling rats fed a 20% wheat gluten diet, limiting in lysine and containing no detectable carnitine, have significantly lower levels of carnitine in skeletal and heart muscle than rats receiving adequate dietary lysine. Rats on 20% wheat gluten diets were administered appropriate levels of DL-[6-i*C]lysine, L-[mefhyZ3H]methionine, t-N-[mefhyZ-3H]trimethyl-L-lysine, or [carboxy-l*C]y-butyrobetaine. Carnitine was subsequently isolated by ion exchange chromatography from a number of tissues and examined for radioactivity. In most trials about 0.1% of administered DL-[6-i*C]lysine or L-[mefhyZ-3H]methionine was incorporated into tissue carnitine. Dietary lysine significantly decreased the utilization of DL-[6-r*C]lysine for carnitine synthesis. Radioactivity following administration of nL-[2-‘4C]lysine was not detected in biosynthesized tissue carnitine. e-N-[mefhyZ-3H]Trimethyl-L-lysine and [carboxyW]y-butyrobetaine were converted in high yield to carnitine, e.g. 23 and 45% of administered dose per 100 g of skeletal muscle. Radioactive carnitine was also detected in the urine in these latter instances. It was shown that t-Ntrimethyllysine is converted to y-butyrobetaine in the rat. These data support the thesis that lysine is a precursor of carnitine in the rat, which together with similar labeling studies in Neurospora suggest the following transformations: lysine --+ e-N-trimethyllysine --+ y-butyrobetaine + carnitine.