Effect of starvation on the disposition of free and peptide-linked trimethyllysine in the rat.

Free and peptide-linked trimethyllysine were measured in fed and 5-d starved rats. The trimethyllysine content of liver and kidney was significantly increased on d 5 of starvation to two to three times the levels found in fed animals. Skeletal muscle of fed rats contained over six times as much trimethyllysine (19.3 nmol/g) as that found in liver (3.2 nmol/g) or kidney (2.7 nmol/g). Plasma free trimethyllysine significantly increased from 1 nmol/ml in fed rats to 2.2 nmol/ml in 5-d starved rats. During this same period, daily total trimethyllysine excretions averaged approximately 400 nmol/d. Urinary free trimethyllysine was significantly depressed during starvation. Assuming that trimethyllysine in plasma does not exist in a protein-bound form, clearance calculations based on concentrations of plasma and urinary trimethyllysine indicated that this compound is readily reabsorbed by the kidney. As previous studies have indicated that trimethyllysine is not readily absorbed by other tissues, this indicates that the kidney may be the primary regulatory site for the disposition free of free trimethyllysine in plasma and urine. Estimates of the efficiency of entry of trimethyllysine into the carnitine biosynthetic pathway were calculated and ranged from 41% in 3-d starved rats to 80% in fed rats. We conclude that carnitine biosynthesis is limited by the availability of trimethyllysine, which, in the starved rat, is limited by the rate of protein turnover.