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Effect of Starvation on the Disposition of Free and Peptide-Linked Trimethyllysine in the Rat1, 2,

Alan T. Davis3 and Charles L. Hoppel

Veterans Administration Medical Center and Departments of Pharmacology and Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106

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 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.


KEY WORDS: • trimethyllysine • carnitine biosynthesis

1 Supported by National Institutes of Health Grants AM-15804, AM-21009 and AM-07319, and the Medical Research Service of the Veterans Administration.

2 Presented in part at the Federation of American Societies for Experimental Biology Annual Meeting, 1982, New Orleans, L.A.

3 Present address: Nutrition Research Laboratory, Butterworth Hospital, 100 Michigan NE, Grand Rapids, MI 49503.

Manuscript received 13 August 1985. Revision accepted 7 January 1986.







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