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-N-Trimethyllysine Availability Regulates the Rate of Carnitine Biosynthesis in the Growing Rat^{1, 2,}

Charles J. Rebouche^*,,, Linda J. Lehman^* and Louise Olson

^* Department of Pediatrics The Program in Human Nutrition, University of Iowa College of Medicine, Iowa City, IA 52242

Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of -N-trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of [methyl-³H]-N-trimethyllysine, and approximately 30% of that was incorporated into tissues as [³H]carnitine. Rats given oral supplements of -N-trimethyllysine (0.5–20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receiving no dietary -N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary -N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral -N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of -N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of -N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat.

KEY WORDS: • -N-trimethyllysine • L-carnitine • metabolic regulation • rat

¹ Supported by U.S. Public Health Service Grant AM 35106 from the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases of the National Institutes of Health.

² Presented in part at the 69th annual meeting of the Federation of American Societies for Experimental Biology, Anaheim, CA, April 21–26, 1985. Rebouche, C. J. & Lehman, L. J. (1985) Availability of dietary -N-trimethyllysine for carnitine biosynthesis in the growing rat. Fed. Proc. 44, 763 (abs. 2057).

Manuscript received 26 July 1986. Revision accepted 24 January 1986.