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Utilization of Dietary Precursors for Carnitine Synthesis in Human Adults¹

Charles J. Rebouche^*, E. Peter Bosch^**, Catherine A. Chenard, Kay J. Schabold and Steven E. Nelson^*

^* Department of Pediatrics ^** Department of Neurology General Clinical Research Center, University of Iowa College of Medicine, Iowa City, IA 52242

Endogenous synthetic pathways are presumed to be sufficient to provide adequate amounts of carnitine to meet the needs of the body. However, circulating carnitine levels of strict vegetarian adults and children, and particularly of infants fed carnitine-free formulas, are significantly lower than normal. Therefore, we investigated loci at which rates of carnitine synthesis may be restricted in human adults. Excess amounts of the carnitine precursors lysine plus methionine, -N-trimethyllysine or -butyrobetaine were fed as supplements to a low carnitine diet for 10 d. Rate of carnitine synthesis was estimated by changes in carnitine excretion and changes in serum and muscle carnitine levels. Dietary -butyrobetaine dramatically increased camitine production, -N-trimethyllysine had a somewhat smaller effect, and lysine plus methionine had even less effect on carnitine synthesis. We conclude that carnitine synthesis is not limited by the activity of -butyrobetaine hydroxylase. Carnitine synthesis from exogenous -N-trimethyllysine is limited either by enzymatic processes that lead to the final intermediate, -butyrobetaine, or by the ability of this substrate to enter tissues capable of carrying out these transformations.

KEY WORDS: • L-carnitine biosynthesis • -N-trimethyl-L-lysine • -butyrobetaine • L-lysine • L-methionine • metabolic regulation • adult humans

¹ Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-35106) and The General Clinical Research Centers Branch, Division of Research Resources (RR-00059), U.S. Public Health Service.

Manuscript received 20 January 1989. Revision accepted 24 July 1989.

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