The role of carnitine in the conjugation of acidic xenobiotics.

Conjugation with carnitine is a major metabolic pathway for cyclopropanecarboxylic acid (CPCA). The CPCA-carnitine is cleaved enzymatically (carnitine acetyltransferase) more slowly in vitro than are acetyl- and propionylcarnitines, but also slightly more extensively. When given orally to a rat, CPCA-carnitine is excreted readily in urine as free CPCA and its glycine conjugate. Effects of dietary exposure of rats to CPCA were determined by feeding cycloprate (a CPCA precursor) at 5000 ppm and then assaying tissue levels of carnitine. Both free and total carnitine in the hearts of female rats were depressed by 39% after 3 weeks at this exaggerated dose. We suggest a possible link between sequestration of carnitine and the observed pathology which includes lipid deposition in the hearts of female rats fed cycloprate at high doses. When a rat was given an oral dose of [14C]benzoic acid, benzoylcarnitine was a minor urinary metabolite (0.04% of applied dose). This result suggests that many other xenobiotic acids may conjugate with carnitine (albeit at low levels) and this role in xenobiotic metabolism may be more general than presently appreciated.