Inherited defects of mitochondrial fatty acid oxidation.

soma1 oxidase ( H 2 0 , production). Nevertheless, mitochondrial oxidation of sebacyl-carnitine could be recorded. This activity was 10-20% of that measured in the same mitochondrial preparation with palmitoyl-CoA ( + L-carnitine) or decanoyl-carnitine. Further, there was no indication of interference by sebacyl-CoA with carnitine palmitoyltransferase. In conclusion, intravenously infused dodecanedioic acid is readily catabolized in control rats in which less than 30% of the infused dose is recovered in urine as shorter dicarboxylates. Further experiments with radiolabelled dicarboxylates are necessary to determine the fate of the remaining 70%; the possibility exists that they are completely oxidized in mitochondria. Indeed, we showed by experiments in vitro that mitochondria are able to oxidize dicarboxyl-carnitine esters, although the mechanism of formation of these esters was not elucidated. Dicarboxyl-carnitine esters do not appear to be formed by mitochondrial carnitine palmitoyltransferase. Riboflavin deficiency, which induces a profound impairment of the activities of mitochondrial, but not of peroxisomal, flavoproteins and thus induces by itself a dicarboxylic aciduria, considerably increases the proportion of dicarboxylates recovered in urine from the infused dodecanedioic acid. The administration of clofibrate, a drug which, among other effects, stimulates both mitochondrial and peroxisomal poxidation in rats, strongly decreases the excretion of dicarboxylates in urine.