Inhibition of acetyl-carnitine oxidation in rat brown-adipose-tissue mitochondria by erucoyl-carnitine is due to sequestration of CoA.

The cause underlying the inhibitory effect of erucoyl-carnitine on acetyl-carnitine oxidation in rat brown-adipose-tissue mitochondria was investigated. The inhibition was shown to be of a noncompetitive nature, with an I50 of about 10 microM erucoyl-carnitine. Erucoyl-carnitine did not inhibit the respiratory chain or the citric acid cycle to a significant degree. Incubation of mitochondria with erucoyl-carnitine led to about 2/3 of all CoA being sequestered in the form of acid-insoluble esters (probably erucoyl-CoA). This sequestration had an apparent Km of about 10 microM. Erucoyl-carnitine also inhibited pyruvate oxidation with an I50 of about 10 microM. When added at this concentration, it also inhibited the oxidation of a wide variety of acyl-carnitines by about 50%, despite very different oxidation rates of these different acyl-carnitines. It was concluded that the inhibitory effect of erucoyl-carnitine on all CoA-dependent substrates could be adequately explained by the suggestion that erucoyl sequesters a significant fraction of mitochondrial matrix CoA as slowly metabolizable erucoyl-CoA esters. Possible physiological effects of this sequestration for brown adipose tissue thermogenesis are discussed.