alpha-Amanitin inhibits the oxidation of long chain fatty acids in mouse liver

It was found that the injection of the extract of Amanita virosa mushroom into mice resulted in the inhibition of long chain fatty acid oxidation by liver mitochondria. The inhibition principle was identified as alpha-amanitin. The inhibition was observed several hours after the injection of alpha-amanitin at the level of about 0.2 mg/kg, which corresponded to LD50. Activities of carnitine acyltransferases, acyl-CoA dehydrogenases, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase remained constant. Using fatty acids with various carbon chain lengths as substrates, the oxidation of long chain fatty acids was markedly inhibited with accompanying disappearance of the carnitine-dependent component. The decreases in the oxidation of medium and short chain fatty acids were less marked. It is suggested, therefore, that the site of the inhibition is the transport of long chain acylcarnitines. Peroxisomal beta-oxidation was not affected by the alpha-amanitin treatment.