BETA-OXIDATION IN HUMAN ALCOHOLIC AND NONALCOHOLIC HEPATIC STEATOSIS

1. The CoA and carnitine ester intermediates of mitochondrial beta-oxi dation have not previously been quantified in liver disease, although there is some evidence that beta-oxidation is inhibited in alcoholic f atty liver, Mitochondria were isolated from needle liver biopsies from normal subjects, from patients with alcoholic fatty liver and patient s with fatty liver of other aetiologies, incubated with 60 mu mol/l [U -C-14]hexadecanoate and the resultant CoA and carnitine esters were me asured, 2. Although there was no significant difference in beta-oxidat ion flux between the patient groups, there was a significant rise in t he proportion of 3-hydroxyacyl-CoA and 2-enoyl-CoA esters in patients with alcoholic fatty liver compared with normal subjects, and in patie nts with non-alcoholic fatty liver, suggesting an inhibition at the le vel of 3-hydroxyacyl-CoA dehydrogenase activity,3. In alcoholic patien ts this difference could not be accounted for on the basis of the meas ured activity of short and long-chain 3-hydroxyacyl-CoA dehydrogenases , and it is suggested that either an inhibition of complex I activity or diminished amounts of ubiquinone are likely to be responsible for t he observed accumulation of CoA and carnitine esters, which may contri bute to the accumulation of triacylglycerols in alcoholic steatosis, I n fatty liver of other aetiologies, short- and long-chain 3-hydroxyacy l-CoA dehydrogenase activities were decreased.