beta-Oxidation in human alcoholic and non-alcoholic hepatic steatosis.
1. The CoA and carnitine ester intermediates of mitochondrial beta-oxidation have not previously been quantified in liver disease, although there is some evidence that beta-oxidation is inhibited in alcoholic fatty liver. Mitochondria were isolated from needle liver biopsies from normal subjects, from patients with alcoholic fatty liver and patients with fatty liver of other aetiologies, incubated with 60 mumol/l [U-14C]hexadecanoate and the resultant CoA and carnitine esters were measured. 2. Although there was no significant difference in beta-oxidation flux between the patient groups, there was a significant rise in the proportion of 3-hydroxyacyl-CoA and 2-enoyl-CoA esters in patients with alcoholic fatty liver compared with normal subjects, and in patients with non-alcoholic fatty liver, suggesting an inhibition at the level of 3-hydroxyacyl-CoA dehydrogenase activity. 3. In alcoholic patients this difference could not be accounted for on the basis of the measured 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 the observed accumulation of CoA and carnitine esters, which may contribute to the accumulation of triacylglycerols in alcoholic steatosis. In fatty liver of other aetiologies, short- and long-chain 3-hydroxyacyl-CoA dehydrogenase activities were decreased.
Eaton
S
S
Department of Medicine, University of Newcastle upon Tyne, U.K.
Zaitoun
A M
AM
Record
C O
CO
Bartlett
K
K
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005234:Fatty Liver / Q000201:enzymology / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism*
D010168:Palmitates; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase