Effect of acetaldehyde on fatty acid oxidation and ketogenesis by hepatic mitochondria

Arthur I. Cederbaum, Charles S. Lieber, Emanuel Rubin

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Abstract

Acetaldehyde inhibited the oxidation of fatty acids by rat liver mitochondria as assayed by oxygen consumption and CO2 production. ADP-stimulated oxygen uptake was more sensitive to inhibition by acetaldehyde than was uncoupler-stimulated oxygen uptake, suggesting an effect of acetaldehyde on the electron transport-phosphorylation system. This conclusion is supported by the decrease in the respiratory control ratio, associated with fatty acid oxidation. Acetaldehyde depressed ketone body production as well as the content of acetyl CoA during palmitoyl-1-carnitine oxidation. Acetaldehyde was considerably more inhibitory toward fatty acid oxidation than was acetate. Therefore, the inhibition by acetaldehyde is not mediated by acetate, the direct product of acetaldehyde oxidation by the mitochondria. Oxygen uptake was depressed by acetaldehyde to a slightly, but consistently, greater extent in the absence of fluorocitrate, than in its presence. This suggests inhibition of oxygen consumption from β-oxidation to acetyl CoA and that which arises from citric acid cycle activity. The inhibition of fatty acid oxidation is not due to any effect on the activation or translocation of fatty acids into the mitochondria. The depression of the end products of fatty acid oxidation (CO2, ketones, acetyl CoA) as well as the greater sensitivity of palmitate oxidation compared to acetate oxidation, suggests inhibition by acetaldehyde of β-oxidation, citric acid cycle activity, and the respiratory-phosphorylation chain. Neither the activities of palmitoyl CoA synthetase nor carnitine palmitoyltransferase appear to be rate limiting for fatty acid oxidation.

Original languageEnglish
Pages (from-to)29-41
Number of pages13
JournalArchives of Biochemistry and Biophysics
Volume169
Issue number1
DOIs
StatePublished - Jul 1975
Externally publishedYes

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