The inhibition of long-chain fatty acyl-CoA synthetase by enoximone in rat heart mitochondria.

Abstract:

:The mechanism by which enoximone, a reported phosphodiesterase inhibitor, inhibits the oxidation of long-chain fatty acids was studied in isolated rat heart mitochondria using a series of 14C-labeled substrates. Enoximone decreased palmitate oxidation in a time- and concentration-dependent manner. Fifty percent inhibition of palmitate oxidation was achieved with 250 microM of enoximone. In contrast to its effect on palmitate, enoximone (250 microM) increased octanoate oxidation by 30%, whereas pyruvate oxidation was unaffected by enoximone. At that dose there was no effect on the oxidation of palmitoyl-CoA and palmitoyl carnitine. The degree of palmitate oxidation inhibited by enoximone was parallel to the inhibition of acyl-CoA synthetase in both rat heart mitochondria and microsomes. These results suggest that enoximone is a reversible inhibitor of long-chain fatty acyl-CoA synthetase. Moreover, the reaction, which is catalyzed by this enzyme, is a rate-limiting step in the pathway of fatty acid oxidation in rat heart mitochondria.

journal_name

J Cardiovasc Pharmacol

authors

Abdel-aleem S,Youssef J,Badr M,Morgan P,Frangakis C

doi

10.1097/00005344-199206000-00009

subject

Has Abstract

pub_date

1992-06-01 00:00:00

pages

899-904

issue

6

eissn

0160-2446

issn

1533-4023

journal_volume

19

pub_type

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