S. Mccune, P. J. Durant, L. Flanders
Mar 1, 1982
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1
Influential Citations
41
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Journal
Archives of biochemistry and biophysics
Abstract
Abstract Benzoic acid, p-tert. -butylbenzoic acid, and a structurally related hypolipidemic agent SC-33459 were found to inhibit glucose synthesis by hepatocytes isolated from 48-h fasted rats as well as fatty acid synthesis by hepatocytes isolated from meal-fed rats. Glucose synthesis was less sensitive than fatty acid synthesis. Benzoic acid was the least effective inhibitor of both processes; SC-33459 and p-tert. -butylbenzoic acid were very potent inhibitors with similar efficacy. Glycine prevented the inhibition of fatty acid synthesis caused by benzoic acid, but had no effect on that caused by p-tert. -butylbenzoic acid. Octanoate opposed the inhibitory effects of both benzoic acid and p-tert. -butylbenzoic acid. Oxidation of [1- 14 C]oleate to ketone bodies and acid-soluble radioactive products was inhibited by both p-tert. -butylbenzoic acid and SC-33459. Preincubation of hepatocytes with SC-33459 was required for the latter effect, suggesting catabolism of this compound may be involved. SC-33459 is a p-tert. -butylphenyl derivative which should be readily converted to p-tert. -butylbenzoic acid by β oxidation. Both p-tert. -butylbenzoic acid and SC-33459 decreased citrate levels dramatically. All three compounds reduced CoA and acetyl-CoA levels and increased medium-chain acyl-CoA ester levels. p-tert. -Butylbenzoic acid and SC-33459 also increased long-chain acyl-CoA ester levels. The increase in medium-chain acyl-CoA levels presumably reflects benzoyl-CoA formation from benzoic acid and p-tert. -butylbenzoyl-CoA formation from p-tert. -butylbenzoic acid and SC-33459. Inhibition of glucose and fatty acid synthesis by these compounds may be due to effects on specific enzymes or to CoA sequestration.