Inhibition of Lipid Synthesis by Alpha-Phenyl-N-Butyrate and Related Compounds

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Abstract
Cottet et al. report lowering of serum cholesterol levels in rats and in man by feeding alpha-phenylbutyrate (La Presse Medicale, 62(44): 939-941. 1954.). This compound at 1 x 10-3 M is found to strongly inhibit incorporation of acetate-l-Cl4 into aceto-acetate, cholesterol and fatty acids by rat liver slices without inhibiting O2 uptake. Rats fed alpha-phenylbutyrate 200 mg/kg/ day for 4 weeks showed no change in liver concentration of cholesterol or coenzyme A. Three aromatic acids structurally related to alpha-phenylbutyrate also acted as effective inhibitors of lipid synthesis (alpha, alpha -diphenylbutyrate; beta, beta1-diphenyl-alpha-ethylpropionate; alpha, alpha1-diphenylvalerate). alpha, alpha1-Diphenylvalerate were effective down to 1 x 10-5 M. The possible relationship of drug potentiation by the latter compound to its effect on acetate metabolism is discussed.