INHIBITION OF LIVER ACETYL-COENZYME-A CARBOXYLASE BY 2-TETRADECANYLGLUTARATE

Abstract

In a previous study (A. ENDO, et al., J. Antibiotics 38: 599-604, 1985), 2-alkyl glutarate and its derivatives isolated from cultures of Gongronella butleri were shown to inhibit animal acetyl-CoA carboxylase. In the present communication, the inhibition of liver acetyl-CoA carboxylase was investigated with several 2-alkyl glutarate and 2-alkyl succinate analogs. Their inhibitory potency increased with the chain length of the alkyl moiety, and 2-tetradecanylglutarate was most potent among the inhibitors tested. Kinetic analysis indicated that inhibition by 2-tetradecanylglutarate was non-competitive with respect to the substrates, ATP, HCO₃^-and acetyl-CoA, and competitive with respect to the allosteric regulator citrate, giving a Ki value of 40 μM. Sucrose density gradient centrifugation analysis showed that the citrate-induced polymerization of the enzyme was inhibited by 2-tetradecanylglutarate.