Inhibition of liver acetyl-coenzyme-A carboxylase by 2-tetradecanylglutarate.
In a previous study (A. ENDO, et al., J. Antibiotics 38: 599 approximately 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 regulatory citrate, giving a Ki value of 40 microM. Sucrose density gradient centrifugation analysis showed that the citrate-induced polymerization of the enzyme was inhibited by 2-tetradecanylglutarate.
Takeshima
H
H
Endo
A
A
Wada
K
K
Tanabe
T
T
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002499:Centrifugation, Density Gradient; D002645:Chickens; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D005977:Glutarates / Q000494:pharmacology*; D007700:Kinetics; D008025:Ligases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013386:Succinates / Q000494:pharmacology
D002951:Citrates; D005977:Glutarates; D013386:Succinates; D019343:Citric Acid; C048273:tetradecanylglutarate; D008025:Ligases; D000103:Acetyl-CoA Carboxylase