Takeshima H, Endo A, Wada K, Tanabe T
J Antibiot (Tokyo). 1986 Feb;39(2):275-80. doi: 10.7164/antibiotics.39.275.
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.
在之前的一项研究中（A. 远藤等人，《抗生素杂志》38: 599 - 604，1985年），从布氏共头霉培养物中分离出的2 - 烷基戊二酸及其衍生物被证明能抑制动物乙酰辅酶A羧化酶。在本报告中，用几种2 - 烷基戊二酸和2 - 烷基琥珀酸类似物研究了对肝脏乙酰辅酶A羧化酶的抑制作用。它们的抑制效力随烷基部分的链长增加而增强，在所测试的抑制剂中，2 - 十四烷基戊二酸最为有效。动力学分析表明，2 - 十四烷基戊二酸对底物ATP、HCO₃⁻和乙酰辅酶A的抑制作用是非竞争性的，而对变构调节物柠檬酸的抑制作用是竞争性的，其Ki值为40微摩尔。蔗糖密度梯度离心分析表明，2 - 十四烷基戊二酸可抑制柠檬酸诱导的该酶聚合。
