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3-羟基-3-甲基戊二酰二硫代辅酶A:米氏假单胞菌HMG-CoA还原酶的强效抑制剂。

3-Hydroxy-3-methylglutaryldithio-coenzyme A: a potent inhibitor of Pseudomonas mevalonii HMG-CoA reductase.

作者信息

Wrensford L V, Rodwell V W, Anderson V E

机构信息

Department of Chemistry, Brown University, Providence, Rhode Island 02912.

出版信息

Biochem Med Metab Biol. 1991 Apr;45(2):204-8. doi: 10.1016/0885-4505(91)90022-d.

Abstract

3-Hydroxy-3-methyl-1-thionoglutaryl-coenzyme A, a dithioester analog of 3-hydroxy-3-methylglutaryl-CoA, has been enzymatically synthesized using the HMG-CoA synthase catalyzed condensation of acetyl-CoA with 3-oxo-1-thionobutyryl-CoA. HMGdithio-CoA is a potent inhibitor of Pseudomonas mevalonii HMG-CoA reductase. Inhibition was mainly competitive with respect to HMG-CoA with a Kis of 0.086 +/- .01 microM and noncompetitive with respect to NADH with a Kis of 3.7 +/- 1.5 microM and a Kii of 0.65 +/- .05 microM in the presence of 110 microM (R.S)-HMG-CoA.

摘要

3-羟基-3-甲基-1-硫代戊二酰辅酶A是3-羟基-3-甲基戊二酰辅酶A的二硫酯类似物,它是利用HMG-CoA合酶催化乙酰辅酶A与3-氧代-1-硫代丁酰辅酶A缩合反应酶促合成的。HMG二硫代辅酶A是甲基营养型假单胞菌HMG-CoA还原酶的强效抑制剂。在110微摩尔(R.S)-HMG-CoA存在的情况下,抑制作用主要对HMG-CoA具有竞争性,Kis为0.086±0.01微摩尔,对NADH具有非竞争性,Kis为3.7±1.5微摩尔,Kii为0.65±0.05微摩尔。

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