Edwards P A, Lan S F, Tanaka R D, Fogelman A M
J Biol Chem. 1983 Jun 25;258(12):7272-5.
3-Hydroxy-3-methylglutaryl(HMG)-coenzyme A reductase purified from rat liver in the absence of protease inhibitors is composed of two distinct polypeptides of Mr = 51,000 and 52,500. Antibody raised to enzyme purified from rats fed a diet supplemented with cholestyramine and mevinolin inactivated HMG-CoA reductase. The antibody specifically precipitated a polypeptide of Mr = 94,000 from rat liver cells that had been previously incubated with [35S]methionine. The immunoprecipitation of the 35S-labeled polypeptide of Mr = 94,000 was prevented by addition of unlabeled pure HMG-CoA reductase (Mr = 51,000 and 52,500). Incubation of rat liver cells with mevalonolactone resulted in a decreased activity of HMG-CoA reductase and in a 40% decrease in the rate of incorporation of [35S]methionine into the immunoprecipitable reductase polypeptide of Mr = 94,000. In pulse-chase experiments, mevalonolactone enhanced the rate of degradation of the Mr = 94,000 polypeptide 3-fold. We propose that endogenous microsomal HMG-CoA reductase has a subunit of Mr = 94,000 and that the synthesis and degradation of this polypeptide are regulated by either mevalonolactone or, more likely, a product of mevalonolactone metabolism.
在没有蛋白酶抑制剂的情况下从大鼠肝脏中纯化得到的3-羟基-3-甲基戊二酰（HMG）-辅酶A还原酶由两种不同的多肽组成，其相对分子质量分别为51,000和52,500。用从喂食考来烯胺和洛伐他汀补充饮食的大鼠中纯化得到的酶制备的抗体可使HMG-CoA还原酶失活。该抗体从先前用[35S]甲硫氨酸孵育过的大鼠肝细胞中特异性沉淀出一种相对分子质量为94,000的多肽。加入未标记的纯HMG-CoA还原酶（相对分子质量为51,000和52,500）可阻止相对分子质量为94,000的35S标记多肽的免疫沉淀。用甲羟戊酸内酯孵育大鼠肝细胞会导致HMG-CoA还原酶活性降低，并且[35S]甲硫氨酸掺入相对分子质量为94,000的可免疫沉淀还原酶多肽的速率降低40%。在脉冲追踪实验中，甲羟戊酸内酯使相对分子质量为94,000的多肽降解速率提高了3倍。我们推测内源性微粒体HMG-CoA还原酶有一个相对分子质量为94,000的亚基，并且该多肽的合成和降解受甲羟戊酸内酯或更可能是甲羟戊酸内酯代谢产物的调节。
