Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and sterol synthesis by cholesterol sulfate in cultured fibroblasts.
Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and sterol synthesis by cholesterol sulfate in cultured fibroblasts.
复制标题
硫酸胆固醇在培养的成纤维细胞中抑制 3-羟基-3-甲基戊二酰辅酶 A 还原酶活性和甾醇合成。
DOI：
10.1016/0167-4889(85)90198-3
复制
发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Elias,PM
中科院分区：
文献类型：
--
作者：
Williams,ML;Hughes-Fulford,M;Elias,PM
虽然广泛分布于哺乳动物的组织中，但硫酸胆固醇的生物学功能仍然很大程度上未知。在这些研究中，我们已经证明硫酸胆固醇可以抑制培养的人成纤维细胞中重新合成固醇。在这些培养的细胞中进一步显示，胆固醇硫酸盐是酶3-羟基-3-甲基戊二酰辅酶A还原酶（甲羟戊酸：NADP+氧化还原酶（CoA-酰化），EC 1.1.1.34）的有效抑制剂，所述酶是胆固醇生物合成中的限速酶和外源性胆固醇抑制内源性胆固醇合成的位点。由于硫酸胆固醇抑制了来自隐性X连锁鱼鳞病患者的类固醇硫酸酯酶缺陷成纤维细胞中的类固醇生成，因此推断这些研究中的抑制剂是硫酸胆固醇本身，而不是细胞内胆固醇释放。胆固醇硫酸盐可能是哺乳动物胆固醇生物合成的内源性调节剂。
Although widely distributed throughout mammalian tissues, the biological function of cholesterol sulfate remains largely unknown. In these studies we have demonstrated that cholesterol sulfate suppresses de novo sterol synthesis in cultured human fibroblasts. It was further shown in these cultured cells that cholesterol sulfate is a potent inhibitor of the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (mevalonate: NADP+oxidoreductase (CoA-acylating), EC 1.1.1.34), the rate-limiting enzyme in cholesterol biosynthesis and the site at which exogenous cholesterol suppresses endogenous cholesterol synthesis. Because cholesterol sulfate inhibited sterologenesis in steroid-sulfatase deficient fibroblasts derived from patients with recessive X-linked ichthyosis, it was inferred that cholesterol sulfate per se and not cholesterol liberated by intracellular desulfation was the inhibitor in these studies. Cholesterol sulfate may be an endogenous regulator of mammalian cholesterol biosynthesis.