COMPETITIVE INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE BY ML-236A AND ML-236B FUNGAL METABOLITES, HAVING HYPOCHOLESTEROLEMIC ACTIVITY
COMPETITIVE INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE BY ML-236A AND ML-236B FUNGAL METABOLITES, HAVING HYPOCHOLESTEROLEMIC ACTIVITY
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DOI：
10.1016/0014-5793(76)80996-9
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发表时间：
1976-01-01
期刊：
影响因子：
3.5
通讯作者：
TANZAWA, K
中科院分区：
文献类型：
--
作者：
ENDO, A;KURODA, M;TANZAWA, K
真菌代谢物ML 236 A和ML 236 B（Bg. l），已在本实验室中从桔青霉菌培养物中分离出作为胆固醇合成的有效抑制剂[l]。这些代谢物（小鼠LD 5e> 2 g，每OS）导致大鼠[1]以及母鸡和狗（Kitano、Tsujita和Endo，准备中）血清胆固醇水平显著降低。本文报道的实验表明，MG-236 A和ML-236 B特异性抑制3-羟基-3-甲基戊二酰（HMG）-CoA还原酶（EC 1. I. 1.34），胆固醇合成途径中的限速酶，而不影响参与该途径的其余酶，并且该抑制相对于底物HMG-CoA是竞争性的。
Fungal metabolites, ML236A and ML236B (Bg. l), have been isolated from cultures of Penicillium citinum as potent inhibitors of cholesterol synthesis in vitro in this laboratory [l]. These metabolites (LD5e for mice> 2 g, per OS) cause a marked decrease in serum cholesterol levels in rats [l], and in hens and dogs (Kitano, Tsujita and Endo, in preparation). The experiments reported in this paper demonstrate that MG236A and ML-236B inhibit specifically 3-hydroxy-3-methylglutaryl(HMG)-CoA reductase (EC 1. I. 1.34), the rate-limiting enzyme in cholesterol synthetic pathway, without affecting the rest of the enzymes involved in this pathway, and that the inhibition is competitive with respect to the substrate HMG-CoA.