A novel inhibitor of steroid biosynthesis [11]
A novel inhibitor of steroid biosynthesis [11]
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一种新型类固醇生物合成抑制剂[11]
DOI：
10.1021/ja00483a050
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发表时间：
1978
影响因子：
15
通讯作者：
Ta
中科院分区：
文献类型：
--
作者：
J. Nelson;M. Czarny;T. A. Spencer;J. S. Limanek;K. McCrae;Ta
在类固醇生物合成后期C-4氧化去甲基化的研究中，我们发现，1958年首次制备的4,4,10 /3-三甲基- z /YZ/M-decal-3/3-ol2 （1， TMD）具有重要的生化特性。本文所述的证据表明，TMD在大鼠肝酶制剂和培养的哺乳动物细胞中都是胆固醇生物合成的特异性抑制剂，并表明抑制作用发生在氧化角鲨烯的环化上。最初的实验是为了确定TMD是否可以作为4,4 -二甲基类固醇的双环类似物，并被标准Sio大鼠肝脏均质物（Sio- rlh）去甲基化。然而，当用tritrium6标记的c//-TMD5与Sio-RLH孵育时，未检测到去甲基化产物。主要产物为4,4,10 j8 -三甲基-二烷基萘-3/ 3,7 /3-二醇(2)。这个代谢物，iden-
During studies1 of the oxidative demethylation at C-4 in the latter stages of steroid biosynthesis we have discovered that4, 4, 10/3-trimethyl-Z/YZ/M-decal-3/3-ol2 (1, TMD), first prepared in 1958, 3 has important biochemical properties. The evidence described herein demonstrates that TMD is a specific inhibitor of cholesterol biosynthesis in both rat liver enzyme preparations and cultured mammalian cells, and indicatesthat inhibition occurs at the cyclization of squalene oxide. Initial experiments were run to determine whether TMD would act as a bicyclic analogue of 4, 4-dimethyl steroids and be demethylated by a standard Sio rat liver homogenate4 (Sio-RLH). However, when c//-TMD5 labeled with tritium6 was incubated with Sio-RLH, no demethylated product was detected. Instead, 4, 4, 10J8-trimethyl-iz-ato-decalin-3/3, 7/3-diol (2) was isolated as the major product. This metabolite, iden-