Petrow V, Wang Y, Lack L, Sandberg A
Steroids. 1981 Aug;38(2):121-40. doi: 10.1016/0039-128x(81)90027-1.
Some derivatives of 6-methylene-4-pregnen-3-one were studied as inhibitors of delta 4-3-ketosteroid 5 alpha-reductase. Maximum inhibitory activity was shown by 17-acetoxy-6-methylene-4-pregnene-3,20-dione (AMPD). Irreversible inactivation was observed following preincubation of the enzyme with NADPH and AMPD. This inactivation was found to occur only in the presence of NADPH. As such enzyme inactivation was not due to the formation of a more inhibitory metabolic product, or to the formation of superoxide via a cytochrome P-450/NADPH pathway, it seemed likely that the observed inactivation was derived from an irreversible combination of the enzyme with AMPD. That this was probably the case was established by kinetic studies which revealed a pattern compatible with a kcat type of mechanism.
对6-亚甲基-4-孕甾烯-3-酮的一些衍生物作为δ4-3-酮甾体5α-还原酶抑制剂进行了研究。17-乙酰氧基-6-亚甲基-4-孕甾烯-3,20-二酮（AMPD）表现出最大抑制活性。用NADPH和AMPD对该酶进行预孵育后观察到不可逆失活。发现这种失活仅在NADPH存在下发生。由于这种酶失活不是由于形成了更具抑制性的代谢产物，也不是由于通过细胞色素P-450/NADPH途径形成超氧化物，因此观察到的失活似乎可能源于该酶与AMPD的不可逆结合。动力学研究证实了这可能是这种情况，该研究揭示了一种与kcat型机制相符的模式。
