阿霉素作为肾上腺皮质线粒体中11β-羟化酶活性的抑制剂。

Adriamycin as an inhibitor of 11 beta-hydroxylase activity in adrenal cortex mitochondria.

作者信息

Cuéllar A, Escamilla E, Ramírez J, Chávez E

出版信息

Arch Biochem Biophys. 1984 Dec;235(2):538-43. doi: 10.1016/0003-9861(84)90227-3.

Abstract

Inhibition of 11 beta-hydroxylase activity was observed to be due to the interaction of adriamycin with adrenal cortex mitochondria. The inhibition of the enzyme was uncompetitive, with an apparent Ki of 100 microM, and was dependent upon the concentration of the drug and the time of incubation. Adriamycin increased the oxygen consumption of these mitochondria. EPR studies showed that adriamycin was reduced to a free radical semiquinone which served to shuttle electrons to oxygen, leading to an impairment in the reduction of cytochrome P450. It is suggested this may be the mechanism for the inhibitory effect of the drug on 11 beta-hydroxylase activity.

摘要

观察到阿霉素对11β-羟化酶活性的抑制作用是由于其与肾上腺皮质线粒体的相互作用。该酶的抑制作用是非竞争性的，表观抑制常数（Ki）为100微摩尔，且依赖于药物浓度和孵育时间。阿霉素增加了这些线粒体的耗氧量。电子顺磁共振研究表明，阿霉素被还原为自由基半醌，后者将电子传递给氧，导致细胞色素P450还原受损。提示这可能是该药物对11β-羟化酶活性产生抑制作用的机制。