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Evidence That Cytochrome B5 Acts As A Redox Donor In Cyp17a1 Mediated Androgen Synthesis, Ruchia Duggal, Yilin Liu, Michael C. Gregory, Ilia G. Denisov, James R. Kincaid, Stephen G. Sligar

Chemistry Faculty Research and Publications

Cytochrome P450 17A1 (CYP17A1) is an important drug target for castration resistant prostate cancer. It is a bi-functional enzyme, catalyzing production of glucocorticoid precursors by hydroxylation of pregnene-nucleus, and androgen biosynthesis by a second C--C lyase step, at the expense of glucocorticoid production. Cytochrome b₅(cyt b₅) is known to be a key regulator of the androgen synthesis reaction in vivo, by a mechanism that is not well understood. Two hypotheses have been proposed for the mechanism by which cyt b₅ increases androgen biosynthesis. Cyt b₅ could act as an allosteric effector, binding to …