Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1.

ABSTRACT: Cytochrome P450 (P450, CYP) 17A1 plays a critical role in steroid metabolism, catalyzing both the 17α-hydroxylation of pregnenolone and progesterone and the subsequent 17α,20-lyase reactions to form dehydroepiandrosterone (DHEA) and androstenedione (Andro), respectively, critical for generating glucocorticoids and androgens. Human P450 17A1 reaction rates examined are enhanced by the accessory protein cytochrome b₅ (b₅), but the exact role of b₅ in P450 17A1-catalyzed reactions is unclear as are several details of these reactions. Here, we examined in detail the processivity of the 17α-hydroxylation and lyase steps. b₅ did not enhance reaction rates by decreasing the k_off rates of any of the steroids.

SUBMITTER: Gonzalez E 

PROVIDER: S-EPMC5555180 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature