Fig. 1.

(A) CYP17A1 mediates two major types of reactions, initial 17α-hydroxylation (blue) of pregnenolone or progesterone, followed by a 17,20-lyase reaction (magenta) on 17α-hydroxypregnenolone. While only the latter 17,20-lyase reaction is necessary for androgen biosynthesis, downstream products of the hydroxylase reaction include important glucocorticoids such as cortisol. Inhibition of CYP17A1 by abiraterone (green) inhibits both CYP17A1-mediated reaction types, resulting in the desired net decrease in androgens but an undesirable decrease in glucocorticoids. The decrease in glucocorticoids results in an overproduction of mineralocorticoids as a result of adrenocorticotropin hormone feedback. (B) Abiraterone (green sticks) inhibits both CYP17A1 reactions by directly coordinating the CYP17A1 heme (black sticks with red iron sphere at center) required for catalysis.