Cytochrome P450 17A1, or steroid 17-alpha-monooxygenase, or 17α-hydroxylase/17,20 lyase/17,20 desmolase is an enzyme that in humans is encoded by the CYP17A1gene. It is found in the zona reticularis of the adrenal cortex and zona fasciculata as well as gonadal tissues. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are generally regarded as monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids, including the remarkable carbon-carbon bond scission catalyzed by this enzyme. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.
More specifically, CYP17A1 acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity), or acts upon 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side-chain off the steroid nucleus (the lyase activity).
The drug abiraterone which is used to treat castration-resistant prostate cancer blocks the biosynthesis of androgens by inhibiting the CYP17A1 enzyme. Abiraterone binds in the active site of the enzyme and coordinates the heme iron through its pyridine nitrogen, mimicking the subtrate.
17α-hydroxylase converts pregnenolone and progesterone to their 17-hydroxy forms, and converts 17-hydroxypregnenolone and 17-hydroxyprogesterone to DHEA and androstenedione, respectively. It corresponds to the downward arrows in this reaction scheme.
Steroidogenesis, showing, at left side, both reactions of 17-alpha hydroxylase, and both actions of 17, 20 lyase.
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