Conversion of C21 to C19 requires two steps, 17a-hydroxylation and cleavage of the C17-20 bond, both of which are catalyzed by a single enzyme, the cytochrome P450 17a-hydroxylase/C17-20 lyase (P45017a). This enzyme catalyzes the bioconversion of pregnenolone and progesterone to the C19 steroids, dehydroepiandrosterone and androstenedione, respectively (56,57). In this two-step reaction, 17a-hydroxypreg-nenolone or 17a-hydroxyprogesterone exist as transient intermediates that are rapidly converted to dehydroepiandrosterone or androstenedione. The substrate preference and reaction velocities of P45017a differ, depending on the species and tissue source. In humans, P45017a has a higher affinity for 17a-hydroxypregnenolone, with dehydroepiandrosterone as the end product, and fails to show detectable C17-20 lyase activity with 17a-hydroxyprogesterone as substrate to generate androstenedione (58,59). In contrast, rat P45017a readily cleaves the A4-C21 17a-hydroxypregnenolone and A5-C21 17a-hydroxyprogesterone to dehydroepiandrosterone and androstenedione, respectively. Guinea pig P45017a also has a high affinity for A4-C21 steroids, (54), and both species contrast with the human, where the A5 pathway predominates
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