Effects of fluorine substitution on substrate conversion by cytochromes P450 17A1 and 21A2.

ABSTRACT: Cytochromes P450 17A1 (CYP7A1) and 21A2 (CYP21A2) catalyze key reactions in the production of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens. With the ultimate goal of designing probes that are selectively metabolized to each of these steroid types, fluorinated derivatives of the endogenous substrates, pregnenolone and progesterone, were prepared to study the effects on CYP17A1 and CYP21A2 activity. In the functional assays, the hydroxylase reactions catalysed by each of these enzymes were blocked when fluorine was introduced at the site of metabolism (positions 17 and 21 of the steroid core, respectively). CYP17A1, furthermore, performed the 17,20-lyase reaction on substrates with a fluorine installed at the 21-position. Importantly, none of the substitutio

SUBMITTER: Vogt CD 

PROVIDER: S-EPMC10042386 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature