AI Article Synopsis
- Cytochromes P450 17A1 (CYP17A1) and 21A2 (CYP21A2) are crucial enzymes in producing various steroid hormones, like mineralocorticoids and glucocorticoids.
- Researchers synthesized fluorinated versions of pregnenolone and progesterone to investigate how these modifications affect enzyme activity.
- The introduction of fluorine at specific sites inhibited certain reactions of CYP17A1 and CYP21A2 while allowing substrate entry, suggesting fluorine could help steer steroid metabolism towards targeted hormones.
Article 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 substitutions examined herein prevented compound entry into the active sites of either CYP17A1 or CYP21A2 as demonstrated by spectral binding assays. Taken together, the results suggest that fluorine might be used to redirect the metabolic pathways of pregnenolone and progesterone to specific types of steroids.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042386 | PMC |
| http://dx.doi.org/10.1039/d1ob01178b | DOI Listing |
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