Abstract
CYP2W1 is a recently discovered human cytochrome P450 enzyme with a distinctive tumor-specific expression pattern. We show here that CYP2W1 exhibits tight binding affinities for retinoids, which have low nanomolar binding constants, and much poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts all-trans retinoic acid (atRA) to 4-hydroxy atRA and all-trans retinol to 4-OH all-trans retinol, and it also oxidizes retinal. The enzyme much less efficiently oxidizes 17β-estradiol to 2-hydroxy-(17β)-estradiol and farnesol to a monohydroxylated product; arachidonic acid is, at best, a negligible substrate. These findings indicate that CYP2W1 probably plays an important role in localized retinoid metabolism that may be intimately linked to its involvement in tumor development.
Footnotes
- Received January 25, 2015.
- Accepted February 29, 2016.
This research was supported by National Institutes of Health National Institute of General Medical Sciences [Grant GM25515], the National Institute of Environmental Health Sciences [Grant R01 EX002710 and P42 Superfund Program], and the West Coast Central Comprehensive Metabolomic Research Core [U24 DK097154].
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- Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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