Catalytic activities of tumor-specific human cytochrome P450 CYP2W1 toward endogenous substrates

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 lownanomolar binding constants, andmuch poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts alltrans 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 17b-estradiol to 2-hydroxy-(17b)-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.