Human cytochrome P450 27C1 catalyzes 3,4-desaturation of retinoids

In humans, a considerable fraction of the retinoid pool in skin is derived from vitamin A₂ (all-trans 3,4-dehydroretinal). Vitamin A₂ may be locally generated by keratinocytes, which can convert vitamin A₁ (all-trans retinol) into vitamin A₂ in cell culture. We report that human cytochrome P450 (hP450) 27C1, a previously 'orphan' enzyme, can catalyze this reaction. Purified recombinant hP450 27C1 bound and desaturated all-trans retinol, retinal, and retinoic acid, as well as 11-cis-retinal. Although the physiological role of 3,4-dehydroretinoids in humans is unclear, we have identified hP450 27C1 as an enzyme capable of efficiently mediating their formation.