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

  • FEBS Lett. 2016 May;590(9):1304-12. doi: 10.1002/1873-3468.12167.
Valerie M Kramlinger  1 ,  Leslie D Nagy  1 ,  Rina Fujiwara  1 ,  Kevin M Johnson  1 ,  Thanh T N Phan  1 ,  Yi Xiao  1 ,  Jennifer M Enright  2 ,  Matthew B Toomey  2 ,  Joseph C Corbo  2 ,  Frederick Peter Guengerich  1
Affiliations
  • 1. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • 2. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
PMID: 27059013 DOI: 10.1002/1873-3468.12167
Abstract

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.

Keywords
Cytochrome P450; desaturation; mass spectrometry; retinoids; spectroscopy.