title: Human cytochrome P450 27C1 catalyzes 3,4-desaturation of retinoids.
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.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Kramlinger
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Nagy
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Rina
authors.initials: R
authors.lastname: Fujiwara
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Johnson
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Thanh T N
authors.initials: TT
authors.lastname: Phan
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Enright
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Toomey
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Corbo
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Frederick Peter
authors.initials: FP
authors.lastname: Guengerich
mesh_terms: D000072501:Cytochrome P450 Family 27 / Q000378:metabolism*; D006801:Humans; D012176:Retinoids / Q000378:metabolism*
chemical_list: D012176:Retinoids; C508522:CYP27C1 protein, human; D000072501:Cytochrome P450 Family 27
keywords: Cytochrome P450; desaturation; mass spectrometry; retinoids; spectroscopy