2016
DOI: 10.1002/1873-3468.12167
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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 physio… Show more

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Cited by 30 publications
(29 citation statements)
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“…CYP27C1 lacks a prototypical N-terminus and initiates coding in the middle of canonical helix C, at a position analogous to the alternative start site used by CYP24A1-SV1 (Ren et al, 2005). CYP27C1 is expressed in liver, kidney, pancreas, and several other tissues, and remained an orphan for over a decade (Wu et al, 2006), until recently, when it was shown to mediate the conversion of vitamin A1 (all-trans retinol) into vitamin A2 (all-trans 3,4-dehydroretinal) in cell culture (Kramlinger et al, 2016). It is intriguing that CYP27C1 may represent a codified version of the more soluble P450 isotype recapitulated by CYP24-SV1, and that this transition may mediate a general switch between vitamin A and vitamin D substrate specificity.…”
Section: Meta-analysis Of Alternative Gene Splicing In the Cytochromementioning
confidence: 99%
“…CYP27C1 lacks a prototypical N-terminus and initiates coding in the middle of canonical helix C, at a position analogous to the alternative start site used by CYP24A1-SV1 (Ren et al, 2005). CYP27C1 is expressed in liver, kidney, pancreas, and several other tissues, and remained an orphan for over a decade (Wu et al, 2006), until recently, when it was shown to mediate the conversion of vitamin A1 (all-trans retinol) into vitamin A2 (all-trans 3,4-dehydroretinal) in cell culture (Kramlinger et al, 2016). It is intriguing that CYP27C1 may represent a codified version of the more soluble P450 isotype recapitulated by CYP24-SV1, and that this transition may mediate a general switch between vitamin A and vitamin D substrate specificity.…”
Section: Meta-analysis Of Alternative Gene Splicing In the Cytochromementioning
confidence: 99%
“…Oxidation of all-trans-retinol to 3-and 4-OH products-We previously reported that human P450 27C1 oxidized retinol to a product that co-eluted with 4-OH retinol (Fig. 2), in addition to the desaturation product 3,4-dehydroretinol (25). However, we did not have any independent evidence for its identity.…”
Section: Identification Of Reaction Productsmentioning
confidence: 59%
“…Substrate binding-We had previously shown that human P450 27C1 forms a tight complex with all-trans-retinol, shifting the heme Soret peak from the low-to high-spin iron form ("Type I" difference spectrum), with an estimated K d of ϳ5.6 nM (25). The rate of binding was measured using two different approaches.…”
Section: Individual Reaction Steps and Catalytic Mechanismmentioning
confidence: 99%
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