CYP4F22

CYP4F22, like other CYP4F proteins, is a Cytochrome P450 omega hydroxylase, i.e. an enzyme that metabolizes fatty acids to their omega hydroxyl derivatives (see Omega oxidation). This hydroxylation may: a) produce a biologically important signaling molecule such as occurs in the metabolism of 20-carbon straight chain polyunsaturated fatty acid, arachidonic acid, to 20-Hydroxyeicosatetraenoic acid, b) inactivate a biologically important product such as the metabolism of the arachidonic acid metabolite, 5-oxo-eicosatetraenoic acid, to its ~100-fold less potent product, 5-oxo-20-hydroxy-eicosatetraenoic acid, or c) be the first step in the further metabolism of xenobiotics or natural compounds[7] CYP4F22 serves the latter function. It is a type 1 Integral membrane protein located in the endoplasmic reticulum of cells in the stratum granulosum of mammalian, including human, skin where it functions to attach an omega hydroxyl residue to fatty acids that are exceptionally long, 28 or more carbons, i.e. the very long chain fatty acids (VLCFA).[8][9] These VLCFA targets need not be free fatty acids but also can be acylated in an amide bond to sphingosine to form an acylceramide.

CYP4F22 omega hydroxylates the VLCFA in esterified omega-oxyacyl-sphingosine complex to form an esterified omega-hydroxyacyl-sphingosine complex. This step is critical for delivering the wax-like, extremely hydrophobic VLCFA to the stratum corneum near the skin surface. It is these skin surface VLCFA which create and maintain the skin's ability to function as a water barrier.[10][11][12]

CYP4F22, like many of the CYP4F series of CYPs, may prove to serve other functions but its role in hydroxylating VLCFA in the skin's water barrier function, as defined in genetic studies (see below), has dominated research on it.

A small number of newborns with Congenital ichthyosiform erythroderma have been found to have autosomal recessive lose of function mutations in CYP4F22.[13][14] Of the varies subtypes of congenital ichthyosiform erythroderma, these mutations have been associated almost exclusively with the Lamellar ichthyosis subtype.[14]

• Strausberg, RL; Feingold, EA; Grouse, LH; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Kimura, K; Wakamatsu, A; Suzuki, Y; et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Fischer, J; Faure, A; Bouadjar, B; et al. (2000). "Two New Loci for Autosomal Recessive Ichthyosis on Chromosomes 3p21 and 19p12-q12 and Evidence for Further Genetic Heterogeneity". Am. J. Hum. Genet. 66 (3): 904–13. doi:10.1086/302814. PMC 1288171. PMID 10712205.
• Elias, PM; Williams, ML; Holleran, WM; et al. (2008). "Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism". J. Lipid Res. 49 (4): 697–714. doi:10.1194/jlr.R800002-JLR200. PMC 2844331. PMID 18245815.
• Nelson, DR; Zeldin, DC; Hoffman, SM; et al. (2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics. 14 (1): 1–18. doi:10.1097/00008571-200401000-00001. PMID 15128046.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.