Accepted name: ultra-long-chain fatty acid ω-hydroxylase
Reaction: an ultra-long-chain fatty acid + [reduced NADPH—hemoprotein reductase] + O2 = an ultra-long-chain ω-hydroxy fatty acid + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): CYP4F22 (gene name)
Systematic name: ultra-long-chain fatty acid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxylating)
Comments: The enzyme, which is expressed in the epidermis of mammals, catalyses the ω-hydroxylation of ultra-long-chain fatty acids (C28 to C36). The products are incorporated into acylceramides, epidermis-specific ceramide species that are very important for skin barrier formation.
1.  Ohno, Y., Nakamichi, S., Ohkuni, A., Kamiyama, N., Naoe, A., Tsujimura, H., Yokose, U., Sugiura, K., Ishikawa, J., Akiyama, M. and Kihara, A. Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation. Proc. Natl. Acad. Sci. USA 112 (2015) 7707–7712. [PMID: 26056268]
[EC created 2021]
Accepted name: ω-hydroxyceramide transacylase
Reaction: a linoleate-containing triacyl-sn-glycerol + an ultra-long-chain ω-hydroxyceramide = a diacyl-sn-glycerol + a linoleate-esterified acylceramide
Glossary: an ultra-long-chain fatty acid = ULCFA = a fatty acid with aliphatic chain of 28 or more carbons
an ultra-long-chain ω-hydroxyceramide = a ceramide that contains an ultra-long-chain ω-hydroxyfatty acid moiety (C28-C36)
acylceramide = ω-O-acylceramide = a ceramide that contains an ultra-long-chain ω-hydroxyfatty acid moiety (C28-C36) that is further extended by ω-esterification with linoleic acid.
Other name(s): PNPLA1 (gene name)
Systematic name: triacyl-sn-glycerol:ultra-long-chain ω-hydroxyceramide ω-O-linoleoyltransferase
Comments: The enzyme participates in the production of acylceramides in the stratum corneum, the outermost layer of the epidermis. Acylceramides are crucial components of the skin permeability barrier.
1.  Ohno, Y., Kamiyama, N., Nakamichi, S. and Kihara, A. PNPLA1 is a transacylase essential for the generation of the skin barrier lipid ω-O-acylceramide. Nat. Commun. 8:14610 (2017). [PMID: 28248318]
[EC created 2019]
Accepted name: ultra-long-chain ceramide synthase
Reaction: an ultra-long-chain fatty acyl-CoA + a sphingoid base = an ultra-long-chain ceramide + CoA
Glossary: a sphingoid base = an amino alcohol, composed predominantly of 18 carbon atoms, characterized by the presence of a hydroxyl group at C-1 (and often also at C-3), and an amine group at C-2.
an ultra-long-chain fatty acyl-CoA = an acyl-CoA with a chain length of 28 or longer.
Other name(s): mammalian ceramide synthase 3; sphingoid base N-ultra-long-chain fatty acyl-CoA transferase; CERS3 (gene name)
Systematic name: ultra-long-chain fatty acyl-CoA:sphingoid base N-acyltransferase
Comments: Mammals have six ceramide synthases that exhibit relatively strict specificity regarding the chain-length of their acyl-CoA substrates. Ceramide synthase 3 (CERS3) is the only enzyme that is active with ultra-long-chain acyl-CoA donors (C28 or longer). It is active in the epidermis, where its products are incorporated into acylceramides. CERS3 also accepts (2R)-2-hydroxy fatty acids and ω-hydroxy fatty acids, and can accept very-long-chain acyl-CoA substrates (see EC, very-long-chain ceramide synthase). It can use multiple sphingoid bases including sphinganine, sphingosine, phytosphingosine, and (6R)-6-hydroxysphingosine.
1.  Mizutani, Y., Kihara, A. and Igarashi, Y. LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity. Biochem. J. 398 (2006) 531–538. [PMID: 16753040]
2.  Mizutani, Y., Kihara, A., Chiba, H., Tojo, H. and Igarashi, Y. 2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length. J. Lipid Res. 49 (2008) 2356–2364. [PMID: 18541923]
3.  Jennemann, R., Rabionet, M., Gorgas, K., Epstein, S., Dalpke, A., Rothermel, U., Bayerle, A., van der Hoeven, F., Imgrund, S., Kirsch, J., Nickel, W., Willecke, K., Riezman, H., Grone, H.J. and Sandhoff, R. Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum. Mol. Genet. 21 (2012) 586–608. [PMID: 22038835]
4.  Mizutani, Y., Sun, H., Ohno, Y., Sassa, T., Wakashima, T., Obara, M., Yuyama, K., Kihara, A. and Igarashi, Y. Cooperative synthesis of ultra long-chain fatty acid and ceramide during keratinocyte differentiation. PLoS One 8:e67317 (2013). [PMID: 23826266]
[EC created 2019]