Reaction: a phytoceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (2'R)-2'-hydroxyphytoceramide + 2 ferricytochrome b5 + H2O
Glossary: a phytoceramide = a (4R)-4-hydroxysphinganine ceramide = an N-acyl-4-hydroxysphinganine
Other name(s): FA2H (gene name); SCS7 (gene name)
Systematic name: (4R)-4-hydroxysphinganine ceramide,ferrocytochrome-b5:oxygen oxidoreductase (fatty acyl 2-hydroxylating)
Comments: The enzyme, characterized from yeast and mammals, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to (4R)-4-hydroxysphinganine during de novo ceramide synthesis. The enzymes from yeast and from mammals contain an N-terminal cytochrome b5 domain that acts as the direct electron donor to the desaturase active site. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.7, dihydroceramide fatty acyl 2-hydroxylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Mitchell, A.G. and Martin, C.E. Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion protein, and its Arabidopsis thaliana homolog that lacks the cytochrome b5 domain both function in the α-hydroxylation of sphingolipid-associated very long chain fatty acids. J. Biol. Chem. 272 (1997) 28281-28288. [PMID: 9353282]
2. Dunn, T.M., Haak, D., Monaghan, E. and Beeler, T.J. Synthesis of monohydroxylated inositolphosphorylceramide (IPC-C) in Saccharomyces cerevisiae requires Scs7p, a protein with both a cytochrome b5-like domain and a hydroxylase/desaturase domain. Yeast 14 (1998) 311-321. [PMID: 9559540]
3. Alderson, N.L., Rembiesa, B.M., Walla, M.D., Bielawska, A., Bielawski, J. and Hama, H. The human FA2H gene encodes a fatty acid 2-hydroxylase. J. Biol. Chem. 279 (2004) 48562-48568. [PMID: 15337768]
4. Eckhardt, M., Yaghootfam, A., Fewou, S.N., Zoller, I. and Gieselmann, V. A mammalian fatty acid hydroxylase responsible for the formation of α-hydroxylated galactosylceramide in myelin. Biochem. J. 388 (2005) 245-254. [PMID: 15658937]
5. Guo, L., Zhang, X., Zhou, D., Okunade, A.L. and Su, X. Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers. J. Lipid Res. 53 (2012) 1327-1335. [PMID: 22517924]