title: Very long-chain fatty acids: elongation, physiology and related disorders.
abstract: Very long-chain fatty acids (VLCFAs) are fatty acids (FAs) with a chain-length of ≥22 carbons. Mammals have a variety of VLCFAs differing in chain-length and the number of double bonds. Each VLCFA exhibits certain functions, for example in skin barrier formation, liver homeostasis, myelin maintenance, spermatogenesis, retinal function and anti-inflammation. These functions are elicited not by free VLCFAs themselves, but through their influences as components of membrane lipids (sphingolipids and glycerophospholipids) or precursors of inflammation-resolving lipid mediators. VLCFAs are synthesized by endoplasmic reticulum membrane-embedded enzymes through a four-step cycle. The most important enzymes determining the tissue distribution of VLCFAs are FA elongases, which catalyze the first, rate-limiting step of the FA elongation cycle. Mammals have seven elongases (ELOVL1-7), each exhibiting a characteristic substrate specificity. Several inherited disorders are caused by mutations in genes involved in VLCFA synthesis or degradation. In this review, I describe the molecular mechanism of FA elongation and the responsible enzymes in mammals and yeast, as well as VLCFA-related disorders in human.
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Sapporo 060-0812, Japan. kihara@pharm.hokudai.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007057:Ichthyosis / Q000378:metabolism*; D008268:Macular Degeneration / Q000151:congenital* / Q000378:metabolism
chemical_list: C000630949:ELOVL1 protein, human; D005227:Fatty Acids; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases