Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Sapporo 060-0812, Japan.
J Biochem. 2012 Nov;152(5):387-95. doi: 10.1093/jb/mvs105. Epub 2012 Sep 14.
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.
超长链脂肪酸（VLCFAs）是指碳链长度≥22 个碳原子的脂肪酸。哺乳动物具有多种 VLCFAs，其碳链长度和双键数量存在差异。每种 VLCFA 都具有特定的功能，例如在皮肤屏障形成、肝脏稳态、髓鞘维持、精子发生、视网膜功能和抗炎作用中发挥作用。这些功能不是由游离 VLCFAs 本身引起的，而是通过它们作为膜脂质（鞘脂和甘油磷脂）的成分或炎症缓解脂质介质的前体发挥作用的。VLCFAs 是通过内质网膜嵌入酶通过四步循环合成的。决定 VLCFAs 组织分布的最重要的酶是 FA 延长酶，它催化 FA 延长循环的第一步和限速步骤。哺乳动物有七种延长酶（ELOVL1-7），每种都表现出独特的底物特异性。几种遗传性疾病是由参与 VLCFA 合成或降解的基因突变引起的。在这篇综述中，我描述了哺乳动物和酵母中 FA 延长的分子机制以及负责的酶，以及人类与 VLCFA 相关的疾病。
