Very long-chain fatty acids: elongation, physiology and related disorders

J Biochem. 2012 Nov;152(5):387-95. doi: 10.1093/jb/mvs105. Epub 2012 Sep 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetyltransferases / metabolism
  • Animals
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / metabolism
  • Fatty Acid Elongases
  • Fatty Acids / biosynthesis
  • Fatty Acids / chemistry*
  • Fatty Acids / metabolism*
  • Humans
  • Ichthyosis / metabolism*
  • Macular Degeneration / congenital*
  • Macular Degeneration / metabolism

Substances

  • ELOVL1 protein, human
  • Fatty Acids
  • Acetyltransferases
  • Fatty Acid Elongases

Supplementary concepts

  • Stargardt disease 3