Fatty acid elongation occurs in three cellular compartments: the cytosol, mitochondria, and endoplasmic reticulum (microsomes). Microsomal fatty acid elongation is considered the predominant pathway for elongating fatty acids 12-carbons and longer. This pathway utilizes fatty acids derived from endogenous pathways, like de novo lipogenesis, as well as exogenous fatty acids derived from the diet. The overall pathway for microsomal fatty acid elongation involves four enzymes and fatty acyl CoA, malonyl CoA, and NADPH as substrates. In step 1, a 3-keto acyl-CoA synthase catalyzes the condensation of malonyl CoA with a fatty acyl-CoA precursor. These enzymes are called elongases and have been given the designation 'Elovl' for 'elongation of very long fatty acids'. They are conserved from yeast to mammals. The very-long-chain fatty acids they produce are essential for sphingolipid formation and function. (Adapted from
PMID:16564093 and
PMID:19763486.)
