Elongation of very long chain fatty acids protein (ELOVL)

Very-long-chain fatty acid synthase (VLCFAS) refers to the enzyme complex, or specifically the rate-limiting condensing enzyme known as Elongation of very long chain fatty acids protein (ELOVL) in mammals, responsible for extending fatty acid chains beyond 16 carbons. [1][4] In humans, the ELOVL family consists of seven isoforms (ELOVL1-7) that catalyze the first and rate-limiting step of the four-step elongation cycle in the endoplasmic reticulum. [1][2] These enzymes are critical for the production of very-long-chain fatty acids (VLCFAs), which are essential for the synthesis of sphingolipids, skin barrier ceramides, and myelin. [2][4] ELOVL6, in particular, has gained significant attention as a therapeutic target for metabolic disorders, as its inhibition has been shown to protect against insulin resistance, hepatic steatosis, and obesity in animal models. [2] Additionally, VLCFAS is a well-established target for several classes of herbicides, such as chloroacetamides, which inhibit the enzyme to prevent the formation of the plant cuticle. [3] Therapeutic development for human applications faces challenges regarding the maintenance of essential VLCFA levels in the skin and brain to avoid adverse effects like ichthyosis or neurodegeneration. [2][4]

Other names

Very-long-chain fatty acid synthaseVLCFA synthaseVery-long-chain 3-oxoacyl-CoA synthase3-ketoacyl-CoA synthaseFatty acid elongase

Inhibition of the 3-ketoacyl-CoA synthase activity (the condensation step), which is the rate-limiting part of the fatty acid elongation cycle, thereby preventing the conversion of long-chain fatty acids to very-long-chain fatty acids.