Elongation of very long chain fatty acids protein (ELOVL) (ELOVL)

Fatty acid elongases, primarily represented by the ELOVL (Elongation of Very Long chain fatty acids) protein family, are essential enzymes located in the endoplasmic reticulum that catalyze the rate-limiting condensation step of the fatty acid elongation cycle (UniProt, 2023; Jakobsson et al., 2006). This family consists of seven members (ELOVL1–7) in humans, each exhibiting unique substrate preferences for saturated, monounsaturated, or polyunsaturated fatty acids of varying chain lengths (Kihara, 2012). ELOVL6, which elongates C16 to C18 fatty acids, has emerged as a significant therapeutic target for metabolic disorders; its inhibition has been shown to improve insulin sensitivity and mitigate non-alcoholic steatohepatitis (NASH) in preclinical models (Matsuzaka & Shimano, 2014). ELOVL1 is targeted in the context of X-linked adrenoleukodystrophy to prevent the toxic accumulation of very-long-chain fatty acids (VLCFAs) (van de Beek et al., 2016). While small molecule inhibitors are being developed for metabolic and rare diseases, safety concerns include potential disruptions to the skin permeability barrier and ocular health, as certain ELOVL isoforms are critical for producing the specialized lipids required for these tissues (Sassa & Kihara, 2014).

Other names

Fatty acid elongase3-ketoacyl-CoA synthaseVLCFA elongaseLong-chain fatty acid elongaseKetoacyl-CoA synthase

Inhibition of the condensation of acyl-CoA with malonyl-CoA, the rate-limiting step in the fatty acid elongation cycle.