Elongase1

Elongase1, also known as fatty acid elongase 1 (ELOVL1), is an enzyme that plays a critical role in the biosynthesis of very-long-chain fatty acids (VLCFAs). This enzyme belongs to the elongase family, which catalyzes the elongation of fatty acyl-CoA substrates by adding two-carbon units derived from malonyl-CoA. ELOVL1 specifically functions in the elongation of saturated and monounsaturated fatty acids with chain lengths ranging from C12 to C20, contributing to the production of essential fatty acids like arachidonic acid (C20:4) and eicosapentaenoic acid (EPA, C20:5).

The gene encoding ELOVL1 is located on chromosome 6 in humans and is part of a cluster of elongase genes (ELOVL1–ELOVL7). Mutations in the ELOVL1 gene have been linked to neurological disorders, including spastic paraplegia type 4 (SPG4), a progressive motor neuron disease characterized by muscle stiffness and weakness. These mutations impair the enzyme’s ability to elongate fatty acids, leading to an accumulation of shorter-chain fatty acids and potential disruption of myelin sheath formation in nerve cells.

ELOVL1 is primarily expressed in tissues with high lipid demands, such as the brain, liver, and skin. Its activity is tightly regulated at both the transcriptional and post-translational levels, ensuring proper fatty acid homeostasis. The enzyme’s role extends beyond simple lipid synthesis, as VLCFAs are precursors for sphingolipids, which are essential components of cell membranes and signaling molecules. Dysregulation of ELOVL1 has also been implicated in metabolic disorders, including obesity and insulin resistance, highlighting its broader physiological significance.

Research into ELOVL1 continues to explore its potential as a therapeutic target for neurological and metabolic diseases. Understanding its function and regulation may lead to novel interventions for conditions where fatty acid metabolism is compromised.