FADS1
Description
The FADS1 (fatty acid desaturase 1) is a protein-coding gene located on chromosome 11.
Fatty acid desaturase 1 (FADS1) is an enzyme encoded by the FADS1 gene in humans. It belongs to the fatty acid desaturase (FADS) gene family and desaturates omega-3 and omega-6 polyunsaturated fatty acids at the delta-5 position, catalyzing the final step in the formation of eicosapentaenoic acid (EPA) and arachidonic acid. Desaturase enzymes like FADS1 regulate the unsaturation of fatty acids by introducing double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both characterized by conserved histidine motifs. The FADS1 gene is clustered with FADS1 and FADS2 at 11q12-q13.1, a cluster believed to have arisen from gene duplication due to its similar exon/intron organization. Single nucleotide polymorphisms (SNPs) of FADS1 and FADS2 may affect long-chain polyunsaturated fatty acids (LC-PUFA) metabolism and potentially contribute to the development of atopic diseases.
Isoform 1 of FADS1 acts as a front-end fatty acyl-coenzyme A (CoA) desaturase, introducing a cis double bond at carbon 5 between a preexisting double bond and the carboxyl end of the fatty acyl chain. It plays a crucial role in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors. Specifically, it desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to produce arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3), respectively. As a rate-limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived eicosanoid biosynthesis, it controls the metabolism of inflammatory lipids like prostaglandin E2, essential for efficient acute inflammatory response and maintenance of epithelium homeostasis. FADS1 contributes to membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major acyl chain esterified into phospholipids. Notably, it regulates phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory cytokine production in T-cells. Additionally, it desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of LA (18:2n-6).
FADS1 is also known as D5D, FADS6, FADSD5, LLCDL1, TU12.
