Description
Fatty acid desaturase 2 (FADS2), also known as Δ
6-desaturase, is a 444-amino acid transmembrane protein encoded by
FADS2. This product is the N-terminal cytoplasmic domain of FADS2, corresponding to residues 2-131 of the full-length sequence. It catalyzes the rate-limiting step in the conversion of the ω-6 and ω-3 precursors linoleic acid (Item Nos.
90150 |
21909) and α-linolenic acid to their respective long-chain polyunsaturated fatty acids (LC-PUFAs), inserting a
cis double bond at position 6 of the fatty acid chain to convert linoleic acid to γ-linolenic acid and α-linolenic acid to stearidonic acid , respectively. Following secondary desaturation by FADS1 and chain elongation, FADS2 catalyzes desaturation of 24-carbon LC-PUFA intermediates. FADS2 also catalyzes the desaturation of palmitic acid to sapienic acid in human sebaceous glands and in various cancer cell lines that express FADS2. Hepatic FADS2 protein levels and mRNA expression are increased in mice with high-fat diet-induced obesity and non-alcoholic steatohepatitis (NASH). FADS2 knockout (
fads2-/-) mice are infertile, resistant to obesity, and have altered subcellular membrane diacylglycerol composition which leads to dysregulated post-translational processing of SREBP1c, a key transcription factor in the regulation of lipid metabolism.
References
[1] LAN GE . Identification of the Δ-6 Desaturase of Human Sebaceous Glands: Expression and Enzyme Activity[J]. Journal of Investigative Dermatology, 2003, 120 5: Pages 707-714. DOI:
10.1046/j.1523-1747.2003.12123.x[2] KIM VRIENS. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity[J]. Nature, 2019, 566 7744: 403-406. DOI:
10.1038/s41586-019-0904-1[3] WILHELM STOFFEL. Obesity resistance and deregulation of lipogenesis in Δ6-fatty acid desaturase (FADS2) deficiency.[J]. EMBO Reports, 2014: 110-120. DOI:
10.1002/embr.201338041
