The role of fatty acid desaturase (FADS) genes in oleic acid metabolism: FADS1 Δ7 desaturates 11-20:1 to 7,11-20:2

摘要

IntroductionIn mammals,FADS2catalyzes “front-end” Δ4-, Δ6-, and Δ8-desaturation of fatty acyl chains, whereasFADS1has Δ5-desaturase activity. Eighteen and 20-carbon precursors to highly unsaturated n-3 and n-6 fatty acids are the usual substrates forFADS1andFADS2. Our main objective was to characterize the metabolic fate of oleic acid (OA) due to action ofFADSgene products. MethodsMCF-7 cells were stably transformed with eitherFADS1orFADS2or empty vector. A series of dose-response experiments were conducted with albumin-bound fatty acid substrates (18:1n-9 and 20:1n-9) provided in concentrations up to 100μM. Cells were harvested after 24h, after which FAME were prepared and analyzed by GC-FID and covalent adduct chemical ionization tandem mass spectrometry (CACI-MS/MS). ResultsWhen stably transformed cells were incubated with 18:1n-9,FADS1and control cells elongated 18:1n-9 → 20:1n-9 (11-20:1), whileFADS2cells Δ6 desaturated, elongated, and then Δ5 desaturated viaFADS1coded activity leading to Mead acid, 9-18:1 → 6,9-18:2 → 8,11-20:2 (20:2n-9) → 6,8,11-20:3 (20:3n-9). Surprisingly,FADS1cells Δ7 desaturated 11-20:1 → 7,11-20:2, the latter detected at low levels in control and FADS2 cells. Our results imply three pathways operate on 18:1n-9: 1) 18:1n-9 → 18:2n-9 → 20:2n-9 → 20:3n-9; 2) 18:1n-9 → 20:1n-9 → 20:2n-9 → 20:3n-9 and 3) 18:1n-9 → 20:1n-9 → 7,11-20:2. ConclusionAlternative pathways for oleic acid metabolism exist depending on FADS2 or FADS1 activities, we present the first evidence of Δ7 desaturation via theFADS1gene product