The Role of Fatty Acid Desaturase (FADS) Genes in Oleic Acid Metabolism: FADS1 Δ7 desaturates 11-20:1 to 7,11-20:2
| Autor: | Kumar S.D. Kothapalli, Hui Gyu Park, Peter Lawrence, J. Thomas Brenna, Kyle Vogt-Lowell, Matthew G. Engel |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Fatty Acid Desaturases Stereochemistry FADS1 FADS2 Clinical Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid Delta-5 Fatty Acid Desaturase Mead acid Fatty Acids Omega-6 Humans FADS1 Gene chemistry.chemical_classification biology Fatty Acids Fatty acid Cell Biology Metabolism Oleic acid 030104 developmental biology Fatty acid desaturase chemistry biology.protein MCF-7 Cells Oleic Acid |
| Popis: | Introduction In mammals, FADS2 catalyzes “front-end” Δ4-, Δ6-, and Δ8-desaturation of fatty acyl chains, whereas FADS1 has Δ5-desaturase activity. Eighteen and 20-carbon precursors to highly unsaturated n-3 and n-6 fatty acids are the usual substrates for FADS1 and FADS2. Our main objective was to characterize the metabolic fate of oleic acid (OA) due to action of FADS gene products. Methods MCF-7 cells were stably transformed with either FADS1 or FADS2 or 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 100 µM. Cells were harvested after 24 h, after which FAME were prepared and analyzed by GC-FID and covalent adduct chemical ionization tandem mass spectrometry (CACI-MS/MS). Results When stably transformed cells were incubated with 18:1n-9, FADS1 and control cells elongated 18:1n-9 → 20:1n-9 (11-20:1), while FADS2 cells Δ6 desaturated, elongated, and then Δ5 desaturated via FADS1 coded 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, FADS1 cells 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. Conclusion Alternative pathways for oleic acid metabolism exist depending on FADS2 or FADS1 activities, we present the first evidence of Δ7 desaturation via the FADS1 gene product |
| Databáze: | OpenAIRE |
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