Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis
| Autor: | J. Thomas Brenna, Ji Yao Zhang, Kumar S.D. Kothapalli |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Fatty Acid Desaturases
Genetic Markers 0301 basic medicine Fatty Acid Elongases Medicine (miscellaneous) Endogeny Polymorphism Single Nucleotide Article 03 medical and health sciences Delta-5 Fatty Acid Desaturase 0302 clinical medicine Acetyltransferases Fatty Acids Omega-3 Gene cluster Animals Humans Polyunsaturated fatty acid biosynthesis Alleles chemistry.chemical_classification Elongase Nutrition and Dietetics biology Limiting 030104 developmental biology Fatty acid desaturase Biochemistry chemistry Multigene Family Models Animal Fatty Acids Unsaturated biology.protein Long chain 030217 neurology & neurosurgery Genome-Wide Association Study Polyunsaturated fatty acid |
| Zdroj: | Current Opinion in Clinical Nutrition and Metabolic Care. 19:103-110 |
| ISSN: | 1363-1950 |
| DOI: | 10.1097/mco.0000000000000254 |
| Popis: | Endogenous synthesis of the long-chain polyunsaturated fatty acids (LCPUFAs) is mediated by the fatty acid desaturase (FADS) gene cluster (11q12-13.1) and elongation of very long-chain fatty acids 2 (ELOVL2) (6p24.2) and ELOVL5 (6p12.1). Although older biochemical work identified the product of one gene, FADS2, rate limiting for LCPUFA synthesis, recent studies suggest that polymorphisms in any of these genes can limit accumulation of product LCPUFA.Genome-wide association study (GWAS) of Greenland Inuit shows strong adaptation signals within FADS gene cluster, attributed to high omega-3 fatty acid intake, while GWAS found ELOVL2 associated with sleep duration, age and DNA methylation. ELOVL5 coding mutations cause spinocerebellar ataxia 38, and epigenetic marks were associated with depression and suicide risk. Two sterol response element binding sites were found on ELOVL5, a SREBP-1c target gene. Minor allele carriers of a 3 single nucleotide polymorphism (SNP) haplotype in ELOVL2 have decreased 22 : 6n-3 levels. Unequivocal molecular evidence shows mammalian FADS2 catalyzes direct Δ4-desaturation to yield 22 : 6n-3 and 22 : 5n-6. An SNP near FADS1 influences the levels of 5-lipoxygenase products and epigenetic alteration.Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway. |
| Databáze: | OpenAIRE |
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