title: Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Ji Yao
authors.initials: JY
authors.lastname: Zhang
authors.forename: Kumar S D
authors.initials: KS
authors.lastname: Kothapalli
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D023421:Models, Animal; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; C000630967:ELOVL2 protein, human; C000630954:ELOVL5 protein, human; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005819:Genetic Markers; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
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