FADS2
Enzyme found in humans
From Wikipedia, the free encyclopedia
Fatty acid desaturase 2 (FADS2) is an enzyme that in humans is encoded by the FADS2 gene.[5][6]
| FADS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | FADS2, D6D, DES6, FADSD6, LLCDL2, SLL0262, TU13, fatty acid desaturase 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 606149; MGI: 1930079; HomoloGene: 3149; GeneCards: FADS2; OMA:FADS2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Function
Desaturation
The protein encoded by the FADS2 gene is a member of the fatty acid desaturase (FADS) gene family. It has three catalytic activities acting on fatty-acid-CoA:[7]
- As a Delta 6 desaturase, it desaturates omega-3 and omega-6 polyunsaturated fatty acids at the delta-6 position, catalyzing the first and rate-limiting step in the formation of tetracosapentaenoic acid and tetracosahexaenoic acid.
- As a Delta 8 desaturase, desaturation at the delta-8 position.
- As a Delta 4 desaturase, desaturation at the delta-4 position.[8]
Desaturase enzymes (such as those encoded by FADS2) cause desaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization.[5]
Re-esterification
Separately from its function in synthesizing EPA and DHA, D6D plays a contributory role in fatty acid re-esterification,[9] required for the return of unoxidized free fatty acids into white adipose tissue as triglycerides.
Agonists and inhibiting factors
D6D is upregulated by estrogen,[10] low levels of omega-3s, and moderate food restriction (up to 300%) [citation needed].
D6D activity slows with age, suggested by reductions in GLA and subsequent metabolites.[11][12] Other inhibiting factors include alcohol, radiation, and diabetes [citation needed].
The conversion rate of ALA into DHA is vulnerable to suppression by dietary fatty acids. ALA intake greater than 1% and total polyunsaturated intake above 3% were found to drastically limit synthesis of EPA and DHA.[13]
Clinical significance
D6D deficiency can result in deficiencies in DHA, and in GLA and its metabolites dihomo-gamma-linolenic acid (DGLA) and prostaglandin E1 (PGE1).
Sperm quality
It is implicated in abnormal sperm production due to deficiency in DHA[14] and atopic dermatitis due to deficiencies in GLA and PGE1.[15]
Intelligence in breast-fed children
An early study claimed to find an association between FADS2 and the IQ of breastfed children, but this result failed to be replicated in later studies. In particular, the original study reported that breastfed children with the rs174575 "C" version of the gene had an IQ (intelligence quotient) 7 points higher than those with the less common rs174575 "G" version (less than this when adjusted for maternal IQ).[16][17]
An attempt to replicate this study in 5934 8-year-old children failed: No relationship of the common rs174575 C allele to negative effects of formula feeding was apparent, and contra to the original report, the rare rs174575 GG homozygote children performed worse when formula fed than other children on formula milk.[18] A study of over 700 families recently found no evidence for either main or moderating effects of the original SNP (rs174575), nor of two additional FADS2 polymorphisms (rs1535 and rs174583), nor any effect of maternal FADS2 status on offspring IQ.[19]
