FADS2
Identifiers
AliasesFADS2, D6D, DES6, FADSD6, LLCDL2, SLL0262, TU13, fatty acid desaturase 2
External IDsOMIM: 606149 MGI: 1930079 HomoloGene: 3149 GeneCards: FADS2
Orthologs
SpeciesHumanMouse
Entrez

9415

56473

Ensembl

ENSG00000134824

ENSMUSG00000024665

UniProt

O95864

Q9Z0R9

RefSeq (mRNA)

NM_001281501
NM_001281502
NM_004265

NM_019699

RefSeq (protein)

NP_001268430
NP_001268431
NP_004256

NP_062673

Location (UCSC)Chr 11: 61.79 – 61.87 MbChr 19: 10.04 – 10.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
linoleoyl-CoA desaturase
Identifiers
EC no.1.14.19.3
CAS no.9014-34-0
Alt. namesD6D, FADS2, acyl-CoA 6-desaturase, delta-6-desaturase
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Linoleoyl-CoA desaturase (also Delta 6 desaturase, EC 1.14.19.3) is an enzyme that converts between types of fatty acids, which are essential nutrients in the human body. The enzyme mainly catalyzes the chemical reaction

linoleoyl-CoA + AH2 + O2 gamma-linolenoyl-CoA + A + 2 H2O

The three substrates of this enzyme are linoleoyl-CoA, an electron acceptor AH2, and O2, whereas its three products are gamma-linolenoyl-CoA, the reduction product A, and H2O.

This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with oxidation of a pair of donors resulting in the reduction of O to two molecules of water. The systematic name of this enzyme class is linoleoyl-CoA,hydrogen-donor:oxygen oxidoreductase. Other names in common use include acyl-CoA 6-desaturase, Delta6-desaturase (D6D or Δ-6-desaturase), Delta6-fatty acyl-CoA desaturase, Delta6-acyl CoA desaturase, fatty acid Delta6-desaturase, fatty acid 6-desaturase, linoleate desaturase, linoleic desaturase, linoleic acid desaturase, linoleoyl CoA desaturase, linoleoyl-coenzyme A desaturase, and long-chain fatty acid Delta6-desaturase. This enzyme participates in linoleic acid metabolism. It employs one cofactor, iron.

The enzyme is molecularly identical across all living things. It is present in animals, plants, fungi, and cyanobacteria.[5][6]

D6D is one of the three fatty acid desaturases present in humans along with Δ-5 and Δ-9, named so because it was thought to desaturate bond between carbons 6 and 7, counting from carboxyl group (with the carboxyl group carbon numbered one). The number 6 in the name of the enzyme has nothing to do with omega-6 fatty acids. In humans, D6D is encoded by the FADS2 gene.

Function

D6D is a desaturase enzyme, i.e. it introduces a double bond in a specific position of long-chain fatty acids. D6D is necessary to synthesize longer chain omega-3 and omega-6 fatty acids.[7] In humans, it is used principally for the conversions of cis-Linoleic acid to gamma-Linolenic acid (GLA), and palmitic acid to sapienic acid. It also converts alpha-Linolenic acid (ALA) to stearidonic acid and tetracosatetraenoic acid to tetracosapentaenoic acid, intermediate steps in the synthesis of ALA to EPA and of EPA to DHA, respectively.

Separately from its function in synthesizing EPA and DHA, D6D plays a contributory role in fatty acid re-esterification,[8] required for the return of unoxidized free fatty acids into white adipose tissue as triglycerides.

Agonists and inhibiting factors

D6D is upregulated by estrogen,[9] low levels of omega-3s, and moderate food restriction (up to 300%) .

D6D activity slows with age, suggested by reductions in GLA and subsequent metabolites.[10][11] Other inhibiting factors include alcohol, radiation, and diabetes .

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.[12]

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). It is implicated in abnormal sperm production due to deficiency in DHA[13] and atopic dermatitis due to deficiencies in GLA and PGE1.[14]

Toxoplasma gondii

Felines lack D6D activity in their guts and accumulate systemic linoleic acid.[15] This increase in linoleic acid in cats has an influence in causing the sexual cycle of T. gondii to be restricted to felines, with linoleic acid stimulating T. gondii sexual reproduction.[16]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134824 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024665 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Lee JM, Lee H, Kang S, Park WJ (January 2016). "Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances". Nutrients. 8 (1): 23. doi:10.3390/nu8010023. PMC 4728637. PMID 26742061.
  6. ↑ Nakamura MT, Nara TY (2004). "Structure, function, and dietary regulation of Δ6, Δ5, and Δ9 desaturases". Annual Review of Nutrition. 24: 345–376. doi:10.1146/annurev.nutr.24.121803.063211. PMID 15189125.
  7. ↑ Meena DK. "HUFA and PUFA: Structures, Occurrence, Biochemistry And Their Health Benefits". Aquafind Aquatic Fish Database.
  8. ↑ Wang, C.; Hucik, B.; Sarr, O.; Brown, L. H.; Wells, K. R. D.; Brunt, K. R.; Nakamura, M. T.; Harasim-Symbor, E.; Chabowski, A.; Mutch, D. M. (2023). "Delta-6 desaturase (Fads2) deficiency alters triacylglycerol/fatty acid cycling in murine white adipose tissue". Journal of Lipid Research. 64 (6): 100376. doi:10.1016/j.jlr.2023.100376. PMC 10323924. PMID 37085033.
  9. ↑ Giltay, E. J.; Gooren, L. J.; Toorians, A. W.; Katan, M. B.; Zock, P. L. (2004). "Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects". The American Journal of Clinical Nutrition. 80 (5): 1167–1174. doi:10.1093/ajcn/80.5.1167. ISSN 0002-9165. PMID 15531662.
  10. ↑ Horrobin, D. F. (1981). "Loss of delta-6-desaturase activity as a key factor in aging". Medical Hypotheses. 7 (9): 1211–1220. doi:10.1016/0306-9877(81)90064-5. ISSN 0306-9877. PMID 6270521.
  11. ↑ Biagi, P. L.; Bordoni, A.; Hrelia, S.; Celadon, M.; Horrobin, D. F. (1991). "Gamma-linolenic acid dietary supplementation can reverse the aging influence on rat liver microsome delta 6-desaturase activity". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1083 (2): 187–192. doi:10.1016/0005-2760(91)90041-F. ISSN 0005-2760. PMID 1674661.
  12. ↑ Gibson, R. A.; Neumann, M. A.; Lien, E. L.; Boyd, K. A.; Tu, W. C. (2012). "Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 88 (1): 139–146. doi:10.1016/j.plefa.2012.04.003. ISSN 0952-3278. PMID 22515943.
  13. ↑ Roqueta-Rivera M, Stroud CK, Haschek WM, Akare SJ, Segre M, Brush RS, Agbaga MP, Anderson RE, Hess RA, Nakamura MT (February 2010). "Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice". Journal of Lipid Research. 51 (2): 360–367. doi:10.1194/jlr.M001180. PMC 2803238. PMID 19690334.
  14. ↑ Chung, B. Y.; Park, S. Y.; Jung, M. J.; Kim, H. O.; Park, C. W. (2018). "Effect of Evening Primrose Oil on Korean Patients With Mild Atopic Dermatitis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Study". Annals of Dermatology. 30 (4): 409–416. doi:10.5021/ad.2018.30.4.409. PMC 6029968. PMID 30065580.
  15. ↑ Sinclair, A. J.; McLean, J. G.; Monger, E. A. (1979). "Metabolism of linoleic acid in the cat". Lipids. 14 (11): 932–936. doi:10.1007/BF02533508. ISSN 1558-9307. PMID 513981. S2CID 4023638.
  16. ↑ Knoll, Laura J.; Dubey, J. P.; Wilson, Sarah K.; Genova, Bruno Martorelli Di (2019-07-01). "Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction". bioRxiv: 688580. doi:10.1101/688580.
  • Okayasu T, Nagao M, Ishibashi T, Imai Y (1981). "Purification and partial characterization of linoleoyl-CoA desaturase from rat liver microsomes". Arch. Biochem. Biophys. 206 (1): 21–28. doi:10.1016/0003-9861(81)90061-8. PMID 7212717.
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