{{Short description|Enzyme found in humans}} {{cs1 config|name-list-style=vanc}} {{Infobox_gene}} '''Fatty acid desaturase 2''' ('''FADS2''') is an enzyme that in humans is encoded by the ''FADS2'' gene.<ref name="entrez"/><ref name="pmid10860662">{{cite journal |vauthors=Marquardt A, Stöhr H, White K, Weber BH | title = cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family | journal = Genomics | volume = 66 | issue = 2 | pages = 175–83 |date=June 2000 | pmid = 10860662 | doi = 10.1006/geno.2000.6196 }}</ref>

== 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:<ref>{{cite journal|last1=Brenna|first1=J Thomas|title=An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Δ8-desaturates 20:2n-6 and 20:3n-3|journal=Journal of Lipid Research|date=June 2009|volume=50|issue=6|pages=1195–202|doi=10.1194/jlr.M800630-JLR200 |doi-access=free |pmid=19202133|pmc=2681401}}</ref> * 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.<ref name=pmid26065859>{{cite journal |last1=Park |first1=HG |last2=Park |first2=WJ |last3=Kothapalli |first3=KS |last4=Brenna |first4=JT |title=The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells. |journal=FASEB Journal |date=September 2015 |volume=29 |issue=9 |pages=3911–9 |doi=10.1096/fj.15-271783 |doi-access=free |pmid=26065859|pmc=4550368 }}</ref>

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.<ref name="entrez">{{cite web | title = Entrez Gene: FADS1 fatty acid desaturase 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3992}}</ref>

=== Re-esterification === Separately from its function in synthesizing EPA and DHA, D6D plays a contributory role in fatty acid re-esterification,<ref>{{Cite journal|last1=Wang|first1=C.|last2=Hucik|first2=B.|last3=Sarr|first3=O.|last4=Brown|first4=L. H.|last5=Wells|first5=K. R. D.|last6=Brunt|first6=K. R.|last7=Nakamura|first7=M. T.|last8=Harasim-Symbor|first8=E.|last9=Chabowski|first9=A.|last10=Mutch|first10=D. M.|date=2023|title=Delta-6 desaturase (''Fads2'') deficiency alters triacylglycerol/fatty acid cycling in murine white adipose tissue|journal=Journal of Lipid Research|language=en|volume=64|issue=6|article-number=100376|doi=10.1016/j.jlr.2023.100376|pmid=37085033|doi-access=free|pmc=10323924}}</ref> required for the return of unoxidized free fatty acids into white adipose tissue as triglycerides.

==Agonists and inhibiting factors==

{{Expand section|citations|small=no|date=December 2023}}

D6D is upregulated by estrogen,<ref>{{Cite journal|last1=Giltay|first1=E. J.|last2=Gooren|first2=L. J.|last3=Toorians|first3=A. W.|last4=Katan|first4=M. B.|last5=Zock|first5=P. L.|date=2004|title=Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects|journal=The American Journal of Clinical Nutrition|language=en|volume=80|issue=5|pages=1167–1174|doi=10.1093/ajcn/80.5.1167|pmid=15531662|issn=0002-9165|doi-access=free}}</ref> low levels of omega-3s, and moderate food restriction (up to 300%) {{Citation needed|date=December 2023}}.

D6D activity slows with age, suggested by reductions in GLA and subsequent metabolites.<ref>{{Cite journal|last1=Horrobin|first1=D. F.|date=1981|title=Loss of delta-6-desaturase activity as a key factor in aging|journal=Medical Hypotheses|language=en|volume=7|issue=9|pages=1211–1220|doi=10.1016/0306-9877(81)90064-5|pmid=6270521|issn=0306-9877}}</ref><ref>{{Cite journal|last1=Biagi|first1=P. L.|last2=Bordoni|first2=A.|last3=Hrelia|first3=S.|last4=Celadon|first4=M.|last5=Horrobin|first5=D. F.|date=1991|title=Gamma-linolenic acid dietary supplementation can reverse the aging influence on rat liver microsome delta 6-desaturase activity|journal=Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism|language=en|volume=1083|issue=2|pages=187–192|doi=10.1016/0005-2760(91)90041-F|pmid=1674661|issn=0005-2760}}</ref> Other inhibiting factors include alcohol, radiation, and diabetes {{Citation needed|date=December 2023}}.

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.<ref>{{Cite journal|last1=Gibson|first1=R. A.|last2=Neumann|first2=M. A.|last3=Lien|first3=E. L.|last4=Boyd|first4=K. A.|last5=Tu|first5=W. C.|date=2012|title=Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids|journal=Prostaglandins, Leukotrienes, and Essential Fatty Acids|language=en|volume=88|issue=1|pages=139–146|doi=10.1016/j.plefa.2012.04.003|pmid=22515943|issn=0952-3278}}</ref>

==Clinical significance== D6D deficiency can result in deficiencies in DHA, and in GLA and its metabolites dihomo-gamma-linolenic acid (DGLA) and prostaglandin E<sub>1</sub> (PGE<sub>1</sub>).

=== Sperm quality === It is implicated in abnormal sperm production due to deficiency in DHA<ref name="ncbi2010">{{cite journal | vauthors = Roqueta-Rivera M, Stroud CK, Haschek WM, Akare SJ, Segre M, Brush RS, Agbaga MP, Anderson RE, Hess RA, Nakamura MT | title = Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice | journal = Journal of Lipid Research | volume = 51 | issue = 2 | pages = 360–367 | date = February 2010 | pmid = 19690334 | pmc = 2803238 | doi = 10.1194/jlr.M001180 |doi-access=free }}</ref> and atopic dermatitis due to deficiencies in GLA and PGE<sub>1</sub>.<ref>{{Cite journal|last1=Chung|first1=B. Y.|last2=Park|first2=S. Y.|last3=Jung|first3=M. J.|last4=Kim|first4=H. O.|last5=Park|first5=C. W.|date=2018|title=Effect of Evening Primrose Oil on Korean Patients With Mild Atopic Dermatitis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Study|journal=Annals of Dermatology|language=en|volume=30|issue=4|pages=409–416|doi=10.5021/ad.2018.30.4.409|pmid=30065580|doi-access=free|pmc=6029968}}</ref>

===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).<ref>[http://www.physorg.com/news113505546.html Gene governs IQ boost from breastfeeding].</ref><ref name="pmid17984066">{{cite journal |vauthors=Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ, Poulton R, Schalkwyk LC, Taylor A, Werts H, Moffitt TE | title = Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 47 | pages = 18860–5 |date=November 2007 | pmid = 17984066 | pmc = 2141867 | doi = 10.1073/pnas.0704292104 | bibcode = 2007PNAS..10418860C | doi-access = free }}</ref>

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.<ref name="pmid20644632">{{cite journal |vauthors=Steer CD, Davey Smith G, Emmett PM, Hibbeln JR, Golding J | title = FADS2 polymorphisms modify the effect of breastfeeding on child IQ | journal = PLOS ONE | volume = 5 | issue = 7 | article-number = e11570 | year = 2010 | pmid = 20644632 | pmc = 2903485 | doi = 10.1371/journal.pone.0011570 | bibcode = 2010PLoSO...511570S | doi-access = free }}</ref> 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.<ref name="pmid21156270">{{cite journal |vauthors=Martin NW, Benyamin B, Hansell NK, Montgomery GW, Martin NG, Wright MJ, Bates TC | title = Cognitive function in adolescence: testing for interactions between breast-feeding and FADS2 polymorphisms | journal = J Am Acad Child Adolesc Psychiatry | volume = 50 | issue = 1 | pages = 55–62.e4 |date=January 2011 | pmid = 21156270 | doi = 10.1016/j.jaac.2010.10.010 }}</ref>

==References== {{reflist}}

==Further reading== {{refbegin | 2}} *{{cite journal |vauthors=Zabaneh D, Balding DJ |title=A genome-wide association study of the metabolic syndrome in Indian Asian men. |journal=PLOS ONE |volume=5 |issue= 8 |article-number= e11961 |year= 2010 |pmid= 20694148 |doi= 10.1371/journal.pone.0011961 |pmc=2915922|bibcode=2010PLoSO...511961Z |doi-access=free }} *{{cite journal |vauthors=Lattka E, Illig T, Koletzko B, Heinrich J |title=Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism. |journal=Curr. Opin. Lipidol. |volume=21 |issue= 1 |pages= 64–9 |year= 2010 |pmid= 19809313 |doi= 10.1097/MOL.0b013e3283327ca8 |s2cid=7723575 }} *{{cite journal |vauthors=Xie L, Innis SM |title=Association of fatty acid desaturase gene polymorphisms with blood lipid essential fatty acids and perinatal depression among Canadian women: a pilot study. |journal=J. Nutr. Nutr. |volume=2 |issue= 4–5 |pages= 243–50 |year= 2009 |pmid= 20395685 |doi= 10.1159/000255636 |s2cid=9818163 |doi-access=free }} *{{cite journal |vauthors=Kwak JH, Paik JK, Kim OY |title=FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. |journal=Atherosclerosis |volume=214 |issue= 1 |pages= 94–100 |year= 2011 |pmid= 21040914 |doi= 10.1016/j.atherosclerosis.2010.10.004 |display-authors=etal}} *{{cite journal |vauthors=Rzehak P, Thijs C, Standl M |title=Variants of the FADS1 FADS2 gene cluster, blood levels of polyunsaturated fatty acids and eczema in children within the first 2 years of life. |journal=PLOS ONE |volume=5 |issue= 10 |article-number= e13261 |year= 2010 |pmid= 20948998 |doi= 10.1371/journal.pone.0013261 |pmc=2952585|bibcode=2010PLoSO...513261R |display-authors=etal|doi-access=free }} *{{cite journal |vauthors=Lattka E, Illig T, Heinrich J, Koletzko B |title=FADS gene cluster polymorphisms: important modulators of fatty acid levels and their impact on atopic diseases. |journal=J. Nutr. Nutr. |volume=2 |issue= 3 |pages= 119–28 |year= 2009 |pmid= 19776639 |doi= 10.1159/000235559 |s2cid=17077710 |url=https://epub.ub.uni-muenchen.de/16661/1/10_1159_000235559.pdf }} *{{cite journal |vauthors=Lattka E, Illig T, Heinrich J, Koletzko B |title=Do FADS genotypes enhance our knowledge about fatty acid related phenotypes? |journal=Clin Nutr |volume=29 |issue= 3 |pages= 277–87 |year= 2010 |pmid= 19948371 |doi= 10.1016/j.clnu.2009.11.005 }} *{{cite journal |vauthors=Mathias RA, Vergara C, Gao L |title=FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. |journal=J. Lipid Res. |volume=51 |issue= 9 |pages= 2766–74 |year= 2010 |pmid= 20562440 |doi= 10.1194/jlr.M008359 |doi-access=free |pmc=2918459|display-authors=etal}} *{{cite journal |vauthors=Koletzko B, Lattka E, Zeilinger S |title=Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children. |journal=Am. J. Clin. Nutr. |volume=93 |issue= 1 |pages= 211–9 |year= 2011 |pmid= 21106917 |doi= 10.3945/ajcn.110.006189 |display-authors=etal|doi-access=free }} *{{cite journal |vauthors=Bokor S, Dumont J, Spinneker A |title=Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. |journal=J. Lipid Res. |volume=51 |issue= 8 |pages= 2325–33 |year= 2010 |pmid= 20427696 |doi= 10.1194/jlr.M006205 |doi-access=free |pmc=2903808|display-authors=etal}} *{{cite journal |vauthors=Glaser C, Heinrich J, Koletzko B |title=Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism. |journal=Metab. Clin. Exp. |volume=59 |issue= 7 |pages= 993–9 |year= 2010 |pmid= 20045144 |doi= 10.1016/j.metabol.2009.10.022 }} *{{cite journal |vauthors=Steer CD, Davey Smith G, Emmett PM |title=FADS2 polymorphisms modify the effect of breastfeeding on child IQ. |journal=PLOS ONE |volume=5 |issue= 7 |article-number= e11570 |year= 2010 |pmid= 20644632 |doi= 10.1371/journal.pone.0011570 |pmc=2903485|bibcode=2010PLoSO...511570S |display-authors=etal|doi-access=free }} *{{cite journal |vauthors=Merino DM, Ma DW, Mutch DM |title=Genetic variation in lipid desaturases and its impact on the development of human disease. |journal=Lipids Health Dis |volume=9 |article-number= 63 |year= 2010 |pmid= 20565855 |doi= 10.1186/1476-511X-9-63 |pmc=2914715 |doi-access=free }} *{{cite journal |vauthors=Kröger J, Zietemann V, Enzenbach C |title=Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. |journal=Am. J. Clin. Nutr. |volume=93 |issue= 1 |pages= 127–42 |year= 2011 |pmid= 20980488 |doi= 10.3945/ajcn.110.005447 |display-authors=etal|doi-access=free }} *{{cite book |vauthors=Koletzko B, Demmelmair H, Schaeffer L |title=Genetically determined variation in polyunsaturated fatty acid metabolism may result in different dietary requirements. |journal=Nestle Nutrition Workshop Series. Paediatric Programme |volume=62 |pages= 35–44; discussion 44–49 |year= 2008 |pmid= 18626191 |doi= 10.1159/000146246 |display-authors=etal |series=Nestlé Nutrition Workshop Series: Pediatric Program |isbn=978-3-8055-8553-8 |url=http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-35257-7 }} *{{cite journal |author1=Segrè AV |title=Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. |journal=PLOS Genet. |volume=6 |issue= 8 |article-number= e1001058|year= 2010 |pmid= 20714348 |doi= 10.1371/journal.pgen.1001058 |pmc=2920848|display-authors=etal |doi-access=free }} * {{cite journal |vauthors=Zietemann V, Kröger J, Enzenbach C, Jansen E, Fritsche A, Weikert C, Boeing H, Schulze MB | title = Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study | journal = Br. J. Nutr. | volume = 104 | issue = 12 | pages = 1748–59 |date=December 2010 | pmid = 20691134 | doi = 10.1017/S0007114510002916 | s2cid = 21849126 | doi-access = free }} *{{cite journal |vauthors=Park MH, Kim N, Lee JY, Park HY |title=Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population. |journal=J. Med. Genet. |volume=48 |issue= 1 |pages= 10–5 |year= 2011 |pmid= 20972250 |doi= 10.1136/jmg.2010.081000 |s2cid=28391289 }} * {{cite journal |vauthors=Lu Y, Feskens EJ, Dollé ME, Imholz S, Verschuren WM, Müller M, Boer JM | title = Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study | journal = Am. J. Clin. Nutr. | volume = 92 | issue = 1 | pages = 258–65 |date=July 2010 | pmid = 20484448 | doi = 10.3945/ajcn.2009.29130 | doi-access = free }} *{{cite journal |vauthors=Bailey SD, Xie C, Do R |title=Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. |journal=Diabetes Care |volume=33 |issue= 10 |pages= 2250–3 |year= 2010 |pmid= 20628086 |doi= 10.2337/dc10-0452 |pmc=2945168|display-authors=etal}} {{refend}}

{{Dioxygenases}} {{Enzymes}} {{Portal bar|Biology|border=no}}

Category:EC 1.14.19