View source for Linoleoyl-CoA desaturase

{{Short description|Class of enzymes}}
{{split|EC 1.14.19.3|date=January 2024}}
{{#invoke:Infobox_gene|getTemplateData|QID=Q18034075}}
{{enzyme
| Name = linoleoyl-CoA desaturase
| AltNames = D6D, FADS2, acyl-CoA 6-desaturase, delta-6-desaturase
| EC_number = 1.14.19.3
| CAS_number = 9014-34-0{{dead link|fix-attempted=yes|date=August 2023}}
| GO_code = 0016213
| image = 
| width = 
| caption = 
}}
'''Linoleoyl-CoA desaturase''' (also '''Delta 6 desaturase''', {{EC number|1.14.19.3}}) is an [[enzyme]] that converts between types of fatty acids, which are [[essential fatty acids|essential]] nutrients in the human body. The [[enzyme]] mainly [[catalysis|catalyzes]] the [[chemical reaction]]

:linoleoyl-CoA + AH<sub>2</sub> + O<sub>2</sub> <math>\rightleftharpoons</math> gamma-linolenoyl-CoA + A + 2 H<sub>2</sub>O

The three [[substrate (biochemistry)|substrates]] of this enzyme are [[linoleoyl-CoA]], an [[electron acceptor]] AH<sub>2</sub>, and [[dioxygen in biological reactions|O<sub>2</sub>]], whereas its three [[product (chemistry)|products]] are [[gamma-linolenoyl-CoA]], the reduction product A, and [[water|H<sub>2</sub>O]].

This enzyme belongs to the family of [[oxidoreductase]]s, specifically those acting on paired donors, with O<sub>2</sub> as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O<sub>2</sub> with oxidation of a pair of donors resulting in the reduction of O to two molecules of water.  The [[List of enzymes|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 (biochemistry)|cofactor]], [[iron]].

The enzyme is molecularly identical across all living things. It is present in [[animal]]s, [[plant]]s, [[Fungus|fungi]], and [[cyanobacteria]].<ref>{{cite journal | vauthors = Lee JM, Lee H, Kang S, Park WJ | title = Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances | journal = Nutrients | volume = 8 | issue = 1 | pages = 23 | date = January 2016 | pmid = 26742061 | pmc = 4728637 | doi = 10.3390/nu8010023 | doi-access = free }}</ref><ref name="nakamura">{{cite journal | vauthors = Nakamura MT, Nara TY | title = Structure, function, and dietary regulation of Δ6, Δ5, and Δ9 desaturases | journal = Annual Review of Nutrition | volume = 24 | pages = 345–376 | year = 2004 | pmid = 15189125 | doi = 10.1146/annurev.nutr.24.121803.063211 }}</ref>

D6D is one of the three [[fatty acid desaturase]]s present in humans along with [[FADS1|Δ-5]] and [[Stearoyl-CoA 9-desaturase|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.<ref>{{cite web | first = Dharmendra Kumar | last = Meena | name-list-style = vanc | title = HUFA and PUFA: Structures, Occurrence, Biochemistry And Their Health Benefits | url = http://aquafind.com/articles/HUFA-and-PUFA.php | work = Aquafind Aquatic Fish Database }}</ref> 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 [[α-Linolenic acid|alpha-linolenic acid]] (ALA) to [[stearidonic acid]] and tetracosatetraenoic acid to tetracosapentaenoic acid, intermediate steps in the synthesis of ALA to [[Eicosapentaenoic acid|EPA]] and of EPA to [[Docosahexanoic acid|DHA]], respectively.

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|pages=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 [[triglyceride]]s.

==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 fat|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-γ-linolenic acid|dihomo-gamma-linolenic acid]] (DGLA) and [[prostaglandin E1|prostaglandin E<sub>1</sub>]] (PGE<sub>1</sub>). It is implicated in [[semen quality|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>

== ''Toxoplasma gondii'' ==
Felines lack D6D activity in their guts and accumulate systemic linoleic acid.<ref>{{Cite journal|last1=Sinclair|first1=A. J.|last2=McLean|first2=J. G.|last3=Monger|first3=E. A.|date=1979|title=Metabolism of linoleic acid in the cat|journal=Lipids|language=en|volume=14|issue=11|pages=932–936|doi=10.1007/BF02533508|pmid=513981|s2cid=4023638 |issn=1558-9307}}</ref> 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.<ref>{{Cite journal |vauthors=Martorelli Di Genova B, Wilson SK, Dubey JP, Knoll LJ |date=August 2019 |title=Intestinal delta-6-desaturase activity determines host range for ''Toxoplasma'' sexual reproduction |journal=PLOS Biology |volume=17 |issue=8 |page=e3000364 |doi=10.1371/journal.pbio.3000364 |doi-access=free |pmid=31430281 |pmc=6701743}}</ref>

==References==
{{reflist|1}}
* {{cite journal | vauthors = Okayasu T, Nagao M, Ishibashi T, Imai Y | date = 1981 | title = Purification and partial characterization of linoleoyl-CoA desaturase from rat liver microsomes | journal = Arch. Biochem. Biophys.  | volume = 206 | pages = 21–28  | pmid = 7212717 | doi = 10.1016/0003-9861(81)90061-8 | issue = 1 }}

{{Dioxygenases}}
{{Enzymes}}
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[[Category:EC 1.14.19]]
[[Category:Iron enzymes]]
[[Category:Enzymes of unknown structure]]