Linoleoyl-CoA desaturase

Last updated
FADS2
Identifiers
Aliases FADS2 , D6D, DES6, FADSD6, LLCDL2, SLL0262, TU13, fatty acid desaturase 2
External IDs OMIM: 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 Mb Chr 19: 10.04 – 10.08 Mb
PubMed search [3] [4]
Wikidata
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linoleoyl-CoA desaturase
Identifiers
EC no. 1.14.19.3
CAS no. 9014-34-0[ permanent dead link ]
Alt. namesD6D, FADS2, acyl-CoA 6-desaturase, delta-6-desaturase
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins

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

Contents

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%) [ citation needed ].

D6D activity slows with age, suggested by reductions in GLA and subsequent metabolites. [10] [11] 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. [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]

Related Research Articles

Omega−3 fatty acids, also called Omega−3 oils, ω−3 fatty acids or n−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chemical structure. They are widely distributed in nature, being important constituents of animal lipid metabolism, and they play an important role in the human diet and in human physiology. The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA can be found in plants, while DHA and EPA are found in algae and fish. Marine algae and phytoplankton are primary sources of omega−3 fatty acids. DHA and EPA accumulate in fish that eat these algae. Common sources of plant oils containing ALA include walnuts, edible seeds, and flaxseeds as well as hempseed oil, while sources of EPA and DHA include fish and fish oils, and algae oil.

Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health, but cannot synthesize them.

α-Linolenic acid Chemical compound

α-Linolenic acid, also known as alpha-Linolenic acid (ALA), is an n−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, walnuts, chia, hemp, and many common vegetable oils.

gamma-Linolenic acid or GLA is an n−6, or omega-6, fatty acid found primarily in seed oils. When acting on GLA, arachidonate 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid to leukotrienes is inhibited.

Linoleic acid (LA) is an organic compound with the formula HOOC(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are cis. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 cis-9,12. A linoleate is a salt or ester of this acid.

<span class="mw-page-title-main">Eicosapentaenoic acid</span> Chemical compound

Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-carbon chain and five cis double bonds; the first double bond is located at the third carbon from the omega end.

<span class="mw-page-title-main">Docosahexaenoic acid</span> Chemical compound

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk, fatty fish, fish oil, or algae oil.

<span class="mw-page-title-main">Resolvin</span> Class of chemical compounds

Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as from two isomers of docosapentaenoic acid (DPA), one omega-3 and one omega-6 fatty acid. As autacoids similar to hormones acting on local tissues, resolvins are under preliminary research for their involvement in promoting restoration of normal cellular function following the inflammation that occurs after tissue injury. Resolvins belong to a class of polyunsaturated fatty acid (PUFA) metabolites termed specialized proresolving mediators (SPMs).

<span class="mw-page-title-main">Polyunsaturated fat</span> Type of fatty acid defined by molecular bonds

In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid, which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsaturated fatty acids are essentials. Polyunsaturated fatty acids are precursors to and are derived from polyunsaturated fats, which include drying oils.

Dihomo-γ-linolenic acid (DGLA) is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 (ω−6). DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product of γ-linolenic acid. GLA, in turn, is a desaturation product of linoleic acid. DGLA is made in the body by the elongation of GLA, by an efficient enzyme which does not appear to suffer any form of (dietary) inhibition. DGLA is an extremely uncommon fatty acid, found only in trace amounts in animal products.

Fatty acid desaturases are a family of enzymes that convert saturated fatty acids into unsaturated fatty acids and polyunsaturated fatty acids. For the common fatty acids of the C18 variety, desaturases convert stearic acid into oleic acid. Other desaturases convert oleic acid into linolenic acid, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid.

<span class="mw-page-title-main">Essential fatty acid interactions</span>

There are many fatty acids found in nature. Two types of fatty acids considered essential for human health are the omega-3 and omega-6 types. These two essential fatty acids are necessary for some cellular signalling pathways and are involved in mediating inflammation, protein synthesis, and metabolic pathways in the human body.

<span class="mw-page-title-main">Acyl-(acyl-carrier-protein) desaturase</span> Class of enzymes

In enzymology, an acyl-[acyl-carrier-protein] desaturase (EC 1.14.19.2) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Stearoyl-CoA 9-desaturase</span> Class of enzymes

Stearoyl-CoA desaturase (Δ-9-desaturase) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of monounsaturated fatty acids (MUFAs), specifically oleate and palmitoleate from stearoyl-CoA and palmitoyl-CoA. Oleate and palmitoleate are major components of membrane phospholipids, cholesterol esters and alkyl-diacylglycerol. In humans, the enzyme is encoded by the SCD gene.

<span class="mw-page-title-main">FADS2</span> Protein-coding gene in the species Homo sapiens

Fatty acid desaturase 2 (FADS2) is an enzyme that in humans is encoded by the FADS2 gene.

<span class="mw-page-title-main">FADS1</span> Protein-coding gene in the species Homo sapiens

Fatty acid desaturase 1 (FADS1) is an enzyme that in humans is encoded by the FADS1 gene.

<span class="mw-page-title-main">CYP4F8</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene.

<span class="mw-page-title-main">Oxylipin</span> Class of lipids

Oxylipins constitute a family of oxygenated natural products which are formed from fatty acids by pathways involving at least one step of dioxygen-dependent oxidation. Oxylipins are derived from polyunsaturated fatty acids (PUFAs) by COX enzymes (cyclooxygenases), by LOX enzymes (lipoxygenases), or by cytochrome P450 epoxygenase.

Delta12-fatty-acid desaturase (EC 1.14.19.6, Delta12 fatty acid desaturase, Delta12(omega6)-desaturase, oleoyl-CoA Delta12 desaturase, Delta12 desaturase, Delta12-desaturase) is an enzyme with systematic name acyl-CoA,hydrogen donor:oxygen Delta12-oxidoreductase. This enzyme catalyses the following chemical reaction

In general, cognitive support diets are formulated to include nutrients that have a known role in brain development, function and/or maintenance, with the goal of improving and preserving mental processes such as attentiveness, short-term and long-term memory, learning, and problem solving. Currently, there is very little conclusive research available regarding cat cognition as standardized tests for evaluating cognitive ability are less established and less reliable than cognitive testing apparatus used in other mammalian species, like dogs. Much of what is known about feline cognition has been inferred from a combination of owner-reported behaviour, brain necropsies, and comparative cognitive neurology of related animal models. Cognition claims appear primarily on kitten diets which include elevated levels of nutrients associated with optimal brain development, although there are now diets available for senior cats that include nutrients to help slow the progression of age-related changes and prevent cognitive decline. Cognition diets for cats contain a greater portion of omega-3 fatty acids, especially docosahexaenoic acid (DHA) as well as eicosapentaenoic acid (EPA), and usually feature a variety of antioxidants and other supporting nutrients thought to have positive effects on cognition.

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. 17 (8): 688580. doi: 10.1101/688580 . PMC   6701743 . PMID   31430281.
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