Contents

Linoleoyl-CoA desaturase

Class of enzymes

It has been suggested that this article should be split into a new article titled EC 1.14.19.3. (discuss) (January 2024)

FADS2
Identifiers
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
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q12.2 Start 61,792,980 bp[1] End 61,867,354 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 A Start 10,040,129 bp[2] End 10,079,110 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal cortex ganglionic eminence ventricular zone stromal cell of endometrium skin of thigh amygdala hypothalamus islet of Langerhans smooth muscle tissue Top expressed in otic vesicle adrenal gland saccule otic placode habenula dentate gyrus of hippocampal formation granule cell optic nerve dorsomedial hypothalamic nucleus right kidney ventricular zone More reference expression data BioGPS n/a
Gene ontology Molecular function stearoyl-CoA 9-desaturase activity oxidoreductase activity linoleoyl-CoA desaturase activity Cellular component integral component of membrane integral component of plasma membrane endoplasmic reticulum membrane membrane endoplasmic reticulum Biological process unsaturated fatty acid biosynthetic process alpha-linolenic acid metabolic process linoleic acid metabolic process fatty acid biosynthetic process lipid metabolism fatty acid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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
View/Edit Human View/Edit Mouse

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 ${\displaystyle \rightleftharpoons }$ gamma-linolenoyl-CoA + A + 2 H₂O

The three substrates of this enzyme are linoleoyl-CoA, an electron acceptorAH₂, 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[edit]

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 acidtogamma-linolenic acid (GLA), and palmitic acidtosapienic 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 tissueastriglycerides.

Agonists and inhibiting factors[edit]

This section needs expansion with: citations. You can help by adding to it. (December 2023)

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[edit]

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[edit]

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[edit]

• 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.