Linoleoyl-CoA desaturase (also Delta 6 desaturase, ) is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that converts between types of fatty acids, which are essential nutrients in the human body. The

mainly

catalyzes Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

the

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

:linoleoyl-CoA + AH₂ + O₂

\rightleftharpoons

gamma-linolenoyl-CoA + A + 2 H₂O The three substrates of this enzyme are linoleoyl-CoA, an

electron acceptor An electron acceptor is a chemical entity that accepts electrons transferred to it from another compound. Electron acceptors are oxidizing agents. The electron accepting power of an electron acceptor is measured by its redox potential. In the ...

AH₂, and O₂, whereas its three

products Product may refer to: Business * Product (business), an item that can be offered to a market to satisfy the desire or need of a customer. * Product (project management), a deliverable or set of deliverables that contribute to a business solution ...

are gamma-linolenoyl-CoA, the reduction product A, and H₂O. This enzyme belongs to the family of

oxidoreductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...

s, 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 A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivi ...

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 Linoleic acid (LA) is an organic compound with the formula . Both alkene groups () are cis-trans isomerism, ''cis''. It is a fatty acid sometimes denoted 18:2 (n−6) or 18:2 ''cis''-9,12. A linoleate is a salt (chemistry), salt or ester of thi ...

. It employs one cofactor,

iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...

. The enzyme is molecularly identical across all living things. It is present in

animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

, and

cyanobacteria Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteri ...

. D6D is one of the three

fatty acid desaturase Fatty acid desaturases (also called unsaturases) 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 ...

s 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 In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl group (e.g. ...

(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 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 ...

and

omega-6 Omega−6 fatty acids (also referred to as ω−6 fatty acids or ''n''−6 fatty acids) are a family of polyunsaturated fatty acids (PUFA) that share a final carbon-carbon double bond in the ''n''−6 position, that is, the sixth bond, count ...

fatty acids. In humans, it is used principally for the conversions of cis-

linoleic acid Linoleic acid (LA) is an organic compound with the formula . 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. Linoleic acid is a polyunsat ...

to gamma-linolenic acid (GLA), and

palmitic acid Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The ...

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, required for the return of unoxidized free fatty acids into

white adipose tissue White adipose tissue or white fat is one of the two types of adipose tissue found in mammals. The other kind is brown adipose tissue. White adipose tissue is composed of monolocular Adipocyte, adipocytes. In humans, the healthy body fat percent ...

triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...

Agonists and inhibiting factors

D6D is upregulated by

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

, 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. 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.

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 and

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema but the same term is also used to refer to dermatitis, the larger group of skin conditi ...

due to deficiencies in GLA and PGE₁.

''Toxoplasma gondii''

Felines lack D6D activity in their guts and accumulate systemic linoleic acid. 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.

References

* {{Portal bar, Biology, border=no EC 1.14.19 Iron enzymes Enzymes of unknown structure