In biochemistry, docosanoids are

signaling molecules In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

made by the metabolism of twenty-two-carbon fatty acids (EFAs), especially the

omega-3 fatty acid 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 chem ...

Docosahexaenoic acid 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-lin ...

(DHA) (i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z'',19''Z''-docosahexaenoic acid) by

lipoxygenase Lipoxygenases () are a family of (non-heme) iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into cell signaling agents that serve diverse roles as aut ...

cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as pr ...

, and

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

enzymes. Other docosanoids are metabolites of n-3 docosapentaenoic acid (i.e. 7''Z'',10''Z'',13''Z'',16''Z'',19''Z''-docosahexaenoic acid), n-6 DHA (i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z''-docosahexaenoic acid, and docosatetraenoic acid (i.e. 7''Z'',10''Z'',13''Z'',16''Z''-docosatetraenoic acid, DTA, or adrenic acid). Prominent docosanoid metabolites of DHA and n-3 DHA are members of the specialized proresolving mediator class of

polyunsaturated fatty acid Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...

metabolites that possess potent anti-

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

, tissue healing, and other activities (see

specialized proresolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...

Prominent docosanoids

Specialized proresolving mediator docosanoids

Potently bioactive agents of the specialized proresolving mediator class include: *DHA-derived

Resolvins Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. As autacoids similar ...

(Rv's) of the D series: RvD1, RvD2, RvD3, RvD4, RvD5, RvD6, AT-RvD1, AT-RvD2, AT-RvD3, AT-RvD4, AT-RvD5, and AT-RvD6 (see specialized proresolving mediators#DHA-derived Resolvins). *n-3 DPA-derived Rvs of the D series (RvD1_n-3, RvD2_n-3, and RvDD1_n-3) and the T series (RvT1, TvT2, RvT3, and RvT4) (see specialized proresolving mediators#n-3 DPA-derived resolvins). *DHA-derived

Neuroprotectin Neuroprotectin D1 (NPD1) (10''R'',17''S''-dihydroxy-4''Z'',7''Z'',11''E'',13''E'',15''Z'',19''Z''-docosahexaenoic acid) also known as Protectin D1 (PD1) is a docosanoid derived from the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA ...

s, also termed protectins: PD1, PDX, 17-epi PD1, and 10-epi-DHA1 (see specialized proresolving mediators#DHA-derived protectins/neuroprotectins). *n-3 DPA derived protectins: RD1_n-3 and RvD1_n-3 (see specialized proresolving mediators#n-3 DPA-derived resolvins)(see DPA-derived protectins/neuroprotectins. *DHA derived Maresins: MaR1, MaR2, 7-epi-Mar1, Mar-L1, and Mar-L2 (see specialized proresolving mediators#DHA-derived Maresins). *n-3 DPA-derived maresins: Mar1_n-3, Mar2_n-3, and Mar3_n-3 (see specialized proresolving mediators#n-3 DPA-derived maresins). These DHA metabolites possess anti-

and tissue-protection activities in animal models of inflammatory diseases; they are proposed to inhibit innate immune responses and thereby to protect from and to resolve a wide range of inflammatory responses in animals and humans. These metabolites are also proposed to contribute to the anti-inflammatory and other beneficial effects of dietary omega-3 fatty acids by being metabolized to them.

Neurofuran docosanoids

DHA can be converted non-enzymatically by free radical-mediated peroxidation to 8 different

neurofuran Neurofurans are 22-carbon compounds formed nonenzymatically by free radical mediated peroxidation of docosahexaenoic acid (DHA), an ω-3 essential fatty acid. The neurofurans are similar to the isofurans and are formed under similar conditions of ...

regio

isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...

termed neuroprostanes and neurofuranes including 4-, 7-, 10-, 11-, 13-, 14-, 17-, and 20-series neurofurans/neuroporstanes for a total of 128 different racemic compounds. The most studied DHA-derived of these products are members of the 4-series, neurofuran 4-F_αneuroprostane and 4(''RS'')-ST-Δ6-8-neurofurane. These metabolites have been used mainly as

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

s of

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

that are formed in nerve tissues of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

Hydroxy-docosanoids

Cells metabolize DHA to 17''S''-hydroperoxy-4''Z'',7''Z'',10''Z'',13''Z'',15''E'',19''Z''-docahexaenoicacid acid (17-HpDHA) and then rapidly reduce this hydroperoxide to 17''S''-hydroxy-4''Z'',7''Z'',10''Z'',13''Z'',15''E'',19''Z''-docahexaenoicacid acid (17-HDHA) and similarly metabolize DHA to 13''S''-hydroperoxy-4''Z'',7''Z'',10''Z'',14''Z'',16''Z'',19''Z''-docahexaenoicacid acid (13-HpDHA) and then to 13''S''-hydroxy-4''Z'',7''Z'',10''Z'',14''Z'',16''Z'',19''Z''-docahexaenoicacid acid (13-HDHA). 17-HDHA exhibits potent in vitro as well as in vivo (animal model) anti-inflammatory activity while 17-HpDHA and to a lesser extent 17-HDHA inhibit the growth of cultured human breast cancer cells. Other SPM docosanoids, e.g. RvD1 and RvD2, have anti-growth effects against cancer cells in animal models.

Oxo-docosanoids

Cells can metabolize DHA to products that possess an oxo (i.e. ketone) residue. These products include 13-oxo-DHA (termed EFOXD6) and 17-oxo-DHA (termed 18-EFOXD6). Both oxo metabolites possess anti-inflammatory activity as assesses in in vitro systems (see Specialized proresolving mediators#Oxo-DHA and oxo-DPA metabolites).

DTA-derived docosanoids

Cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as pr ...

and

Cytochrome P450 oxidase Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

act upon

Docosatetraenoic acid Docosatetraenoic acid designates any straight chain 22:4 fatty acid. (''See'' essential fatty acid for nomenclature.) One isomer is of particular interest: * all-''cis''-7,10,13,16-docosatetraenoic acid is an ω-6 fatty acid with the common nam ...

to produce dihomoprostaglandins and dihomo-epoxyeicosatrienoic acids and dihomo-

EET "Eet" is a song from Regina Spektor's fifth studio album, ''Far (album), Far''. It was released as the album's second official single in October 2009. In Europe it was released as a digital download on November 27, 2009. Music video A Viral vide ...

s.{{cite journal , journal= Am J Physiol Heart Circ Physiol , date =May 2007, volume=292, issue=5, pages=H2265–74 , title=Metabolism of adrenic acid to vasodilatory 1alpha,1beta-dihomo-epoxyeicosatrienoic acids by bovine coronary arteries. , vauthors=Yi XY, Gauthier KM, Cui L, Nithipatikom K, Falck JR, Campbell WB , pmid=17209008 , doi=10.1152/ajpheart.00947.2006

References

Cell biology Immunology Metabolic pathways Fatty acids