Fatty acid desaturases (also called unsaturases) are a family of enzymes that convert saturated

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

s into

unsaturated fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

s and

polyunsaturated fatty acid In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...

s. For the common fatty acids of the C18 variety, desaturases convert

stearic acid Stearic acid ( , ) is a saturated fatty acid with an 18-carbon chain. The IUPAC name is octadecanoic acid. It is a soft waxy solid with the formula . The triglyceride derived from three molecules of stearic acid is called stearin. Stearic acid ...

into

oleic acid Oleic acid is a fatty acid that occurs naturally in various animal and vegetable fats and oils. It is an odorless, colorless oil, although commercial samples may be yellowish due to the presence of impurities. In chemical terms, oleic acid is cl ...

. Other desaturases convert oleic acid into

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 ...

, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid. Two subgroups of desaturases are recognized: * Delta - indicating that the double bond is created at a fixed position from the

carboxyl 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. ...

end of a

chain. For example, Δ9-desaturase creates a double bond between the ninth and tenth carbon atom from the carboxyl end. * Omega - indicating the double bond is created at a fixed position from the

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

end of a fatty acid chain. For instance, ω3 desaturase creates a double bond between the third and fourth carbon atom from the methyl end. In other words, it creates an

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 ...

. For example, Δ6 desaturation introduces a double bond between carbons 6 and 7 of

(LA C₁₈H₃₂O₂; 18:2-n6) and

α-linolenic acid α-Linolenic acid, also known as ''alpha''-linolenic acid (ALA) (from Greek ''alpha'' denoting "first" and ''linon'' meaning flax), is an ''n''−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, ...

(ALA: C₁₈H₃₀O₂; 18:3-n3), creating ''γ''-linolenic acid (GLA: C₁₈H₃₀O₂,18:3-n6) and stearidonic acid (SDA: C₁₈H₂₈O₂; 18:4-n3) respectively. In the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

essential fatty acid Essential fatty acids, or EFAs, are fatty acids that are required by humans and other animals for normal physiological function that cannot be synthesized in the body.⁠ As they are not synthesized in the body, the essential fatty acids al ...

s, an elongase alternates with various desaturases (for example, Δ6-desaturase) repeatedly inserts an

ethyl group In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry The International Union of Pure and Applied ...

, then forms a double bond.

Mechanism and function

Desaturases have diiron

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...

s reminiscent of

methane monooxygenase Methane monooxygenase (MMO) is an enzyme capable of oxidizing the C-H bond in methane as well as other alkanes. Methane monooxygenase belongs to the class of oxidoreductase enzymes (). There are two forms of MMO: the well-studied soluble form (s ...

. These enzymes are O₂-dependent, consistent with their function as either hydroxylation or oxidative dehydrogenation. Desaturases produce unsaturated fatty acids. Unsaturated fatty acids help maintain structure and function of membranes. Highly

unsaturated fatty acids In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

( HUFAs) are incorporated into

phospholipids Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...

and participate in

cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

. Unsaturated fatty acids and their derived fats increase the fluidity of membranes.

Role in human metabolism

Fatty acid desaturase appear in all organisms: for example, bacteria, fungus, plants, animals and humans. Four desaturases occur in humans: Δ9-desaturase, Δ6-desaturase, Δ5-desaturase, and Δ4-desaturase. Δ9-desaturase, also known as

stearoyl-CoA desaturase-1 Stearoyl-CoA desaturase (Δ-9-desaturase or SCD-1) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of Monounsaturated fat, monounsaturated fatty acids (MUFAs), specifically Oleic acid, oleate and Palmito ...

, is used to synthesize

, a monounsaturated, ubiquitous component of all cells in the human body, and the major fatty acid in

mammalian A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

adipose Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

triglycerides A triglyceride (from ''wikt:tri-#Prefix, 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 oth ...

, and also used for

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

and

cholesteryl ester 300px, Cholesteryl oleate, a member of the cholesteryl ester family Cholesteryl esters are a type of dietary lipid and are ester derivatives of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl g ...

synthesis. Δ9-desaturase produces oleic acid (C₁₈H₃₄O₂; 18:1-n9) by desaturating

(SA: C₁₈H₃₆O₂; 18:0), a saturated fatty acid either synthesized in the body from

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 ...

(PA: C₁₆H₃₂O₂; 16:0) or ingested directly. Δ6 and Δ5 desaturases are required for the synthesis of highly unsaturated fatty acids such as eicosopentaenoic and

docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega−3 fatty acid that is an important component of the human brain, cerebral cortex, skin, and retina. It is given the fatty acid notation 22:6(''n''−3). It can be synthesized from alpha-linolenic acid or ...

s (synthesized from

);

arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

and adrenic acid (synthesized from

). This is a multi-stage process requiring successive actions by elongase and desaturase enzymes. The genes coding for Δ6 and Δ5 desaturase production have been located on human chromosome 11.

Synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

of LC-PUFAs in

humans Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

and many other

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

s starts with: *

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 ...

(LA: C₁₈H₃₂O₂; 18:2-n6) → Δ6-desaturation → ''γ''-linolenic acid (GLA: C₁₈H₃₀O₂; 18:3-n6) → Δ6-specific elongase (introducing two carbons) → dihomo-gamma-linolenic acid DGLA: C₂₀H₃₄O₂; 20:3-n6) → Δ5-desaturase →

(AA: C₂₀H₃₂O₂; 20:4-n6) → also endocannabinoids. *

α-Linolenic acid α-Linolenic acid, also known as ''alpha''-linolenic acid (ALA) (from Greek ''alpha'' denoting "first" and ''linon'' meaning flax), is an ''n''−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, ...

(ALA: C₁₈H₃₀O₂; 18:3-n3) → Δ6-desaturation → stearidonic acid (SDA: C₁₈H₂₈O₂; 18:4-n3) and/or → Δ6-specific elongase →

eicosatetraenoic acid Eicosatetraenoic acid (ETA) designates any straight chain tetra-unsaturated 20-carbon fatty acid. These compound are classified as polyunsaturated fatty acids (PUFA). The pure compounds, which are encountered rarely, are colorless oils. Two isomer ...

(ETA: C₂₀H₃₂O₂; 20:4-n3) → Δ5-desaturase →

eicosapentaenoic acid Eicosapentaenoic acid (EPA; also icosapentaenoic 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 wi ...

(EPA: C₂₀H₃₀O₂; 20:5-n3). By a Δ17-desaturase, gamma-linolenic acid (GLA: C₁₈H₃₀O₂; 18:3-n6) can be further converted to stearidonic acid (SDA: C₁₈H₂₈O₂; 18:4-n3), dihomo-gamma-linolenic acid (DHGLA/DGLA: C₂₀H₃₄O₂; 20:3-n6) to

(ETA: C₂₀H₃₂O₂; 20:4-n3; omega-3 arachidonic acid) and

(AA: C₂₀H₃₂O₂; 20:4-n6) to

(EPA: C₂₀H₃₀O₂; 20:5-n3), respectively. *

Fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

s with at least 20 carbons (C₂₀) and three double bonds (20:3) bind to CB1 receptors. *

Arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

(AA) is also the catalyst to the formation of the two main

endocannabinoids Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

(AEA) and

2-arachidonoylglycerol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is pres ...

(2-AG). *

Anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

(AEA: C₂₂H₃₇ NO₂; 20:4,n-6) is an ''N''-acylethanolamine resulting from the formal

condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...

of the

group of arachidonic acid (AA: C₂₀H₃₂O₂; 20:4-n6) with the

amino In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

group of

ethanolamine Ethanolamine (2-aminoethanol, monoethanolamine, ETA, or MEA) is a naturally occurring organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorl ...

(C₂H₇ NO), bind preferably to CB1 receptors. *

2-Arachidonoylglycerol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is pres ...

(2-AG: C₂₃H₃₈O₄; 20:4-n6) is an endogenous

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the cannabinoid receptors (CB1 and CB2), and the physiological

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

for the cannabinoid

CB2 receptor The cannabinoid receptor 2 (CB2), is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the ''CNR2'' gene. It is closely related to the cannabinoid receptor 1 (CB1), which is largely responsible for ...

. It is an

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

formed from omega-6-arachidonic acid (AA: C₂₀H₃₂O₂; 20:4-n6) and

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

(C₃H₈O₃). Vertebrates are unable to synthesize polyunsaturated fatty acids because they do not have the necessary fatty acid desaturases to "convert oleic acid (18:1''n''-9) into linoleic acid (18:2''n''-6) and α-linolenic acid (18:3''n''-3)". Linoleic acid (LA) and α-linolenic acid (ALA) are essential for human health and development, and should therefore be consumed by diets, like 15 ml of hemp seed oil, or/and 33 gram of hemp seed protein a day, can provide all the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

, essential fatty acids, and

dietary fiber Dietary fiber (fibre in English in the Commonwealth of Nations, Commonwealth English) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical co ...

necessary for human survival for one day, as their absence has been found responsible for the development of a wide range of diseases such as

metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the ...

s, cardiovascular disorders, inflammatory processes,

viral infections A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, ...

, certain types of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

and

autoimmune disorders An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...

. Human fatty acid desaturases include: DEGS1; DEGS2; FADS1; FADS2; FADS3; FADS6; SCD4; SCD5

Classification

Δ-desaturases are represented by two distinct families which do not seem to be evolutionarily related. Family 1 includes

Stearoyl-CoA desaturase-1 Stearoyl-CoA desaturase (Δ-9-desaturase or SCD-1) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of Monounsaturated fat, monounsaturated fatty acids (MUFAs), specifically Oleic acid, oleate and Palmito ...

(SCD) (). Family 2 is composed of: * Bacterial fatty acid desaturases. * Plant stearoyl- acyl-carrier-protein desaturase (), an enzyme that catalyzes the introduction of a double bond at the delta-9 position of steraoyl-ACP to produce oleoyl-ACP. This enzyme is responsible for the conversion of saturated fatty acids to unsaturated fatty acids in the synthesis of vegetable oils. * Cyanobacterial DesA, an enzyme that can introduce a second cis double bond at the delta-12 position of fatty acid bound to membrane glycerolipids. This enzyme is involved in chilling tolerance; the phase transition temperature of lipids of cellular membranes being dependent on the degree of unsaturation of fatty acids of the membrane lipids.

Acyl-CoA dehydrogenases

Acyl-CoA dehydrogenases are

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

that catalyze formation of a double bond between C2 (α) and C3 (β) of the acyl-CoA

thioester In organic chemistry, thioesters are organosulfur compounds with the molecular structure . They are analogous to carboxylate esters () with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix ...

substrates.

Flavin adenine dinucleotide In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which ma ...

(FAD) is a required co-factor.

References

{{InterPro content, IPR005067 Enzymes

Mechanism and function

Role in human metabolism

Classification

Acyl-CoA dehydrogenases

See also

References