Acyl-CoA dehydrogenases
Acyl-CoA dehydrogenases are enzymes that catalyze formation of a double bond between C2 (α) and C3 (β) of the acyl-CoA thioester substrates. [20] Flavin adenine dinucleotide (FAD) is a required co-factor.
| Fatty acid desaturase, type 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Fatty_acid_desaturase-1 | ||||||||
| Pfam | PF00487 | ||||||||
| InterPro | IPR005804 | ||||||||
| OPM superfamily | 431 | ||||||||
| OPM protein | 4zyo | ||||||||
| |||||||||
| Fatty acid desaturase, type 2 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Fatty_acid_desaturase-2 | ||||||||
| Pfam | PF03405 | ||||||||
| InterPro | IPR005067 | ||||||||
| |||||||||
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 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. [1]
Two subgroups of desaturases are recognized:
For example, Δ6 desaturation introduces a double bond between carbons 6 and 7 of linoleic acid (LA C18H32O2; 18:2-n6) and α-linolenic acid (ALA: C18H30O2; 18:3-n3), creating γ-linolenic acid (GLA: C18H30O2,18:3-n6) and stearidonic acid (SDA: C18H28O2; 18:4-n3) respectively. [2]
In the biosynthesis of essential fatty acids, an elongase alternates with various desaturases (for example, Δ6-desaturase) repeatedly inserts an ethyl group, then forms a double bond.
Desaturases have diiron active sites reminiscent of methane monooxygenase. These enzymes are O2-dependent, consistent with their function as either hydroxylation or oxidative dehydrogenation. [3]
Desaturases produce unsaturated fatty acids. Unsaturated fatty acids help maintain structure and function of membranes. Highly unsaturated fatty acids (HUFAs) are incorporated into phospholipids and participate in cell signaling. [4]
Unsaturated fatty acids and their derived fats increase the fluidity of membranes. [5]
Fatty acid desaturase appear in all organisms: for example, bacteria, fungus, plants, animals and humans. [6] Four desaturases occur in humans: Δ9-desaturase, Δ6-desaturase, Δ5-desaturase, and Δ4-desaturase. [4]
Δ9-desaturase, also known as stearoyl-CoA desaturase-1, is used to synthesize oleic acid, a monounsaturated, ubiquitous component of all cells in the human body, and the major fatty acid in mammalian adipose triglycerides, and also used for phospholipid and cholesteryl ester synthesis. [4] Δ9-desaturase produces oleic acid (C18H34O2; 18:1-n9) by desaturating stearic acid (SA: C18H36O2; 18:0), a saturated fatty acid either synthesized in the body from palmitic acid (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 acids (synthesized from α-linolenic acid); arachidonic acid and adrenic acid (synthesized from linoleic acid). 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. [7]
Synthesis of LC-PUFAs in humans and many other eukaryotes starts with:
* Linoleic acid (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 → arachidonic acid (AA: C20H32O2; 20:4-n6) → also endocannabinoids.
* α-Linolenic acid (ALA: C18H30O2; 18:3-n3) → Δ6-desaturation → stearidonic acid (SDA: C18H28O2; 18:4-n3) and/or → Δ6-specific elongase → eicosatetraenoic acid (ETA: C20H32O2; 20:4-n3) → Δ5-desaturase → eicosapentaenoic acid (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 eicosatetraenoic acid (ETA: C20H32O2; 20:4-n3; omega-3 arachidonic acid) [8] and arachidonic acid (AA: C20H32O2; 20:4-n6) to eicosapentaenoic acid (EPA: C20H30O2; 20:5-n3), respectively. [2]
* Anandamide (AEA: C22H37 NO 2; 20:4,n-6) is an N-acylethanolamine resulting from the formal condensation of the carboxyl group of arachidonic acid (AA: C20H32O2; 20:4-n6) with the amino group of ethanolamine (C2H7 NO), bind preferably to CB1 receptors. [10]
* 2-Arachidonoylglycerol (2-AG: C23H38O4; 20:4-n6) is an endogenous agonist of the cannabinoid receptors (CB1 and CB2), and the physiological ligand for the cannabinoid CB2 receptor. [11] It is an ester formed from omega-6-arachidonic acid (AA: C20H32O2; 20:4-n6) and glycerol (C3H8O3). [12]
Vertebrates are unable to synthesize polyunsaturated fatty acids because they do not have the necessary fatty acid desaturases to "convert oleic acid (18:1n-9) into linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3)". [7] 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, [13] can provide all the protein, essential fatty acids, and dietary fiber necessary for human survival for one day, [14] as their absence has been found responsible for the development of a wide range of diseases such as metabolic disorders, [15] cardiovascular disorders, inflammatory processes, viral infections, certain types of cancer and autoimmune disorders. [16]
Human fatty acid desaturases include: DEGS1; DEGS2; FADS1; FADS2; FADS3; FADS6; SCD4; SCD5
Δ-desaturases are represented by two distinct families which do not seem to be evolutionarily related.
Family 1 includes Stearoyl-CoA desaturase-1 (SCD) (EC 1.14.19.1). [17]
Family 2 is composed of:
Acyl-CoA dehydrogenases are enzymes that catalyze formation of a double bond between C2 (α) and C3 (β) of the acyl-CoA thioester substrates. [20] Flavin adenine dinucleotide (FAD) is a required co-factor.
N-acylethanolamine (NAE)
In chemistry, particularly 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, from 4 to 28. Fatty acids are a major component of the lipids in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells.
A triglyceride is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates, as well as vegetable fat. They are also present in the blood to enable the bidirectional transference of adipose fat and blood glucose from the liver, and are a major component of human skin oils.
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, 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.
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the Neo-Latin word arachis (peanut), but peanut oil does not contain any arachidonic 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. In chemical terms, oleic acid is classified as a monounsaturated omega-9 fatty acid, abbreviated with a lipid number of 18:1 cis-9, and a main product of Δ9-desaturase. It has the formula CH3−(CH2)7−CH=CH−(CH2)7−COOH. The name derives from the Latin word oleum, which means oil. It is the most common fatty acid in nature. The salts and esters of oleic acid are called oleates. It is part of many oils and thus used in a lot of artificial food, as well as for soap.
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(CH
2)
7CH=CHCH
2CH=CH(CH
2)
4CH
3. 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.
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.
Stearidonic acid (SDA: C18H28O2; 18:4, n-3) is an ω-3 fatty acid, sometimes called moroctic acid. It is biosynthesized from alpha-linolenic acid (ALA: C18H30O2; 18:3, n-3) by the enzyme delta-6-desaturase, that removes two hydrogen (H) atoms from a fatty acid, creating a carbon/carbon double bonding, via an oxygen requiring unsaturation. SDA also act as precursor for the rapid synthesis of longer chain fatty acids, called N-acylethanolamine (NAEs), involved in many important biological processes. Natural sources of this fatty acid are the seed oils of hemp, blackcurrant, corn gromwell, and Echium plantagineum, and the cyanobacterium Spirulina. SDA can also be synthesized in a lab. A GMO soybean source is approved by the European Food Safety Authority.
There are many fatty acids found in nature. The two essential fatty acids are omega-3 and omega-6, which are necessary for good human health. However, the effects of the ω-3 (omega-3) and ω-6 (omega-6) essential fatty acids (EFAs) are characterized by their interactions. The interactions between these two fatty acids directly effect the signaling pathways and biological functions like inflammation, protein synthesis, neurotransmitters in our brain, and metabolic pathways in the human body.
Calendic acid is an unsaturated fatty acid, named for the pot marigold, from which it is obtained. It is chemically similar to the conjugated linoleic acids; laboratory work suggests it may have similar in vitro bioactivities.
In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine to form triglycerides, the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed. Phospholipids form the bulk of the lipid bilayers that make up cell membranes and surrounds the organelles within the cells.
Mead acid is an omega-9 fatty acid, first characterized by James F. Mead. As with some other omega-9 polyunsaturated fatty acids, animals can make Mead acid de novo. Its elevated presence in the blood is an indication of essential fatty acid deficiency. Mead acid is found in large quantities in cartilage.
In enzymology, an acyl-[acyl-carrier-protein] desaturase (EC 1.14.19.2) is an enzyme that catalyzes the chemical reaction
In enzymology, a 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
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.
Sapienic acid is a fatty acid that is a major component of human sebum. Unique to humans, it takes its scientific name from the root sapiens. The equivalent fatty acid in mouse sebum is palmitoleic acid. Sapienic acid salts, esters, anion, and conjugate base are known as sapienates.
Sciadonic acid, also known as eicosatrienoic acid, is a polyunsaturated fatty acid. In regard to its structure, 5Z,11Z,14Z-eicosa-5,11,14-trienoic acid has 3 double bonds in the 5, 11, and 14 positions all of which are in the cis- conformation. It is further classified as Δ5-fatty, and an omega-6 acid due to the methylene interrupted double bond at carbon-5 and a final double bond 6 carbons away from the methylene tail of the hydrocarbon. Sciadonic acid is a naturally occurring compound and has been found to play a role as a plant metabolite, commonly found in pine nut oil. Furthermore, there have been propositions of several health applications for sciadonic acid as an anti-inflammatory agent. Sharing close structural similarity to arachidonic acid, sciadonic acid acts as a replacement phospholipid in the corresponding biochemical pathways.