Fatty acid desaturase

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Fatty acid desaturase, type 1
Identifiers
SymbolFatty_acid_desaturase-1
PfamPF00487
InterProIPR005804
OPM superfamily431
OPM protein4zyo
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Fatty acid desaturase, type 2
Identifiers
SymbolFatty_acid_desaturase-2
PfamPF03405
InterProIPR005067
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

A fatty acid desaturase is an enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon/carbon double bond. These desaturases are classified as:

  • Delta - indicating that the double bond is created at a fixed position from the carboxyl end of a fatty acid 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 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.

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.[1]

In humans, Δ17-desaturase is able to turn omega 6 into omega 3 essential fatty acids.

In the biosynthesis of essential fatty acids, an elongase alternates with different desaturases (for example, Δ6desaturase) repeatedly inserting an ethyl group, then forming a double bond.

Function[edit]

Maintain structure and function of membranes within cells of the organisms above, by its esterification of highly unsaturated fatty acids (HUFAs) into phospholipids, and cell signaling.[2] This is important when temperatures changes and the membrane is under distress. The enzyme creates the double bond C-Cs which allow the membrane to become more fluid and the temperature is decreased.[3] When temperatures change, a phase transition occurs. In the case of a temperature decrease, the membrane gels and becomes solid which can result in cracks and the imbedded proteins cannot partake in conformational changes, therefore it is important to maintain membrane fluidity.[4]

Role in human metabolism[edit]

Fatty acid desaturase appear in all organisms: for example, bacteria, fungus, plants, animals and humans.[3] Four desaturases occur in humans: Δ9 desaturase, Δ6 desaturase, Δ5 desaturase, and Δ4 desaturase.[5]

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.[2] 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.[6]

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)[7] and arachidonic acid (AA: C20H32O2; 20:4-n6) to eicosapentaenoic acid (EPA: C20H30O2; 20:5-n3), respectively.[1]

* Anandamide (AEA: C22H37NO2; 20:4,n-6) is an N-acylethanolamine resulting from the formal condensation of the carboxy group of arachidonic acid (AA: C20H32O2; 20:4-n6) with the amino group of ethanolamine (C2H7NO), bind preferably to CB1 receptors.[9]

* 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.[10] It is an ester formed from omega-6-arachidonic acid (AA: C20H32O2; 20:4-n6) and glycerol (C3H8O3).[11]

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)".[6] 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,[12] can provide all the protein, essential fatty acids, and dietary fiber necessary for human survival for one day,[13] as their absence has been found responsible for the development of a wide range of diseases such as metabolic disorders,[14] cardiovascular disorders, inflammatory processes, viral infections, certain types of cancer and autoimmune disorders.[15]

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

Classification[edit]

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).[16]

Family 2 is composed of:

  • Bacterial fatty acid desaturases.
  • Plant stearoyl-acyl-carrier-protein desaturase (EC 1.14.19.1),[17] 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,[18] 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[edit]

Acyl-CoA dehydrogenases are enzymes that catalyze formation of a double bond between C2 (α) and C3 (β) of the acyl-CoA thioester substrates.[19] Flavin adenine dinucleotide (FAD) is a required co-factor.

Beta-Oxidation1.svg

See also[edit]

N-acylethanolamine (NAE)

References[edit]

  1. ^ a b Abedi E, Sahari MA (September 2014). "Long-chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties". Food Science & Nutrition. 2 (5): 443–463. doi:10.1002/fsn3.121. PMC 4237475. PMID 25473503.
  2. ^ a b Nakamura MT, Nara TY (2004). "Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases". Annual Review of Nutrition. 24: 345–376. doi:10.1146/annurev.nutr.24.121803.063211. PMID 15189125.
  3. ^ a b Los DA, Murata N (October 1998). "Structure and expression of fatty acid desaturases". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1394 (1): 3–15. doi:10.1016/S0005-2760(98)00091-5. PMID 9767077.
  4. ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). "The Fluidity of a Lipid Bilayer Depends on Its Composition". Molecular Biology of the Cell (4th ed.). New York: Garland Science. p. 588. ISBN 978-0-8153-3218-3.
  5. ^ Nakamura MT, Nara TY (2004). "Structure, function, and dietary regulation of Δ6, Δ5, and Δ9 desaturases". Annual Review of Nutrition. 24 (1): 345–76. doi:10.1146/annurev.nutr.24.121803.063211. PMID 15189125.
  6. ^ a b Hastings N, Agaba M, Tocher DR, Leaver MJ, Dick JR, Sargent JR, Teale AJ (December 2001). "A vertebrate fatty acid desaturase with Delta 5 and Delta 6 activities". Proceedings of the National Academy of Sciences of the United States of America. 98 (25): 14304–14309. doi:10.1073/pnas.251516598. PMC 64677. PMID 11724940.
  7. ^ PubChem. "8,11,14,17-Eicosatetraenoic acid". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-11-27.
  8. ^ Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, Di Marzo V (May 2001). "Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets". Proceedings of the National Academy of Sciences of the United States of America. 98 (11): 6402–6406. doi:10.1073/pnas.101119098. PMC 33480. PMID 11353819.
  9. ^ PubChem. "Anandamide". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-11-28.
  10. ^ Sugiura, Takayuki; Kondo, Sachiko; Kishimoto, Seishi; Miyashita, Tomoyuki; Nakane, Shinji; Kodaka, Tomoko; Suhara, Yoshitomo; Takayama, Hiroaki; Waku, Keizo (2000-01-07). "Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor: COMPARISON OF THE AGONISTIC ACTIVITIES OF VARIOUS CANNABINOID RECEPTOR LIGANDS IN HL-60 CELLS *". Journal of Biological Chemistry. 275 (1): 605–612. doi:10.1074/jbc.275.1.605. ISSN 0021-9258. PMID 10617657.
  11. ^ PubChem. "2-Arachidonoylglycerol". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-11-28.
  12. ^ Galasso I, Russo R, Mapelli S, Ponzoni E, Brambilla IM, Battelli G, Reggiani R (2016-05-20). "Variability in Seed Traits in a Collection of Cannabis sativa L. Genotypes". Frontiers in Plant Science. 7: 688. doi:10.3389/fpls.2016.00688. PMC 4873519. PMID 27242881.
  13. ^ "Hemp Seed Protein". Innvista. Retrieved 2022-11-28.
  14. ^ Charytoniuk, Tomasz; Zywno, Hubert; Berk, Klaudia; Bzdega, Wiktor; Kolakowski, Adrian; Chabowski, Adrian; Konstantynowicz-Nowicka, Karolina (2022-03-12). "The Endocannabinoid System and Physical Activity—A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders". International Journal of Molecular Sciences. 23 (6): 3083. doi:10.3390/ijms23063083. ISSN 1422-0067. PMC 8948925. PMID 35328503.
  15. ^ Guil‐Guerrero, José Luis; Rincón‐Cervera, Miguel Ángel; Venegas‐Venegas, Elena (2010). "Gamma‐linolenic and stearidonic acids: Purification and upgrading of C18‐PUFA oils". European Journal of Lipid Science and Technology. 112 (10): 1068–1081. doi:10.1002/ejlt.200900294. ISSN 1438-7697.
  16. ^ Kaestner KH, Ntambi JM, Kelly Jr TJ, Lane MD (September 1989). "Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase" (PDF). The Journal of Biological Chemistry. 264 (25): 14755–61. doi:10.1016/S0021-9258(18)63763-9. PMID 2570068.
  17. ^ Shanklin J, Somerville C (March 1991). "Stearoyl-acyl-carrier-protein desaturase from higher plants is structurally unrelated to the animal and fungal homologs". Proceedings of the National Academy of Sciences of the United States of America. 88 (6): 2510–4. Bibcode:1991PNAS...88.2510S. doi:10.1073/pnas.88.6.2510. PMC 51262. PMID 2006187.
  18. ^ Wada H, Gombos Z, Murata N (September 1990). "Enhancement of chilling tolerance of a cyanobacterium by genetic manipulation of fatty acid desaturation". Nature. 347 (6289): 200–3. Bibcode:1990Natur.347..200W. doi:10.1038/347200a0. PMID 2118597. S2CID 4326551.
  19. ^ Thorpe C, Kim JJ (June 1995). "Structure and mechanism of action of the acyl-CoA dehydrogenases". FASEB Journal. 9 (9): 718–25. doi:10.1096/fasebj.9.9.7601336. PMID 7601336. S2CID 42549744.
This article incorporates text from the public domain Pfam and InterPro: IPR005067