Biology:Fatty acid desaturase

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Fatty acid desaturase, type 1
Identifiers
SymbolFatty_acid_desaturase-1
PfamPF00487
InterProIPR005804
OPM superfamily431
OPM protein4zyo
Fatty acid desaturase, type 2
Identifiers
SymbolFatty_acid_desaturase-2
PfamPF03405
InterProIPR005067

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:

  • 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.[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.

Mechanism and function

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]

Role in human metabolism

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: C22H37NO2; 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 (C2H7NO), 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

Classification

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:

  • Bacterial fatty acid desaturases.
  • Plant stearoyl-acyl-carrier-protein desaturase (EC 1.14.19.1),[18] 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,[19] 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 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.

Beta-Oxidation1.svg

See also

N-acylethanolamine (NAE)

References

  1. ↑ "Transgenic biosynthesis of polyunsaturated fatty acids: a sustainable biochemical engineering approach for making essential fatty acids in plants and animals". Chemical Reviews 113 (5): 3799–3814. May 2013. doi:10.1021/cr300007p. PMID 23421688. 
  2. ↑ 2.0 2.1 "Long-chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties". Food Science & Nutrition 2 (5): 443–463. September 2014. doi:10.1002/fsn3.121. PMID 25473503. 
  3. ↑ "Dioxygen Activation by Enzymes Containing Binuclear Non-Heme Iron Clusters". Chemical Reviews 96 (7): 2625–2658. November 1996. doi:10.1021/cr9500489. PMID 11848839. 
  4. ↑ 4.0 4.1 4.2 "Structure, function, and dietary regulation of Δ6, Δ5, and Δ9 desaturases". Annual Review of Nutrition 24: 345–376. 2004. doi:10.1146/annurev.nutr.24.121803.063211. PMID 15189125. 
  5. ↑ "The Fluidity of a Lipid Bilayer Depends on Its Composition". Molecular Biology of the Cell (4th ed.). New York: Garland Science. 2002. p. 588. ISBN 978-0-8153-3218-3. https://www.ncbi.nlm.nih.gov/books/NBK26871/#A1874. 
  6. ↑ "Structure and expression of fatty acid desaturases". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1394 (1): 3–15. October 1998. doi:10.1016/S0005-2760(98)00091-5. PMID 9767077. 
  7. ↑ 7.0 7.1 "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. December 2001. doi:10.1073/pnas.251516598. PMID 11724940. Bibcode: 2001PNAS...9814304H. 
  8. ↑ "8,11,14,17-Eicosatetraenoic acid" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/3080584. 
  9. ↑ "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. May 2001. doi:10.1073/pnas.101119098. PMID 11353819. Bibcode: 2001PNAS...98.6402B. 
  10. ↑ "Anandamide" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/5281969. 
  11. ↑ "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" (in English). The Journal of Biological Chemistry 275 (1): 605–612. January 2000. doi:10.1074/jbc.275.1.605. PMID 10617657. 
  12. ↑ "2-Arachidonoylglycerol" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/5282280. 
  13. ↑ "Variability in Seed Traits in a Collection of Cannabis sativa L. Genotypes". Frontiers in Plant Science 7: 688. 2016-05-20. doi:10.3389/fpls.2016.00688. PMID 27242881. 
  14. ↑ "Hemp Seed Protein" (in en-US). https://innvista.com/health/foods/hemp/hemp-seed-protein/. 
  15. ↑ "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. March 2022. doi:10.3390/ijms23063083. PMID 35328503. 
  16. ↑ "Gamma‐linolenic and stearidonic acids: Purification and upgrading of C18‐PUFA oils" (in en). European Journal of Lipid Science and Technology 112 (10): 1068–1081. 2010. doi:10.1002/ejlt.200900294. ISSN 1438-7697. 
  17. ↑ "Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase". The Journal of Biological Chemistry 264 (25): 14755–61. September 1989. doi:10.1016/S0021-9258(18)63763-9. PMID 2570068. https://www.jbc.org/content/264/25/14755.full.pdf. 
  18. ↑ "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. March 1991. doi:10.1073/pnas.88.6.2510. PMID 2006187. Bibcode: 1991PNAS...88.2510S. 
  19. ↑ "Enhancement of chilling tolerance of a cyanobacterium by genetic manipulation of fatty acid desaturation". Nature 347 (6289): 200–3. September 1990. doi:10.1038/347200a0. PMID 2118597. Bibcode: 1990Natur.347..200W. 
  20. ↑ "Structure and mechanism of action of the acyl-CoA dehydrogenases". FASEB Journal 9 (9): 718–25. June 1995. doi:10.1096/fasebj.9.9.7601336. PMID 7601336. 
This article incorporates text from the public domain Pfam and InterPro: IPR005067



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