Fatty acid desaturase

Fatty acid desaturase, type 1
Identifiers
SymbolFatty_acid_desaturase-1
PfamPF00487
InterProIPR005804
OPM superfamily431
OPM protein4zyo
Available protein structures:
PDB  IPR005804 PF00487 (ECOD; PDBsum)  
AlphaFold
Fatty acid desaturase, type 2
Identifiers
SymbolFatty_acid_desaturase-2
PfamPF03405
InterProIPR005067
Available protein structures:
PDB  IPR005067 PF03405 (ECOD; PDBsum)  
AlphaFold

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 linoleic acid, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid.[1]

Two nomenclatures are used to indicate the position of desaturation:

  • 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) to create larger molecules. The elongase extends the molecule by two methylene groups (-CH2-CH2-) while the desaturase forms double bonds.

Classification

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

Family 1 uses cytochrome b5 as the electron donor. This family includes all animal and fungal fatty acid desaturases, including the human types listed below.[3] This type is also found in plants and bacteria. Desaturases of this family are largely membrane-bound. They process acyl-CoA and acyl-lipid substrates.[4] The Pfam domain (PF00487) also matches the closely related alkane 1-monooxygenases, a reflection of the catalytic flexibility of the FADS-like superfamily. The sphingolipid α-hydroxylases also belong to the same superfamily.[5]

Family 2 uses ferredoxin as the electron donor. This family is found in bacteria and plant plastids. Desaturases of this family are largely soluble and process acyl‐lipid and acyl‐ACP (acyl carrier protein) substrates.[4] Notable examples include:

  • Plant stearoyl-(acyl-carrier-protein) 9-desaturase (EC 1.14.19.2),[6] 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. This enzyme is derived from endosymbiosis of the chloroplast.
  • Cyanobacterial DesA (EC 1.14.19.45),[7] 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.

Mechanism and function

Type 1 desaturases have diiron active sites reminiscent of methane monooxygenase. These enzymes are O2-dependent, consistent with their function as either hydroxylation or oxidative dehydrogenation.[8]

All 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.[9] Unsaturated fatty acids and their derived fats increase the fluidity of membranes.[10]

Role in human metabolism

Fatty acid desaturase appear in all organisms: for example, bacteria, fungus, plants, animals and humans.[11] Four desaturase activities occur in humans: Δ9-desaturase, Δ6-desaturase, Δ5-desaturase, and Δ4-desaturase.[9]

Synthesis of LC-PUFAs in humans and many other eukaryotes starts with:

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)".[12] Linoleic acid (LA) and α-linolenic acid (ALA) are essential for human health and development, and should therefore be consumed in the diet. 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. Not all of these are included in the "canonical" path of fatty acid metabolism above: some of these prefer to work on sphingolipid tails instead of fatty acid-CoA molecules, others are not expressed in the right place to take on a significant part of the work.

Endocannabinoid system

In non-human metabolism

The desaturase activities found in non-vertebrate animals, bacteria, and plants provide the essential fatty acids that humans cannot make.[2]

Oleic acid (18:1n-9) is converted into linoleic acid (18:2n-6) by a Δ12 desaturase, and then into α-linolenic acid (18:3n-3) by a Δ15 desaturase.[2]

By a Δ17-desaturase (also not found in humans), gamma-linolenic acid (GLA; 18:3 n-6) can be further converted to stearidonic acid (SDA: C18H28O2; 18:4-n3), dihomo-gamma-linolenic acid (DHGLA/DGLA; 20:3-n6) to eicosatetraenoic acid (ETA; 20:4 n-3; omega-3 arachidonic acid)[20] and arachidonic acid (AA; 20:4 n-6) to eicosapentaenoic acid (EPA; 20:5 n-3), respectively.[2]

Industrial relevance

The ACP desaturases play a critical role in the biosynthesis of unsaturated fatty acids in plants, and are very specific to their substrates.[21] A common theme in recent research has been to identify uncommon desaturases in various plants and isolate their genetic code.[22][23] This can then be inserted into model cells (such as Escherichia coli) and up-regulated through metabolic engineering to skew the composition of oils produced by the model cells.[24]

Manipulation of desaturase genes enable or enhance the production of many economically valuable nutraceutical ingredients, such as:

  • By copying (mainly CoA) desaturase genes from other organisms into plants, scientists have successfully produced plants that accumulate DHA and EPA in their oils, creating a new source of these nutrients.[25] Some of these oils have received approval for human use while others are approved for animal feed (to increase the nutrition of the meat produced by these animals). This is important because the world does not produce enough of the two fatty acids for consumption by the entire human population at recommended levels.[26]
  • Overexpression of a Δ5 desaturase increases EPA production in the diatom Phaeodactylum. This technique can potentially be applied to microalgae, which is currently used to make DHA and EPA.[27]
  • Mucor circinelloides, a model organism used in the industry to produce γ-linolenic acid (GLA), can have a D6E(GLELO) gene overexpressed to produce dihomo-γ-linolenic acid (DGLA). Further adding a delta-17 desaturase from another organism makes it able to accumulate eicosatetraenoic acid (20:4 n-3).[28]

Other desaturating enzymes

The following enzymes also "desaturate" substrates but are not conventionally considered desaturases.

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.[29] Flavin adenine dinucleotide (FAD) is a required co-factor.

See also

N-acylethanolamine (NAE)

References

  1. ^ Jiao J, Zhang Y (May 2013). "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. doi:10.1021/cr300007p. PMID 23421688.
  2. ^ a b c d 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.
  3. ^ 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.
  4. ^ a b Cerone, M; Smith, TK (November 2022). "Desaturases: Structural and mechanistic insights into the biosynthesis of unsaturated fatty acids". IUBMB life. 74 (11): 1036–1051. doi:10.1002/iub.2671. PMC 9825965. PMID 36017969.
  5. ^ Guo, X; Zhang, J; Han, L; Lee, J; Williams, SC; Forsberg, A; Xu, Y; Austin, RN; Feng, L (17 April 2023). "Structure and mechanism of the alkane-oxidizing enzyme AlkB". Nature communications. 14 (1): 2180. doi:10.1038/s41467-023-37869-z. PMID 37069165.
  6. ^ 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.
  7. ^ 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.
  8. ^ Wallar BJ, Lipscomb JD (November 1996). "Dioxygen Activation by Enzymes Containing Binuclear Non-Heme Iron Clusters". Chemical Reviews. 96 (7): 2625–2658. doi:10.1021/cr9500489. PMID 11848839.
  9. ^ a b c Nakamura MT, Nara TY (2004). "Structure, function, and dietary regulation of Δ6, Δ5, and Δ9 desaturases". Annual Review of Nutrition. 24: 345–376. doi:10.1146/annurev.nutr.24.121803.063211. PMID 15189125.
  10. ^ 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.
  11. ^ 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.
  12. ^ a b c 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. Bibcode:2001PNAS...9814304H. doi:10.1073/pnas.251516598. PMC 64677. PMID 11724940.
  13. ^ Park, HG; Park, WJ; Kothapalli, KS; Brenna, JT (September 2015). "The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells". FASEB Journal. 29 (9): 3911–9. doi:10.1096/fj.15-271783. PMC 4550368. PMID 26065859.
  14. ^ Charytoniuk T, Zywno H, Berk K, Bzdega W, Kolakowski A, Chabowski A, Konstantynowicz-Nowicka K (March 2022). "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. PMC 8948925. PMID 35328503.
  15. ^ Guil-Guerrero JL, Rincón-Cervera MÁ, Venegas-Venegas E (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. ^ 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. Bibcode:2001PNAS...98.6402B. doi:10.1073/pnas.101119098. PMC 33480. PMID 11353819.
  17. ^ "Anandamide". PubChem. U.S. National Library of Medicine. Retrieved 2022-11-28.
  18. ^ Sugiura T, Kondo S, Kishimoto S, Miyashita T, Nakane S, Kodaka T, et al. (January 2000). "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". The Journal of Biological Chemistry. 275 (1): 605–612. doi:10.1074/jbc.275.1.605. PMID 10617657.
  19. ^ "2-Arachidonoylglycerol". PubChem. U.S. National Library of Medicine. Retrieved 2022-11-28.
  20. ^ "8,11,14,17-Eicosatetraenoic acid". PubChem. U.S. National Library of Medicine. Retrieved 2022-11-27.
  21. ^ Behrouzian, B; Buist, BH (2002). "Fatty acid desaturation: variations on an oxidative theme". Current Opinion in Chemical Biology. 6 (5): 577–82. doi:10.1016/S1367-5931(02)00365-4. PMID 12413540.
  22. ^ Shanklin, J; Cahoon, E (1998). "Desaturation and related modifications of fatty acids". Annual Review of Plant Physiology and Plant Molecular Biology. 49: 611–641. doi:10.1146/annurev.arplant.49.1.611. PMID 15012248.
  23. ^ Schultz, D; Suh, M.; Ohlrogge (2000). "Stearoyl-Acyl Carrier Protein and Unusual Acyl-Acyl Carrier Protein Desaturase Activities Are Differentially Influenced by Ferredoxin". Plant Physiology. 124 (2): 681–692. doi:10.1104/pp.124.2.681. PMC 59173. PMID 11027717.
  24. ^ Cahoon, E; Mills, L.; Shanklin, J. (1996). "Modification of the fatty acid composition of Escherichia coli by coexpression of a plant acyl-acyl carrier protein desaturase and ferredoxin". Journal of Bacteriology. 178 (3): 936–939. doi:10.1128/jb.178.3.936-939.1996. PMC 177750. PMID 8550538.
  25. ^ Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O (January 2014). "Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop". The Plant Journal. 77 (2): 198–208. Bibcode:2014PlJ....77..198R. doi:10.1111/tpj.12378. PMC 4253037. PMID 24308505.
  26. ^ West, AL; Miles, EA; Lillycrop, KA; Napier, JA; Calder, PC; Burdge, GC (March 2021). "Genetically modified plants are an alternative to oily fish for providing n-3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project". Nutrition Bulletin. 46 (1): 60–68. doi:10.1111/nbu.12478. PMC 7986926. PMID 33776584.
  27. ^ He, Wenjin; Chen, Qingying; Ye, Haoying; Gao, Pingru; Wu, Bina; Meng, Wenchu; Zheng, Wenhui; Shi, Jianhua; Murong, Haien (13 December 2025). "Analysis of the Fatty Acid Desaturase Gene Family and Construction and Screening of High-EPA Transgenic Strains in Phaeodactylum tricornutum". Journal of Marine Science and Engineering. 13 (12): 2369. doi:10.3390/jmse13122369.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  28. ^ Wu, Chen; Yang, Junhuan; Li, Shaoqi; Shi, Wenyue; Xue, Futing; Liu, Qing; Naz, Tahira; Mohamed, Hassan; Song, Yuanda (12 July 2023). "Construction of Eicosatetraenoic Acid Producing Cell Factory by Genetic Engineering of Mucor circinelloides". Fermentation. 9 (7): 653. doi:10.3390/fermentation9070653.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  29. ^ 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.
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