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De Novo Triacylglycerol Biosynthesis TG(18:2(9Z,12Z)/20:1(11Z)/20:4(5Z,8Z,11Z,14Z))
Last Updated: 2019-11-03
A triglyceride (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 other animals, 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 (Wikipedia). De novo biosynthesis of triglycerides is also known as the phosphatidic acid pathway, and it is mainly associated with the liver and adipose tissue. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). The next three steps are localized to the endoplasmic reticulum membrane. The enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. Next, magnesium-dependent phosphatidate phosphatase catalyzes the conversion of phosphatidic acid into diacylglycerol. Last, the enzyme diacylglycerol O-acyltransferase synthesizes triacylglycerol from diacylglycerol and a fatty acyl-CoA.
De Novo Triacylglycerol Biosynthesis TG(18:2(9Z,12Z)/20:1(11Z)/20:4(5Z,8Z,11Z,14Z)) References
Lehner R, Kuksis A: Biosynthesis of triacylglycerols. Prog Lipid Res. 1996;35(2):169-201.Pubmed: 8944226
Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.Pubmed: 16305752
Mistry DH, Medrano JF: Cloning and localization of the bovine and ovine lysophosphatidic acid acyltransferase (LPAAT) genes that codes for an enzyme involved in triglyceride biosynthesis. J Dairy Sci. 2002 Jan;85(1):28-35. doi: 10.3168/jds.S0022-0302(02)74049-6.Pubmed: 11860120
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.Pubmed: 19393038
Grisart B, Coppieters W, Farnir F, Karim L, Ford C, Berzi P, Cambisano N, Mni M, Reid S, Simon P, Spelman R, Georges M, Snell R: Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res. 2002 Feb;12(2):222-31. doi: 10.1101/gr.224202.Pubmed: 11827942
Winter A, Kramer W, Werner FA, Kollers S, Kata S, Durstewitz G, Buitkamp J, Womack JE, Thaller G, Fries R: Association of a lysine-232/alanine polymorphism in a bovine gene encoding acyl-CoA:diacylglycerol acyltransferase (DGAT1) with variation at a quantitative trait locus for milk fat content. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9300-5. doi: 10.1073/pnas.142293799. Epub 2002 Jun 20.Pubmed: 12077321
This pathway was generated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
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