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De Novo Triacylglycerol Biosynthesis
Last Updated: 2019-02-11
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. 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 References
Chen YQ, Kuo MS, Li S, Bui HH, Peake DA, Sanders PE, Thibodeaux SJ, Chu S, Qian YW, Zhao Y, Bredt DS, Moller DE, Konrad RJ, Beigneux AP, Young SG, Cao G: AGPAT6 is a novel microsomal glycerol-3-phosphate acyltransferase. J Biol Chem. 2008 Apr 11;283(15):10048-57. doi: 10.1074/jbc.M708151200. Epub 2008 Jan 31.Pubmed: 18238778
Agarwal AK, Sukumaran S, Cortes VA, Tunison K, Mizrachi D, Sankella S, Gerard RD, Horton JD, Garg A: Human 1-acylglycerol-3-phosphate O-acyltransferase isoforms 1 and 2: biochemical characterization and inability to rescue hepatic steatosis in Agpat2(-/-) gene lipodystrophic mice. J Biol Chem. 2011 Oct 28;286(43):37676-91. doi: 10.1074/jbc.M111.250449. Epub 2011 Aug 27.Pubmed: 21873652
Orland MD, Anwar K, Cromley D, Chu CH, Chen L, Billheimer JT, Hussain MM, Cheng D: Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1. Biochim Biophys Acta. 2005 Oct 15;1737(1):76-82. doi: 10.1016/j.bbalip.2005.09.003. Epub 2005 Sep 20.Pubmed: 16214399
Lehner R, Kuksis A: Biosynthesis of triacylglycerols. Prog Lipid Res. 1996;35(2):169-201.Pubmed: 8944226
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