This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: CDP-diacylglycerol biosynthesis
|Superclasses:||Biosynthesis → Fatty Acid and Lipid Biosynthesis → Phospholipid Biosynthesis → CDP-diacylglycerol Biosynthesis|
Phospholipids are important membrane components. Most of the phospholipids belong to the category of phosphoglycerides. The simplest phosphoglycerides, which are known as phosphatidates, are composed of a glycerol molecule attached to two fatty acids and one phosphate group. The carboxyl group of each fatty acid is esterified to the hydroxyl groups on carbon-1 and carbon-2 of the glycerol molecule, while the phosphate group is attached to carbon-3 by an ester link. Phosphatidates are precursors for many phosphoglycerides found in animals, plants and yeast, including a phosphatidylinositol, an L-1-phosphatidylserine, an L-1-phosphatidylethanolamine, and a cardiolipin.
As part of the synthesis of phosphoglycerides, either the phosphatidate or the modifying compound need to be activated by CTP. In some cases, the modifying compound is activated, as in the case of choline and ethanolamine, which form CDP-choline and CDP-ethanolamine, respectively. However, in the case of other compounds, such as L-serine and myo-inositol, the phosphatidate is activated first, forming a CDP-diacylglycerol, which then reacts with the modifying compound to form the phosphoglyceride.
About This Pathway
This pathway describes the biosynthesis of a CDP-diacylglycerol in eukaryotes and some Gram-negative bacteria (primarily the Gammaproteobacteria). In this pathway the production of the intermediate a 1-acyl-sn-glycerol 3-phosphate is catalyzed by the membrane-bound enzyme glycerol-3-phosphate acyltransferase. The bacterial enzyme, encoded by plsB, can utilize either an acyl-[acyl-carrier protein] or a long-chain acyl-CoA thioesters as the acyl donors, while the eukaryotic enzymes can only accept the acyl-CoA thiesters.
The addition of the second acyl moiety is catalyzed by 1-acylglycerol-3-phosphate O-acyltransferase. The bacterial enzyme, which is universally expressed in all bacteria, is encoded by plsC. As in the case of PlsB, the bacterial enzyme can utilize either a fatty acyl-[acp] or an acyl-CoA thioester as the acyl donor, while the eukaryotic enzyme can only accept acyl-CoA thioesters.
A pathway that describes the usage of fatty acyl-[acp] donors can be found at CDP-diacylglycerol biosynthesis II. It should be noted that most bacteria utilize a different route for the synthesis of a 1-acyl-sn-glycerol 3-phosphate, as described in CDP-diacylglycerol biosynthesis III.
More information can be found in superpathway of phospholipid biosynthesis II (plants).
Larson80: Larson TJ, Lightner VA, Green PR, Modrich P, Bell RM (1980). "Membrane phospholipid synthesis in Escherichia coli. Identification of the sn-glycerol-3-phosphate acyltransferase polypeptide as the plsB gene product." J Biol Chem 1980;255(19);9421-6. PMID: 6997313
Agarwal02: Agarwal AK, Arioglu E, De Almeida S, Akkoc N, Taylor SI, Bowcock AM, Barnes RI, Garg A (2002). "AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34." Nat Genet 31(1);21-3. PMID: 11967537
Agarwal06: Agarwal AK, Barnes RI, Garg A (2006). "Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase isoform 8: cloning, tissue distribution, gene structure, and enzymatic activity." Arch Biochem Biophys 449(1-2);64-76. PMID: 16620771
Aguado98: Aguado B, Campbell RD (1998). "Characterization of a human lysophosphatidic acid acyltransferase that is encoded by a gene located in the class III region of the human major histocompatibility complex." J Biol Chem 273(7);4096-105. PMID: 9461603
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Bayan89: Bayan N, Therisod H (1989). "Evidence for interactions of acyl carrier protein with glycerol-3-phosphate acyltransferase, an inner membrane protein of Escherichia coli." FEBS Lett 1989;255(2);330-4. PMID: 2676605
Beisson07: Beisson F, Li Y, Bonaventure G, Pollard M, Ohlrogge JB (2007). "The acyltransferase GPAT5 is required for the synthesis of suberin in seed coat and root of Arabidopsis." Plant Cell 19(1);351-68. PMID: 17259262
Bell74: Bell RM (1974). "Mutants of Escherichia coli defective in membrane phospholipid synthesis: macromolecular synthesis in an sn-glycerol 3-phosphate acyltransferase Km mutant." J Bacteriol 117(3);1065-76. PMID: 4591941
Bell75: Bell RM, Cronan JE (1975). "Mutants of Escherichia coli defective in membrane phospholipid synthesis. Phenotypic suppression of sn-glycerol-3-phosphate acyltransferase Km mutants by loss of feedback inhibition of the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 250(18);7153-8. PMID: 240817
Brown02a: Brown AP, Carnaby S, Brough C, Brazier M, Slabas AR (2002). "Limnanthes douglasii lysophosphatidic acid acyltransferases: immunological quantification, acyl selectivity and functional replacement of the Escherichia coli plsC gene." Biochem J 364(Pt 3);795-805. PMID: 12049644
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
Clark80a: Clark D, Lightner V, Edgar R, Modrich P, Cronan JE, Bell RM (1980). "Regulation of phospholipid biosynthesis in Escherichia coli. Cloning of the structural gene for the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 255(2);714-7. PMID: 6985897
Cronan74: Cronan JE, Bell RM (1974). "Mutants of Escherichia coli defective in membrane phospholipid synthesis: mapping of the structural gene for L-glycerol 3-phosphate dehydrogenase." J Bacteriol 118(2);598-605. PMID: 4597451
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