Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Phospholipid Biosynthesis
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-09-15
This pathway describes the synthesis of the common phospholipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and cardiolipins. Phospholipid synthesis is mediated by two possible mechanisms: (1) A CDP-activated polar head group for attaches to the phosphate of phosphatidic acid or (2) A CDP-activated 1,2-diacylglycerol and an inactivated polar head group. The ER membrane is the primary site of phospholipid synthesis using precursors imported into the ER from the cytosol. To initiate the process, phosphatidic acid is generated by the linkage of two fatty acids associated with coenzyme A (CoA) carriers to glycerol-3-phosphate. This new molecule is inserted into the membrane where a phosphatase converts it into diacylglycerol or alternatively it is formed into phosphatidylinositol before the conversion. If the conversion into diacylglycerol occurs, the molecule has three possible fates depending on the type of polar head group attached: phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine.
At their inception, a phospholipid is composed of a saturated fatty acid and unsaturated fatty acid on the C1 and C2 carbon of the glycerol backbone respectively. With the continuous remodelling of the phospholipid bilayer, this fatty acid distribution at these carbons changes. For example, acyl group remodelling changes the presence of acyl groups on the glycerol backbone (which were initially placed there by acyl transferases) and moves it further into the membrane as a consequence of the action of phospholipase A1 (PLA1) and phospholipase A2 (PLA2). Another modifying group that is usually added are alcohol-containing groups such as serine, ethanol amine, and choline which contain positively-charged nitrogen.
References
Phospholipid Biosynthesis References
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Saito S, Goto K, Tonosaki A, Kondo H: Gene cloning and characterization of CDP-diacylglycerol synthase from rat brain. J Biol Chem. 1997 Apr 4;272(14):9503-9. doi: 10.1074/jbc.272.14.9503.
Pubmed: 9083091
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Ballas LM, Bell RM: Topography of glycerolipid synthetic enzymes. Synthesis of phosphatidylserine, phosphatidylinositol and glycerolipid intermediates occurs on the cytoplasmic surface of rat liver microsomal vesicles. Biochim Biophys Acta. 1981 Sep 24;665(3):586-95. doi: 10.1016/0005-2760(81)90274-5.
Pubmed: 6271231
Tanaka S, Nikawa J, Imai H, Yamashita S, Hosaka K: Molecular cloning of rat phosphatidylinositol synthase cDNA by functional complementation of the yeast Saccharomyces cerevisiae pis mutation. FEBS Lett. 1996 Sep 9;393(1):89-92. doi: 10.1016/0014-5793(96)00858-7.
Pubmed: 8804431
Imai A, Gershengorn MC: Regulation by phosphatidylinositol of rat pituitary plasma membrane and endoplasmic reticulum phosphatidylinositol synthase activities. A mechanism for activation of phosphoinositide resynthesis during cell stimulation. J Biol Chem. 1987 May 15;262(14):6457-9.
Pubmed: 3032971
Brown LJ, MacDonald MJ, Lehn DA, Moran SM: Sequence of rat mitochondrial glycerol-3-phosphate dehydrogenase cDNA. Evidence for EF-hand calcium-binding domains. J Biol Chem. 1994 May 20;269(20):14363-6.
Pubmed: 8182039
Muller S, Seitz HJ: Cloning of a cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase from rat liver and its regulation by thyroid hormones. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10581-5. doi: 10.1073/pnas.91.22.10581.
Pubmed: 7937996
Legay C, Bon S, Vernier P, Coussen F, Massoulie J: Cloning and expression of a rat acetylcholinesterase subunit: generation of multiple molecular forms and complementarity with a Torpedo collagenic subunit. J Neurochem. 1993 Jan;60(1):337-46. doi: 10.1111/j.1471-4159.1993.tb05856.x.
Pubmed: 8417155
Legay C, Bon S, Massoulie J: Expression of a cDNA encoding the glycolipid-anchored form of rat acetylcholinesterase. FEBS Lett. 1993 Jan 4;315(2):163-6. doi: 10.1016/0014-5793(93)81155-s.
Pubmed: 8417973
Ishii K, Oda Y, Ichikawa T, Deguchi T: Complementary DNAs for choline acetyltransferase from spinal cords of rat and mouse: nucleotide sequences, expression in mammalian cells, and in situ hybridization. Brain Res Mol Brain Res. 1990 Feb;7(2):151-9. doi: 10.1016/0169-328x(90)90092-r.
Pubmed: 2160042
Kengaku M, Misawa H, Deguchi T: Multiple mRNA species of choline acetyltransferase from rat spinal cord. Brain Res Mol Brain Res. 1993 Apr;18(1-2):71-6. doi: 10.1016/0169-328x(93)90174-n.
Pubmed: 8479291
Wu D, Hersh LB: Identification of an active site arginine in rat choline acetyltransferase by alanine scanning mutagenesis. J Biol Chem. 1995 Dec 8;270(49):29111-6. doi: 10.1074/jbc.270.49.29111.
Pubmed: 7493935
Zheng B, Chen D, Farquhar MG: MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3999-4004. doi: 10.1073/pnas.97.8.3999.
Pubmed: 10760272
Zheng B, Berrie CP, Corda D, Farquhar MG: GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1745-50. doi: 10.1073/pnas.0337605100. Epub 2003 Feb 7.
Pubmed: 12576545
Sugimoto H, Hayashi H, Yamashita S: Purification, cDNA cloning, and regulation of lysophospholipase from rat liver. J Biol Chem. 1996 Mar 29;271(13):7705-11. doi: 10.1074/jbc.271.13.7705.
Pubmed: 8631810
Portilla D, Crew MD, Grant D, Serrero G, Bates LM, Dai G, Sasner M, Cheng J, Buonanno A: cDNA cloning and expression of a novel family of enzymes with calcium-independent phospholipase A2 and lysophospholipase activities. J Am Soc Nephrol. 1998 Jul;9(7):1178-86.
Pubmed: 9644627
Abe A, Hiraoka M, Wild S, Wilcoxen SE, Paine R 3rd, Shayman JA: Lysosomal phospholipase A2 is selectively expressed in alveolar macrophages. J Biol Chem. 2004 Oct 8;279(41):42605-11. doi: 10.1074/jbc.M407834200. Epub 2004 Aug 4.
Pubmed: 15294901
Komada M, Kudo I, Mizushima H, Kitamura N, Inoue K: Structure of cDNA coding for rat platelet phospholipase A2. J Biochem. 1989 Oct;106(4):545-7. doi: 10.1093/oxfordjournals.jbchem.a122890.
Pubmed: 2606907
Komada M, Kudo I, Inoue K: Structure of gene coding for rat group II phospholipase A2. Biochem Biophys Res Commun. 1990 May 16;168(3):1059-65. doi: 10.1016/0006-291x(90)91137-h.
Pubmed: 2346480
Ishizaki J, Ohara O, Nakamura E, Tamaki M, Ono T, Kanda A, Yoshida N, Teraoka H, Tojo H, Okamoto M: cDNA cloning and sequence determination of rat membrane-associated phospholipase A2. Biochem Biophys Res Commun. 1989 Aug 15;162(3):1030-6. doi: 10.1016/0006-291x(89)90777-8.
Pubmed: 2764915
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000025
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings