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MetaCyc Pathway: phosphatidylcholine biosynthesis I

Enzyme View:

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-choline pathway

Superclasses: Biosynthesis Fatty Acids and Lipids Biosynthesis Phospholipid Biosynthesis Phosphatidylcholine Biosynthesis

Some taxa known to possess this pathway include ? : Mus musculus , Saccharomyces cerevisiae , Treponema denticola

Expected Taxonomic Range: Bacteria , Eukaryota

Summary:
General Background

Phosphatidylcholine is one of the major constituents of membrane phospholipids in eukaryotes (see phospholipid biosynthesis II). It is also present in the membranes of some bacteria. The phosphatidylcholine biosynthetic pathways vary among different organisms.

At least four alternative routes have been reported in plants (see 1-4 below, [Datko88, Datko88a, Bolognese00, Williams94a, Tasseva04]). Additional routes were reported in animals and yeast (see 1 and 5 below, [Schneider79a, Boumann05] and reviewed in [Li08, deKroon07]) and bacteria (see 1, 5, 6 and 7 below, [Sohlenkamp00, Kent04] and reviewed in [MartinezMorales03, Aktas10]).

1) The first pathway (depicted here) is a branch of the Kennedy pathway for the de novo biosynthesis of phosphatidylethanolamine (an L-1-phosphatidyl-ethanolamine) and phosphatidylcholine (a phosphatidylcholine) in eukaryotes (reviewed in [Gibellini10]) (see also phosphatidylethanolamine biosynthesis II).

2) The second pathway (phosphatidylcholine biosynthesis II) depends on three consecutive N-methylation steps that are carried out on phospho-bases, phosphoethanolamine, phospho-N-methylethanolamine, and phospho-N-dimethylethanolamine.

3) The third pathway (phosphatidylcholine biosynthesis III) depends on an initial N-methylation with phospho-base phosphoethanolamine, and followed by two downstream N-methylations on phosphatidyl-bases, phosphatidyl-N-methylethanolamine and phosphatidyl-N-dimethylethanolamine. In plants, phosphatidyl-N-methylethanolamine is believed to be derived from CDP-methylethanolamine, whereas in animals, it is a direct methylation product from phosphatidylethanolamine [Schneider79a].

4) The fourth pathway (phosphatidylcholine biosynthesis IV) depends on two N-methylations with phospho-base phosphoethanolamine and phospho-N-methylethanolamine, followed by a downstream N-methylation on phosphatidyl-base phosphatidyl-N-dimethylethanolamine.

5) The fifth pathway (phosphatidylcholine biosynthesis V) depends on the direct conversion of the phosphatidyl-base phosphatidylethanolamine to phosphatidylcholine by successive methylations.

6) The sixth pathway (phosphatidylcholine biosynthesis VI) involves a one-step direct condensation of choline with CDP-diacylglycerol to form phosphatidylcholine by the bacterial enzyme phosphatidylcholine synthase (EC 2.7.8.24).

7) The seventh pathway (phosphatidylcholine biosynthesis VII) involves bacterial acyl-CoA-dependent acyltransferases that catalyze the two-step acylation of sn-glycero-3-phosphocholine to a phosphatidylcholine [Moser14].

About This Pathway

This pathway depends on choline kinase and on the availability of choline. Animals obtain choline, an essential nutrient, primarily from the diet. They can also produce choline by conversion of phosphatidylethanolamine to phosphatidylcholine (see 5 above) followed by catabolism of phosphatidylcholine to choline (see pathway phospholipases) (reviewed in [Li08]).

The yeast Saccharomyces cerevisiae also utilizes the pathway shown here, although the methylation pathway shown in phosphatidylcholine biosynthesis V is its primary pathway. In the pathway shown here, either exogenous choline is taken up by active transport, or endogenous choline can be obtained from phosphatidylcholine turnover (reviewed in [deKroon07, Boumann05]).

It is generally accepted that plants produce phosphatidylcholine via a mixed CDP-choline and methylation pathway (in [Tasseva04]) (see pathway superpathway of phosphatidylcholine biosynthesis). Choline kinase activity has been reported from a number of plants such as Arabidopsis [Tasseva04], soybean [Monks96] and castor bean [Bligny89]. In Arabidopsis, this pathway is significant when the plants are under salt stress [Bligny89].

In addition, this pathway has been identified in the bacterium Treponema denticola [Kent04].

Superpathways: phospholipid biosynthesis II , superpathway of phosphatidylcholine biosynthesis

Variants: phosphatidylcholine biosynthesis II , phosphatidylcholine biosynthesis III , phosphatidylcholine biosynthesis IV , phosphatidylcholine biosynthesis V , phosphatidylcholine biosynthesis VI , phosphatidylcholine biosynthesis VII , phospholipid remodeling (phosphatidylcholine, yeast)

Credits:
Created 10-Jan-2003 by Hong E , Saccharomyces Genome Database
Revised 21-Jun-2011 by Fulcher CA , SRI International


References

Aktas10: Aktas M, Wessel M, Hacker S, Klusener S, Gleichenhagen J, Narberhaus F (2010). "Phosphatidylcholine biosynthesis and its significance in bacteria interacting with eukaryotic cells." Eur J Cell Biol 89(12);888-94. PMID: 20656373

Bligny89: Bligny R, Foray MF, Roby C, Douce R (1989). "Transport and phosphorylation of choline in higher plant cells. Phosphorus-31 nuclear magnetic resonance studies." J Biol Chem 264(9);4888-95. PMID: 2925673

Bolognese00: Bolognese CP, McGraw P (2000). "The isolation and characterization in yeast of a gene for Arabidopsis S-adenosylmethionine:phospho-ethanolamine N-methyltransferase." Plant Physiol 124(4);1800-13. PMID: 11115895

Boumann05: Boumann HA, de Kroon AI (2005). "The contributions of biosynthesis and acyl chain remodelling to the molecular species profile of phosphatidylcholine in yeast." Biochem Soc Trans 33(Pt 5);1146-9. PMID: 16246068

Datko88: Datko AH, Mudd SH (1988). "Phosphatidylcholine Synthesis: Differing Patterns in Soybean and Carrot." Plant Physiol 88(3);854-861. PMID: 16666397

Datko88a: Datko AH, Mudd SH (1988). "Enzymes of Phosphatidylcholine Synthesis in Lemna, Soybean, and Carrot." Plant Physiol 88(4);1338-1348. PMID: 16666464

deKroon07: de Kroon AI (2007). "Metabolism of phosphatidylcholine and its implications for lipid acyl chain composition in Saccharomyces cerevisiae." Biochim Biophys Acta 1771(3);343-52. PMID: 17010666

Gibellini10: Gibellini F, Smith TK (2010). "The Kennedy pathway--De novo synthesis of phosphatidylethanolamine and phosphatidylcholine." IUBMB Life 62(6);414-28. PMID: 20503434

Kent04: Kent C, Gee P, Lee SY, Bian X, Fenno JC (2004). "A CDP-choline pathway for phosphatidylcholine biosynthesis in Treponema denticola." Mol Microbiol 51(2);471-81. PMID: 14756787

Li08: Li Z, Vance DE (2008). "Phosphatidylcholine and choline homeostasis." J Lipid Res 49(6);1187-94. PMID: 18204095

MartinezMorales03: Martinez-Morales F, Schobert M, Lopez-Lara IM, Geiger O (2003). "Pathways for phosphatidylcholine biosynthesis in bacteria." Microbiology 149(Pt 12);3461-71. PMID: 14663079

Monks96: Monks DE, Goode JH, Dewey RE (1996). "Characterization of soybean choline kinase cDNAs and their expression in yeast and Escherichia coli." Plant Physiol 110(4);1197-205. PMID: 8934624

Moser14: Moser R, Aktas M, Narberhaus F (2014). "Phosphatidylcholine biosynthesis in Xanthomonas campestris via a yeast-like acylation pathway." Mol Microbiol 91(4);736-50. PMID: 24329598

Schneider79a: Schneider WJ, Vance DE (1979). "Conversion of phosphatidylethanolamine to phosphatidylcholine in rat liver. Partial purification and characterization of the enzymatic activities." J Biol Chem 254(10);3886-91. PMID: 438165

Sohlenkamp00: Sohlenkamp C, de Rudder KE, Rohrs V, Lopez-Lara IM, Geiger O (2000). "Cloning and characterization of the gene for phosphatidylcholine synthase." J Biol Chem 275(25);18919-25. PMID: 10858449

Tasseva04: Tasseva G, Richard L, Zachowski A (2004). "Regulation of phosphatidylcholine biosynthesis under salt stress involves choline kinases in Arabidopsis thaliana." FEBS Lett 566(1-3);115-20. PMID: 15147879

Williams94a: Williams M, Harwood JL (1994). "Alternative pathways for phosphatidylcholine synthesis in olive (Olea europaea L.) callus cultures." Biochem J 304 ( Pt 2);463-8. PMID: 7998981

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Dewey94: Dewey RE, Wilson RF, Novitzky WP, Goode JH (1994). "The AAPT1 gene of soybean complements a cholinephosphotransferase-deficient mutant of yeast." Plant Cell 6(10);1495-507. PMID: 7994181

Friesen01: Friesen JA, Park YS, Kent C (2001). "Purification and kinetic characterization of CTP:phosphocholine cytidylyltransferase from Saccharomyces cerevisiae." Protein Expr Purif 21(1);141-8. PMID: 11162399

Goode99: Goode JH, Dewey RE (1999). "Characterization of aminoalcoholphosphotransferases from Arabidopsis thaliana and soybean." Plant Physiol. Biochem. 37(6): 445-457.

Hjelmstad87: Hjelmstad RH, Bell RM (1987). "Mutants of Saccharomyces cerevisiae defective in sn-1,2-diacylglycerol cholinephosphotransferase. Isolation, characterization, and cloning of the CPT1 gene." J Biol Chem 262(8);3909-17. PMID: 3029130

Hjelmstad90: Hjelmstad RH, Bell RM (1990). "The sn-1,2-diacylglycerol cholinephosphotransferase of Saccharomyces cerevisiae. Nucleotide sequence, transcriptional mapping, and gene product analysis of the CPT1 gene." J Biol Chem 265(3);1755-64. PMID: 2153142

Hjelmstad91: Hjelmstad RH, Bell RM (1991). "sn-1,2-diacylglycerol choline- and ethanolaminephosphotransferases in Saccharomyces cerevisiae. Mixed micellar analysis of the CPT1 and EPT1 gene products." J Biol Chem 266(7);4357-65. PMID: 1847919

Hosaka89: Hosaka K, Kodaki T, Yamashita S (1989). "Cloning and characterization of the yeast CKI gene encoding choline kinase and its expression in Escherichia coli." J Biol Chem 264(4);2053-9. PMID: 2536698

Johnson92a: Johnson JE, Kalmar GB, Sohal PS, Walkey CJ, Yamashita S, Cornell RB (1992). "Comparison of the lipid regulation of yeast and rat CTP: phosphocholine cytidylyltransferase expressed in COS cells." Biochem J 285 ( Pt 3);815-20. PMID: 1323275

Jones98a: Jones PL, Willey DL, Gacesa P, Harwood JL (1998). "Isolation, characterisation and expression of a cDNA for pea cholinephosphate cytidylyltransferase." Plant Mol Biol 37(1);179-85. PMID: 9620275

Kim98a: Kim KH, Voelker DR, Flocco MT, Carman GM (1998). "Expression, purification, and characterization of choline kinase, product of the CKI gene from Saccharomyces cerevisiae." J Biol Chem 273(12);6844-52. PMID: 9506987

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

McMaster97: McMaster CR, Bell RM (1997). "CDP-choline:1,2-diacylglycerol cholinephosphotransferase." Biochim Biophys Acta 1348(1-2);100-10. PMID: 9370321

Moore83: Moore TS Jr, Price-Jones MJ, Harwood JL, (1983) "The effect of indoleacetic acid on phospholipid metabolism in pea stems." Phytochemistry (1983), 22, 2421-2425.

Morash94: Morash SC, McMaster CR, Hjelmstad RH, Bell RM (1994). "Studies employing Saccharomyces cerevisiae cpt1 and ept1 null mutants implicate the CPT1 gene in coordinate regulation of phospholipid biosynthesis." J Biol Chem 269(46);28769-76. PMID: 7961831

Mou02: Mou Z, Wang X, Fu Z, Dai Y, Han C, Ouyang J, Bao F, Hu Y, Li J (2002). "Silencing of phosphoethanolamine N-methyltransferase results in temperature-sensitive male sterility and salt hypersensitivity in Arabidopsis." Plant Cell 14(9);2031-43. PMID: 12215503

Nishida96: Nishida I, Swinhoe R, Slabas AR, Murata N (1996). "Cloning of Brassica napus CTP: phosphocholine cytidylyltransferase cDNAs by complementation in a yeast cct mutant." Plant Mol Biol 31(2);205-11. PMID: 8756587

Slack85: Slack CR, Roughan PG, Browse JA, Gardiner SE (1985). "Some properties of cholinephosphotransferase from developing safflower cotyledons." Biochim. Biophys. Acta 833; 438-448.

Tsukagoshi87: Tsukagoshi Y, Nikawa J, Yamashita S (1987). "Molecular cloning and characterization of the gene encoding cholinephosphate cytidylyltransferase in Saccharomyces cerevisiae." Eur J Biochem 169(3);477-86. PMID: 2826147

Tsukagoshi91: Tsukagoshi Y, Nikawa J, Hosaka K, Yamashita S (1991). "Expression in Escherichia coli of the Saccharomyces cerevisiae CCT gene encoding cholinephosphate cytidylyltransferase." J Bacteriol 173(6);2134-6. PMID: 1848222

Wang90: Wang X, Moore TS Jr (1990). "Phosphatidylcholine biosynthesis in castor bean endosperm. Purification and properties of cytidine 5'-triphosphate:choline-phosphate cytidylyltransferase." Plant Physiol. 93; 250-255.


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, biocyc12.