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|
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, [Datko88c, Datko88b, Bolognese00, Williams94, Tasseva04]). Additional routes were reported in animals and yeast (see 1 and 5 below, [Schneider79, Boumann05] and reviewed in [Li08c, 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 [Schneider79].
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 18.104.22.168).
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 [Li08c]).
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].
Variants: phosphatidylcholine biosynthesis II , phosphatidylcholine biosynthesis III , phosphatidylcholine biosynthesis IV , phosphatidylcholine biosynthesis V , phosphatidylcholine biosynthesis VI , phosphatidylcholine biosynthesis VII , phospholipid remodeling (phosphatidylcholine, yeast)
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
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
Schneider79: 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
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
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
Jones98b: 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
Kim98b: 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
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
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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