If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Expected Taxonomic Range: Viridiplantae
Note: This is a chimeric pathway, comprising reactions from multiple organisms, and typically will not occur in its entirety in a single organism. The taxa listed here are likely to catalyze only subsets of the reactions depicted in this pathway.
Please note: This pathway does not represent a single organism. Rather, it is a super-pathway assembled from many pathways found in a variety of organisms, whose purpose is to provide an overview of the metabolic capabilities found in nature, pertaining to the biosynthesis of phosphatidylcholine.
Phosphatidylcholine is one of the major constituents of membrane phospholipids (see superpathway of phospholipid biosynthesis II (plants)). The phosphatidylcholine biosynthetic pathways vary among different organisms.
There are at least four alternative routes have been reported in plants. Two additional routes were reported in animals [Schneider79] and bacteria [Sohlenkamp00] (see pathways phosphatidylcholine biosynthesis V and phosphatidylcholine biosynthesis VI).
1) The Kennedy pathway (phosphatidylcholine biosynthesis I) depends on choline kinase and on the availability of choline.
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.
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.
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
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
Boumann04: Boumann HA, Chin PT, Heck AJ, De Kruijff B, De Kroon AI (2004). "The yeast phospholipid N-methyltransferases catalyzing the synthesis of phosphatidylcholine preferentially convert di-C16:1 substrates both in vivo and in vitro." J Biol Chem 279(39);40314-9. PMID: 15258140
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
Cui93: Cui Z, Vance JE, Chen MH, Voelker DR, Vance DE (1993). "Cloning and expression of a novel phosphatidylethanolamine N-methyltransferase. A specific biochemical and cytological marker for a unique membrane fraction in rat liver." J Biol Chem 268(22);16655-63. PMID: 8344945
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
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
Gaynor90: Gaynor PM, Carman GM (1990). "Phosphatidylethanolamine methyltransferase and phospholipid methyltransferase activities from Saccharomyces cerevisiae. Enzymological and kinetic properties." Biochim Biophys Acta 1045(2);156-63. PMID: 2198947
Hacker08: Hacker S, Sohlenkamp C, Aktas M, Geiger O, Narberhaus F (2008). "Multiple phospholipid N-methyltransferases with distinct substrate specificities are encoded in Bradyrhizobium japonicum." J Bacteriol 190(2);571-80. PMID: 17993534
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
Jones98: 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
Kim98: 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
Kodaki87: Kodaki T, Yamashita S (1987). "Yeast phosphatidylethanolamine methylation pathway. Cloning and characterization of two distinct methyltransferase genes." J Biol Chem 262(32);15428-35. PMID: 2445736
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