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Pathway Description
Phosphatidylcholine Biosynthesis PC(14:0/15:0)
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-09
Last Updated: 2023-10-22
Phosphatidylcholines (PC) are a class of phospholipids that incorporate a phosphocholine headgroup into a diacylglycerol backbone. They are the most abundant phospholipid in eukaryotic cell membranes and has both structural and signalling roles. In eukaryotes, there exist two phosphatidylcholine biosynthesis pathways: the Kennedy pathway and the methylation pathway. The Kennedy pathway begins with the direct phosphorylation of free choline into phosphocholine followed by conversion into CDP-choline and subsequently phosphatidylcholine. It is the major synthesis route in animals. The methylation pathway involves the 3 successive methylations of phosphatidylethanolamine to form phosphatidylcholine. The first reaction of the Kennedy pathway involves the cytosol-localized enzyme choline/ethanolamine kinase catalyzing the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. A parallel Kennedy pathway forms phosphatidylethanolamine from ethanolamine - the only difference being a different enzyme, ethanolamine-phosphate cytidylyltransferase, catalyzing the second step. Phosphatidylethanolamine is also synthesized from phosphatidylserine in the mitochondrial membrane by phosphatidylserine decarboxylase. Phosphatidylethanolamine funnels into the methylation pathway in which phosphatidylethanolamine N-methyltransferase (PEMT) then catalyzes three sequential N-methylation steps to convert phosphatidylethanolamine to phosphatidylcholine. PEMT uses S-adenosyl-L-methionine as a methyl donor.
References
Phosphatidylcholine Biosynthesis PC(14:0/15:0) References
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Kalmar GB, Kay RJ, Lachance A, Aebersold R, Cornell RB: Cloning and expression of rat liver CTP: phosphocholine cytidylyltransferase: an amphipathic protein that controls phosphatidylcholine synthesis. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6029-33. doi: 10.1073/pnas.87.16.6029.
Pubmed: 2166941
MacDonald JI, Kent C: Baculovirus-mediated expression of rat liver CTP:phosphocholine cytidylyltransferase. Protein Expr Purif. 1993 Feb;4(1):1-7. doi: 10.1006/prep.1993.1001.
Pubmed: 8381041
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Zborowski J, Dygas A, Wojtczak L: Phosphatidylserine decarboxylase is located on the external side of the inner mitochondrial membrane. FEBS Lett. 1983 Jun 27;157(1):179-82. doi: 10.1016/0014-5793(83)81141-7.
Pubmed: 6862014
Dygas A, Zborowski J: Effect of triton X-100 on the activity and solubilization of rat liver mitochondrial phosphatidylserine decarboxylase. Acta Biochim Pol. 1989;36(2):131-41.
Pubmed: 2618245
Cui Z, Vance JE, Chen MH, Voelker DR, Vance DE: 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. 1993 Aug 5;268(22):16655-63.
Pubmed: 8344945
This pathway was generated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Generated from SMP0086499
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 SMP0014218
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