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Chemical Compound Review

PDSP1_001402     2-[[[5-(4-amino-2-oxo- pyrimidin-1-yl)-3,4...

Synonyms: PDSP2_001386, AC1L18WS
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Disease relevance of cytidine diphosphate choline


Psychiatry related information on cytidine diphosphate choline


High impact information on cytidine diphosphate choline


Chemical compound and disease context of cytidine diphosphate choline


Biological context of cytidine diphosphate choline


Anatomical context of cytidine diphosphate choline

  • By contrast, selective accumulation of CDP-choline was the only abnormality demonstrable in proband erythrocytes [2].
  • These data demonstrate that the CDP-choline pathway alone, but not the PEMT pathway alone, can account for physiological concentrations of PC in gallbladder bile [20].
  • Remarkably, in light of widely held assumptions, the rate of phosphatidylcholine synthesis from the CDP-choline pathway was not decreased in CD hepatocytes [21].
  • In agreement with previous studies, the incorporation of [3H]choline into phosphatidylcholine via the CDP-choline pathway was stimulated 5-fold in cultures of HeLa cells following treatment with phorbol ester for 1 h [22].
  • CTP:phosphocholine cytidylyltransferase alpha is found immediately upstream cholinephosphotransferase, and it translocates from a soluble nuclear location to the nuclear membrane in response to activators of the CDP-choline pathway [23].

Associations of cytidine diphosphate choline with other chemical compounds


Gene context of cytidine diphosphate choline


Analytical, diagnostic and therapeutic context of cytidine diphosphate choline

  • Activity of cytidylyltransferase (CT), a major regulatory enzyme in the CDP-choline pathway of PC synthesis, was raised in both microsomal and cytosolic fractions (226% and 150% of controls), and there was an increase to 187% in the mass of active enzyme as determined by Western blot of microsomal protein using an antibody specific to CT [32].
  • These immunoelectron microscopy studies strongly suggest that the cellular organization of ET differs considerably from that reported recently for the corresponding enzyme in the CDP-choline pathway, CTP:phosphocholine cytidylyltransferase (Wang, Y., Sweiter, T. D., Weinhold, P. A., and Kent, C. (1993) J. Biol. Chem. 268, 5899-5904) [33].
  • Using a novel combination of stable-isotope labeling and tandem mass spectrometry, we demonstrated for the first time that choline contributed to phosphatidylcholine (PC) synthesis both as an intact choline moiety via the CDP-choline pathway and as a methyl donor via PE methylation pathway [34].
  • BACKGROUND AND PURPOSE: Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials [15].
  • CONCLUSIONS: In this animal model of ICH, treatment with citicoline significantly improved functional outcome and reduced the volume of ischemic injury surrounding the hematoma [35].


  1. Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis. Fang, M., Kearns, B.G., Gedvilaite, A., Kagiwada, S., Kearns, M., Fung, M.K., Bankaitis, V.A. EMBO J. (1996) [Pubmed]
  2. Selective accumulation of cytosol CDP-choline as an isolated erythrocyte defect in chronic hemolysis. Paglia, D.E., Valentine, W.N., Nakatani, M., Rauth, B.J. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  3. CDP-choline significantly restores phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP: phosphocholine cytidylyltransferase after stroke. Adibhatla, R.M., Hatcher, J.F., Larsen, E.C., Chen, X., Sun, D., Tsao, F.H. J. Biol. Chem. (2006) [Pubmed]
  4. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia. Kakihana, M., Fukuda, N., Suno, M., Nagaoka, A. Stroke (1988) [Pubmed]
  5. Citicoline improves verbal memory in aging. Spiers, P.A., Myers, D., Hochanadel, G.S., Lieberman, H.R., Wurtman, R.J. Arch. Neurol. (1996) [Pubmed]
  6. Chronic Administration of UMP Ameliorates the Impairment of Hippocampal-Dependent Memory in Impoverished Rats. Teather, L.A., Wurtman, R.J. J. Nutr. (2006) [Pubmed]
  7. Radioprotective effect of transferrin targeted citicoline liposomes. Suresh Reddy, J., Venkateswarlu, V., Koning, G.A. Journal of drug targeting. (2006) [Pubmed]
  8. Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes. Cohen, R.A., Browndyke, J.N., Moser, D.J., Paul, R.H., Gordon, N., Sweet, L. Cerebrovasc. Dis. (2003) [Pubmed]
  9. Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein. Cleves, A.E., McGee, T.P., Whitters, E.A., Champion, K.M., Aitken, J.R., Dowhan, W., Goebl, M., Bankaitis, V.A. Cell (1991) [Pubmed]
  10. Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function. Litvak, V., Dahan, N., Ramachandran, S., Sabanay, H., Lev, S. Nat. Cell Biol. (2005) [Pubmed]
  11. Degradation of dipalmitoyl phosphatidylcholine by isolated rat granular pneumocytes and reutilization for surfactant synthesis. Chander, A., Reicherter, J., Fisher, A.B. J. Clin. Invest. (1987) [Pubmed]
  12. Amino acid modulation of renal phosphatidylcholine biosynthesis in the rat. Havener, L.J., Toback, F.G. J. Clin. Invest. (1980) [Pubmed]
  13. Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol. Gregory, D.H., Vlahcevic, Z.R., Schatzki, P., Swell, L. J. Clin. Invest. (1975) [Pubmed]
  14. Channeling of intermediates in the CDP-choline pathway of phosphatidylcholine biosynthesis in cultured glioma cells is dependent on intracellular Ca2+. George, T.P., Cook, H.W., Byers, D.M., Palmer, F.B., Spence, M.W. J. Biol. Chem. (1991) [Pubmed]
  15. Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats. Onal, M.Z., Li, F., Tatlisumak, T., Locke, K.W., Sandage, B.W., Fisher, M. Stroke (1997) [Pubmed]
  16. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Hurtado, O., Moro, M.A., Cárdenas, A., Sánchez, V., Fernández-Tomé, P., Leza, J.C., Lorenzo, P., Secades, J.J., Lozano, R., Dávalos, A., Castillo, J., Lizasoain, I. Neurobiol. Dis. (2005) [Pubmed]
  17. Inhibitors of CDP-choline synthesis, action potential calcium channels, and stimulus-secretion coupling. de Blas, A., Adler, M., Shih, M., Chiang, P.K., Cantoni, G.L., Nirenberg, M. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  18. Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Wang, L., Magdaleno, S., Tabas, I., Jackowski, S. Mol. Cell. Biol. (2005) [Pubmed]
  19. Identification of critical residues of choline kinase A2 from Caenorhabditis elegans. Yuan, C., Kent, C. J. Biol. Chem. (2004) [Pubmed]
  20. The unique acyl chain specificity of biliary phosphatidylcholines in mice is independent of their biosynthetic origin in the liver. Agellon, L.B., Walkey, C.J., Vance, D.E., Kuipers, F., Verkade, H.J. Hepatology (1999) [Pubmed]
  21. A choline-deficient diet in mice inhibits neither the CDP-choline pathway for phosphatidylcholine synthesis in hepatocytes nor apolipoprotein B secretion. Kulinski, A., Vance, D.E., Vance, J.E. J. Biol. Chem. (2004) [Pubmed]
  22. Phosphorylation of CTP:phosphocholine cytidylyltransferase in vivo. Lack of effect of phorbol ester treatment in HeLa cells. Watkins, J.D., Kent, C. J. Biol. Chem. (1990) [Pubmed]
  23. The major sites of cellular phospholipid synthesis and molecular determinants of Fatty Acid and lipid head group specificity. Henneberry, A.L., Wright, M.M., McMaster, C.R. Mol. Biol. Cell (2002) [Pubmed]
  24. Expression of phosphatidylethanolamine N-methyltransferase-2 cannot compensate for an impaired CDP-choline pathway in mutant Chinese hamster ovary cells. Houweling, M., Cui, Z., Vance, D.E. J. Biol. Chem. (1995) [Pubmed]
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  26. Does rat liver Golgi have the capacity to synthesize phospholipids for lipoprotein secretion? Vance, J.E., Vance, D.E. J. Biol. Chem. (1988) [Pubmed]
  27. Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway. DeLong, C.J., Shen, Y.J., Thomas, M.J., Cui, Z. J. Biol. Chem. (1999) [Pubmed]
  28. Nte1p-mediated deacylation of phosphatidylcholine functionally interacts with Sec14p. Murray, J.P., McMaster, C.R. J. Biol. Chem. (2005) [Pubmed]
  29. Phosphatidylcholine biosynthesis in Saccharomyces cerevisiae. Regulatory insights from studies employing null and chimeric sn-1,2-diacylglycerol choline- and ethanolaminephosphotransferases. McMaster, C.R., Bell, R.M. J. Biol. Chem. (1994) [Pubmed]
  30. Phosphorylation of Saccharomyces cerevisiae CTP synthetase at Ser424 by protein kinases A and C regulates phosphatidylcholine synthesis by the CDP-choline pathway. Choi, M.G., Park, T.S., Carman, G.M. J. Biol. Chem. (2003) [Pubmed]
  31. A role for phospholipase D (Pld1p) in growth, secretion, and regulation of membrane lipid synthesis in yeast. Sreenivas, A., Patton-Vogt, J.L., Bruno, V., Griac, P., Henry, S.A. J. Biol. Chem. (1998) [Pubmed]
  32. Enhancement of mdr2 gene transcription mediates the biliary transfer of phosphatidylcholine supplied by an increased biosynthesis in the pravastatin-treated rat. Carrella, M., Feldman, D., Cogoi, S., Csillaghy, A., Weinhold, P.A. Hepatology (1999) [Pubmed]
  33. Ultrastructural localization of CTP:phosphoethanolamine cytidylyltransferase in rat liver. van Hellemond, J.J., Slot, J.W., Geelen, M.J., van Golde, L.M., Vermeulen, P.S. J. Biol. Chem. (1994) [Pubmed]
  34. Disruption of choline methyl group donation for phosphatidylethanolamine methylation in hepatocarcinoma cells. DeLong, C.J., Hicks, A.M., Cui, Z. J. Biol. Chem. (2002) [Pubmed]
  35. Citicoline treatment for experimental intracerebral hemorrhage in mice. Clark, W., Gunion-Rinker, L., Lessov, N., Hazel, K. Stroke (1998) [Pubmed]
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