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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:04:34 UTC
HMDB IDHMDB01413
Secondary Accession NumbersNone
Metabolite Identification
Common NameCiticoline
DescriptionCiticoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Once absorbed, citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product. (PMID: 17171187 ).
Structure
Thumb
Synonyms
ValueSource
[2-CYTIDYLATE-o'-phosphonyloxyl]-ethyl-trimethyl-ammoniumChEBI
CDP-ColinaChEBI
CiticolinaChEBI
CiticolineChEBI
CiticolinumChEBI
Citidin difosfato de colinaChEBI
CyticholineChEBI
CytidindiphosphocholinChEBI
Cytidine 5'-(choline diphosphate)ChEBI
Cytidine 5'-(cholinyl pyrophosphate)ChEBI
Cytidine 5'-diphosphocholineChEBI
Cytidine 5'-diphosphoric cholineChEBI
[2-CYTIDYLic acid-o'-phosphonyloxyl]-ethyl-trimethyl-ammoniumGenerator
Cytidine 5'-(choline diphosphoric acid)Generator
Cytidine 5'-(cholinyl pyrophosphoric acid)Generator
AudesHMDB
CerebHMDB
Choline 5'-cytidine diphosphateHMDB
Choline cytidine diphosphateHMDB
CiticholineHMDB
CitidolineHMDB
CitifarHMDB
ColiteHMDB
CorenalinHMDB
CyscholinHMDB
Cytidine 5'-diphosphate cholineHMDB
Cytidine 5-diphosphate-trihydrogenHMDB
Cytidine choline diphosphateHMDB
Cytidine diphosphate cholineHMDB
Cytidine diphosphate choline esterHMDB
Cytidine diphosphocholineHMDB
Cytidine diphosphorylcholineHMDB
Cytidine-5' diphosphocholineHMDB
Cytidine-5'-pyrophosphate-hydroxycholineHMDB
CytidolineHMDB
DifosfocinHMDB
Emicholine FHMDB
EnsignHMDB
HaocolinHMDB
HornbestHMDB
NeucolisHMDB
NicholinHMDB
NicolinHMDB
NiticolinHMDB
P-Hydroxide[2-(trimethylammonio)ethyl] esterHMDB
ReaginHMDB
RecofnanHMDB
RecognanHMDB
RexortHMDB
SintoclarHMDB
SomazinaHMDB
SomazineHMDB
SuncholinHMDB
Chemical FormulaC14H26N4O11P2
Average Molecular Weight488.324
Monoisotopic Molecular Weight488.107330718
IUPAC Name{2-[({[(2R,3S,4R,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl phosphonato)oxy]ethyl}trimethylazanium
Traditional Namecdp-choline
CAS Registry Number987-78-0
SMILES
C[N+](C)(C)CCOP([O-])(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=CC(N)=NC1=O
InChI Identifier
InChI=1S/C14H26N4O11P2/c1-18(2,3)6-7-26-30(22,23)29-31(24,25)27-8-9-11(19)12(20)13(28-9)17-5-4-10(15)16-14(17)21/h4-5,9,11-13,19-20H,6-8H2,1-3H3,(H3-,15,16,21,22,23,24,25)/t9-,11-,12-,13-/m1/s1
InChI KeyInChIKey=RZZPDXZPRHQOCG-OJAKKHQRSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrimidine ribonucleoside diphosphates. These are pyrimidine ribobucleotides with diphosphate group linked to the ribose moiety.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleotides
Sub ClassPyrimidine ribonucleotides
Direct ParentPyrimidine ribonucleoside diphosphates
Alternative Parents
Substituents
  • Pyrimidine ribonucleoside diphosphate
  • Phosphocholine
  • N-glycosyl compound
  • Glycosyl compound
  • Organic pyrophosphate
  • Monosaccharide phosphate
  • Monoalkyl phosphate
  • Pyrimidone
  • Choline
  • Aminopyrimidine
  • Imidolactam
  • Alkyl phosphate
  • Pyrimidine
  • Primary aromatic amine
  • Phosphoric acid ester
  • Organic phosphoric acid derivative
  • Organic phosphate
  • Monosaccharide
  • Hydropyrimidine
  • Saccharide
  • Heteroaromatic compound
  • Quaternary ammonium salt
  • Oxolane
  • Secondary alcohol
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic salt
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
Biofunction
  • Component of Aminophosphonate metabolism
  • Component of Glycerophospholipid metabolism
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility7.99 mg/mLALOGPS
logP-1.4ALOGPS
logP-6.2ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)1.85ChemAxon
pKa (Strongest Basic)-0.52ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area213.5 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity113.58 m3·mol-1ChemAxon
Polarizability42.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0006-0001900000-a9f38ff6b185b45f04b3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-03e9-0590000000-b021677d064d65810ee0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-0900000000-7570bbb10dd9fa288442View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-000i-0000900000-8b411373962b073b4d22View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positivesplash10-000i-0001900000-6e7cc437ad79eb13c032View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-01qi-1932200000-9c3803cefdd9c6285a7cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-004i-6505900000-3d534aab6e40915c3642View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-004i-6505900000-fc13e5ad403e7faf8218View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid LocationsNot Available
Tissue Location
  • Brain
  • Erythrocyte
  • Intestine
Pathways
NameSMPDB LinkKEGG Link
Phospholipid BiosynthesisSMP00025map00564
Plasmalogen SynthesisSMP00479Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022608
KNApSAcK IDNot Available
Chemspider ID13207
KEGG Compound IDC00307
BioCyc IDCDP-CHOLINE
BiGG ID1485298
Wikipedia LinkCiticoline
NuGOwiki LinkHMDB01413
Metagene LinkHMDB01413
METLIN ID6229
PubChem Compound13804
PDB IDCDC
ChEBI ID16436
References
Synthesis ReferenceFujio, Tatsuro. New production method of useful substances using ATP regeneration system. Kiraru Tekunoroji no Shintenkai (2001), 187-198.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Porciatti V, Schiavi C, Benedetti P, Baldi A, Campos EC: Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects. Curr Eye Res. 1998 Feb;17(2):141-8. [9523091 ]
  2. Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF: Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002 May;161(3):248-54. Epub 2002 Mar 22. [12021827 ]
  3. Alvarez XA, Mouzo R, Pichel V, Perez P, Laredo M, Fernandez-Novoa L, Corzo L, Zas R, Alcaraz M, Secades JJ, Lozano R, Cacabelos R: Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999 Nov;21(9):633-44. [10669911 ]
  4. Laurence AD, Layton M, Duley JA, Simmonds HA: Elevated erythrocyte CDP-choline levels associated with beta-thalassaemia in patients with transfusion independent anaemia. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1265-7. [15571243 ]
  5. Friedman D, Cycowicz YM, Bersick M: The late negative episodic memory effect: the effect of recapitulating study details at test. Brain Res Cogn Brain Res. 2005 May;23(2-3):185-98. Epub 2004 Nov 21. [15820627 ]
  6. Alvarez XA, Laredo M, Corzo D, Fernandez-Novoa L, Mouzo R, Perea JE, Daniele D, Cacabelos R: Citicoline improves memory performance in elderly subjects. Methods Find Exp Clin Pharmacol. 1997 Apr;19(3):201-10. [9203170 ]
  7. Paglia DE, Valentine WN, Nakatani M, Rauth BJ: Selective accumulation of cytosol CDP-choline as an isolated erythrocyte defect in chronic hemolysis. Proc Natl Acad Sci U S A. 1983 May;80(10):3081-5. [6574471 ]
  8. Hayashida K: [Usefulness of SPECT images in helping radiologists understand brain diseases] Nippon Igaku Hoshasen Gakkai Zasshi. 2001 Apr;61(5):208-14. [11398344 ]
  9. Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE: Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report. Psychopharmacology (Berl). 1999 Feb;142(2):132-8. [10102764 ]
  10. Weiss GB: Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci. 1995;56(9):637-60. [7869846 ]
  11. Petersen A, Borregaard N: A family with chronic haemolysis and selective accumulation of erythrocyte CDP-choline. Leukemia. 1997 Aug;11(8):1373-6. [9264395 ]
  12. de la Morena E: Efficacy of CDP-choline in the treatment of senile alterations in memory. Ann N Y Acad Sci. 1991;640:233-6. [1776744 ]
  13. Secades JJ, Lorenzo JL: Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol. 2006 Sep;28 Suppl B:1-56. [17171187 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Controls phosphatidylcholine synthesis.
Gene Name:
PCYT1B
Uniprot ID:
Q9Y5K3
Molecular weight:
40228.99
Reactions
Cytidine triphosphate + Phosphorylcholine → Pyrophosphate + Citicolinedetails
General function:
Involved in catalytic activity
Specific function:
Controls phosphatidylcholine synthesis.
Gene Name:
PCYT1A
Uniprot ID:
P49585
Molecular weight:
41730.67
Reactions
Cytidine triphosphate + Phosphorylcholine → Pyrophosphate + Citicolinedetails
General function:
Involved in catalytic activity
Specific function:
Bidirectional lipid cholinephosphotransferase capable of converting phosphatidylcholine (PC) and ceramide to sphingomyelin (SM) and diacylglycerol (DAG) and vice versa. Direction is dependent on the relative concentrations of DAG and ceramide as phosphocholine acceptors. Directly and specifically recognizes the choline head group on the substrate. Also requires two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. Does not function strictly as a SM synthase. Required for cell growth
Gene Name:
SGMS2
Uniprot ID:
Q8NHU3
Molecular weight:
42279.8
General function:
Involved in catalytic activity
Specific function:
Bidirectional lipid cholinephosphotransferase capable of converting phosphatidylcholine (PC) and ceramide to sphingomyelin (SM) and diacylglycerol (DAG) and vice versa. Direction is dependent on the relative concentrations of DAG and ceramide as phosphocholine acceptors. Directly and specifically recognizes the choline head group on the substrate. Also requires two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. Does not function strictly as a SM synthase. Suppresses BAX-mediated apoptosis and also prevents cell death in response to stimuli such as hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. May protect against cell death by reversing the stress-inducible increase in levels of proapoptotic ceramide. Required for cell growth
Gene Name:
SGMS1
Uniprot ID:
Q86VZ5
Molecular weight:
49207.3
General function:
Involved in phosphotransferase activity, for other substituted phosphate groups
Specific function:
Catalyzes phosphatidylcholine biosynthesis from CDP-choline. It thereby plays a central role in the formation and maintenance of vesicular membranes.
Gene Name:
CHPT1
Uniprot ID:
Q8WUD6
Molecular weight:
45096.535
Reactions
Citicoline + 1,2-diacylglycerol → Cytidine monophosphate + a phosphatidylcholinedetails
Citicoline + 1,2-Diacyl-sn-glycerol → Cytidine monophosphate + Phosphatidylcholinedetails
Citicoline + 1-Alkyl-2-acetyl-sn-glycerol → Cytidine monophosphate + 2-Acetyl-1-alkyl-sn-glycero-3-phosphocholinedetails
1-Alkyl-2-acylglycerol + Citicoline → 1-Radyl-2-acyl-sn-glycero-3-phosphocholine + Cytidine monophosphatedetails
General function:
Involved in phosphotransferase activity, for other substituted phosphate groups
Specific function:
Catalyzes both phosphatidylcholine and phosphatidylethanolamine biosynthesis from CDP-choline and CDP-ethanolamine, respectively. Involved in protein-dependent process of phospholipid transport to distribute phosphatidyl choline to the lumenal surface. Has a higher cholinephosphotransferase activity than ethanolaminephosphotransferase activity.
Gene Name:
CEPT1
Uniprot ID:
Q9Y6K0
Molecular weight:
46553.135
Reactions
Citicoline + 1,2-diacylglycerol → Cytidine monophosphate + a phosphatidylcholinedetails
Citicoline + 1,2-Diacyl-sn-glycerol → Cytidine monophosphate + Phosphatidylcholinedetails
Citicoline + 1-Alkyl-2-acetyl-sn-glycerol → Cytidine monophosphate + 2-Acetyl-1-alkyl-sn-glycero-3-phosphocholinedetails
1-Alkyl-2-acylglycerol + Citicoline → 1-Radyl-2-acyl-sn-glycero-3-phosphocholine + Cytidine monophosphatedetails
General function:
Not Available
Specific function:
Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose. May be involved in immune cell signaling as suggested by the second-messenger role of ADP-ribose, which activates TRPM2 as a mediator of oxidative/nitrosative stress (By similarity).
Gene Name:
ADPRM
Uniprot ID:
Q3LIE5
Molecular weight:
39529.105
Reactions
Citicoline + Water → Cytidine monophosphate + Phosphorylcholinedetails