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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-09-18 19:24:11 UTC
HMDB IDHMDB0001413
Secondary Accession Numbers
  • HMDB01413
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
Data?1600457051
Synonyms
ValueSource
Cytidine 5'-(trihydrogen diphosphate), mono(2-(trimethylammonio)ethyl) esterChEBI
Cytidine 5'-(trihydrogen diphosphoric acid), mono(2-(trimethylammonio)ethyl) esterGenerator
CidifosMeSH
Diphosphate choline, cytidineMeSH
5'-Diphosphocholine, cytidineMeSH
Choline, cytidine diphosphateMeSH
CiticholineMeSH
Choline, CDPMeSH
CiticolineMeSH
CyticholineMeSH
Cytidine 5'-diphosphocholineMeSH
Cytidine diphosphate cholineMeSH
CDP CholineMeSH
Cytidine 5' diphosphocholineMeSH
CDP-cholineHMDB
Choline 5'-cytidine diphosphateHMDB
Choline 5’-cytidine diphosphateHMDB
Choline cytidine diphosphateHMDB
Cytidine 5'-(choline diphosphate)HMDB
Cytidine 5'-(cholinyl pyrophosphate)HMDB
Cytidine 5'-diphosphate cholineHMDB
Cytidine 5’-(choline diphosphate)HMDB
Cytidine 5’-(cholinyl pyrophosphate)HMDB
Cytidine 5’-diphosphate cholineHMDB
Cytidine 5’-diphosphocholineHMDB
Cytidine choline diphosphateHMDB
Cytidine diphosphate choline esterHMDB
Cytidine diphosphocholineHMDB
Cytidine diphosphorylcholineHMDB
Chemical FormulaC14H27N4O11P2
Average Molecular Weight489.3319
Monoisotopic Molecular Weight489.11515575
IUPAC Name{[(2R,3S,4R,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}({hydroxy[2-(trimethylazaniumyl)ethoxy]phosphoryl}oxy)phosphinic acid
Traditional Namecdp-choline(1+)
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)/p+1/t9-,11-,12-,13-/m1/s1
InChI KeyRZZPDXZPRHQOCG-OJAKKHQRSA-O
Chemical Taxonomy
Description belongs to the class of organic compounds known as pterins and derivatives. These are polycyclic aromatic compounds containing a pterin moiety, which consist of a pteridine ring bearing a ketone and an amine group to form 2-aminopteridin-4(3H)-one.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentPterins and derivatives
Alternative Parents
Substituents
  • Pterin
  • Aminobenzoic acid
  • Aminobenzoic acid or derivatives
  • Benzoic acid or derivatives
  • Benzoic acid
  • Benzoyl
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Hydroxypyrimidine
  • Secondary aliphatic/aromatic amine
  • Monocyclic benzene moiety
  • Pyrimidine
  • Benzenoid
  • Heteroaromatic compound
  • Amino acid or derivatives
  • Amino acid
  • Ketimine
  • Azacycle
  • Secondary amine
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Carboxylic acid
  • Organic nitrogen compound
  • Imine
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

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 g/LALOGPS
logP-1.1ALOGPS
logP-7.1ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)1.85ChemAxon
pKa (Strongest Basic)-0.032ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area210.67 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity114.71 m³·mol⁻¹ChemAxon
Polarizability42.67 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0006-0001900000-a9f38ff6b185b45f04b3Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-03e9-0590000000-b021677d064d65810ee0Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-0900000000-7570bbb10dd9fa288442Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-000i-0000900000-8b411373962b073b4d22Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positivesplash10-000i-0001900000-6e7cc437ad79eb13c032Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-01qi-1932200000-9c3803cefdd9c6285a7cSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-004i-6505900000-3d534aab6e40915c3642Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-004i-6505900000-fc13e5ad403e7faf8218Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-004i-6505900000-3d534aab6e40915c3642Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-004i-6505900000-fc13e5ad403e7faf8218Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0000900000-8b411373962b073b4d22Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0001900000-6e7cc437ad79eb13c032Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-01qi-1932200000-4a7ae92c6e127d2ce453Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-2910000000-16739ec448981ed6c806Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-4900000000-ebcd1f8663a2ad408f47Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9700000000-626eb1582def7bb92bdfSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen LocationsNot Available
Tissue Locations
  • Brain
  • Erythrocyte
  • Intestine
  • Placenta
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB12153
Phenol Explorer Compound IDNot Available
FooDB IDFDB022608
KNApSAcK IDC00007231
Chemspider ID13208
KEGG Compound IDC00307
BioCyc IDCDP-CHOLINE
BiGG IDNot Available
Wikipedia LinkCiticoline
METLIN ID6229
PubChem Compound13805
PDB IDNot Available
ChEBI ID49086
Food Biomarker OntologyNot Available
VMH IDCDPCHOL
MarkerDB ID
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:6574471 ]
  8. Hayashida K: [Usefulness of SPECT images in helping radiologists understand brain diseases]. Nihon Igaku Hoshasen Gakkai Zasshi. 2001 Apr;61(5):208-14. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:17171187 ]
  14. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

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