Record Information
Version 1.0
Update Date 1/22/2018 12:54:54 PM
Metabolite IDPAMDB000198
Identification
Name: Citrulline
Description:Citrulline is an amino acid made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family (NOS; EC 1.14.13.39). In this reaction arginine is first oxidized into N-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with the release of nitric oxide.; EC 1.14.13.39). Citrulline's name is derived from citrullus, the Latin word for watermelon, from which it was first isolated.
Structure
Thumb
Synonyms:
  • α-amino-γ-ureidovalerate
  • α-amino-γ-ureidovaleric acid
  • γureidonorvaline
  • (2S)-2-amino-5-(carbamoylamino)pentanoate
  • (2S)-2-amino-5-(carbamoylamino)pentanoic acid
  • (S)-2-amino-5-(aminocarbonyl)aminopentanoate
  • (S)-2-amino-5-(aminocarbonyl)aminopentanoic acid
  • (S)-2-Amino-5-ureidopentanoate
  • (S)-2-Amino-5-ureidopentanoic acid
  • 2-Amino-5-uredovalerate
  • 2-Amino-5-uredovaleric acid
  • 2-Amino-5-ureidovalerate
  • 2-Amino-5-ureidovaleric acid
  • A-Amino-D-ureidovalerate
  • A-Amino-D-ureidovaleric acid
  • a-amino-delta-Ureidovalerate
  • a-amino-delta-Ureidovaleric acid
  • a-amino-g-Ureidovalerate
  • a-amino-g-Ureidovaleric acid
  • a-amino-δ-Ureidovalerate
  • a-amino-δ-Ureidovaleric acid
  • Alpha-Amino-delta-ureidovalerate
  • Alpha-Amino-delta-ureidovaleric acid
  • Alpha-Amino-gamma-ureidovalerate
  • Alpha-Amino-gamma-ureidovaleric acid
  • Amino-ureidovalerate
  • Amino-ureidovaleric acid
  • CIR
  • CIT
  • Citrulline
  • Cytrulline
  • D-Ureidonorvaline
  • Delta-Ureidonorvaline
  • DL-citrulline
  • Gammaureidonorvaline
  • H-Cit-oh
  • L(+)-2-Amino-5-ureidovalerate
  • L(+)-2-Amino-5-ureidovaleric acid
  • L(+)-Citrulline
  • L-2-Amino-5-ureido-valerate
  • L-2-Amino-5-ureido-valeric acid
  • L-2-Amino-5-ureidovalerate
  • L-2-Amino-5-ureidovaleric acid
  • L-Citrulline
  • L-Cytrulline
  • L-N5-carbamoyl-Ornithine
  • Nγ-carbamylornithine
  • N()-Carbamylornithine
  • N(5)-(Aminocarbonyl)-DL-Ornithine
  • N(delta)-Carbamylornithine
  • N(δ)-Carbamylornithine
  • N-Carbamylornithine
  • N5-(Aminocarbonyl)-L-ornithine
  • N5-(aminocarbonyl)-Ornithine
  • N5-(Aminocarbonyl)ornithine
  • N5-Carbamoyl-L-ornithine
  • N5-carbamoylornithine
  • N5-carbamylornithine
  • Nγ-carbamylornithine
  • N5-(Aminocarbonyl)-L-ornithine
  • N5-(aminocarbonyl)ornithine
  • ND-carbamylornithine
  • Ndelta-carbamy-ornithine
  • Ndelta-carbamylornithine
  • Ngamma-carbamylornithine
  • Sitrulline
  • Ureidonorvaline
  • Ureidovalerate
  • Ureidovaleric acid
  • α-amino-γ-Ureidovalerate
  • α-amino-γ-Ureidovaleric acid
  • α-amino-δ-Ureidovalerate
  • α-amino-δ-Ureidovaleric acid
  • δ-Ureidonorvaline
Chemical Formula: C6H13N3O3
Average Molecular Weight: 175.1857
Monoisotopic Molecular Weight: 175.095691297
InChI Key: RHGKLRLOHDJJDR-BYPYZUCNSA-N
InChI:InChI=1S/C6H13N3O3/c7-4(5(10)11)2-1-3-9-6(8)12/h4H,1-3,7H2,(H,10,11)(H3,8,9,12)/t4-/m0/s1
CAS number: 372-75-8
IUPAC Name:(2S)-2-amino-5-(carbamoylamino)pentanoic acid
Traditional IUPAC Name: L-citrulline
SMILES:N[C@@H](CCCNC(N)=O)C(O)=O
Chemical Taxonomy
Taxonomy DescriptionThis compound belongs to the class of organic compounds known as d-alpha-amino acids. These are alpha amino acids which have the D-configuration of the alpha-carbon atom.
Kingdom Organic compounds
Super ClassOrganic acids and derivatives
Class Carboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct Parent D-alpha-amino acids
Alternative Parents
Substituents
  • D-alpha-amino acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • Isourea
  • Carboximidamide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboximidic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Imine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular Framework Aliphatic acyclic compounds
External Descriptors
Physical Properties
State: Solid
Charge:0
Melting point: 235.5 °C
Experimental Properties:
PropertyValueSource
Water Solubility:212 mg/mL [HMP experimental]PhysProp
LogP:-3.19 [SANGSTER (1994)]PhysProp
Predicted Properties
PropertyValueSource
Water Solubility21.8 mg/mLALOGPS
logP-3.3ALOGPS
logP-3.9ChemAxon
logS-0.9ALOGPS
pKa (Strongest Acidic)2.27ChemAxon
pKa (Strongest Basic)9.23ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area118.44 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity41.33 m3·mol-1ChemAxon
Polarizability17.35 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations: Cytoplasm
Reactions:
Pathways:
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0a4i-0920000000-2d92b63cd5d9648023b8View in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-00di-9610000000-2e7cd23afc2adcef35a3View in MoNA
GC-MSGC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4i-0900000000-4c1d7af748a47e489949View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00di-9000000000-988fced362fc0da157c9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00di-9000000000-0818e0e8bcee12692498View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004j-0900000000-5fa8a338dcd2f2a6bdd2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-16763200aa07f7629ad4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-03di-3900000000-d9cfc5187aa799f6f978View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-10ee9a593e13550bec1cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-45d272576af34c9512a3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-3900000000-6177a284fdea5a3f1306View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-d9456d45e2dbd7a3df10View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-ada57cdc73bda93be483View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-008a-0904000000-23fbe48f82e515087d68View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-03di-5900000000-78afcbaf8b8b3eabf174View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-001i-0900000000-8fb191d4c20fd54b9282View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-00di-0900000000-da484f0362a8dca5127eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-00e9-0900000000-46229b4f77feabb3f857View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-001i-0900000000-4aca1022c393602a297dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-001i-0900000000-3bc2eff2e907b7734cc8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-001i-3900000000-2613bf40e3be814da86fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0006-9300000000-e83287bbc060eb9cf6f3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-056r-0900000000-694a8872bdfd7eec1f2bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-08fr-2900000000-15b4711991ea9985fb2bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00di-9300000000-915fbb73e0b728420e4aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-00di-9000000000-67e60567f5c062728350View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-00di-9000000000-25140713431edd7c5eeaView in MoNA
1D NMR13C NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,1H] 2D NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
References:
  • Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. Pubmed: 19561621
  • Booth FA, Haworth JC, Dilling LA, Perry TL, Greenberg CR, Seargeant LE, Penn AM, Rhead WJ: Mitochondrial encephalomyopathy with associated aminoacidopathy in a male sibship. J Pediatr. 1989 Jul;115(1):81-8. Pubmed: 2738799
  • Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B: Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000 Dec;119(6):1496-505. Pubmed: 11113071
  • Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. Pubmed: 12297216
  • DeLong GR, Glick TH: Ammonia metabolism in Reye syndrome and the effect of citrulline. Ann Neurol. 1982 Jan;11(1):53-8. Pubmed: 7059128
  • Engelborghs S, Marescau B, De Deyn PP: Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochem Res. 2003 Aug;28(8):1145-50. Pubmed: 12834252
  • Facchinetti F, Longo M, Piccinini F, Neri I, Volpe A: L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release. J Soc Gynecol Investig. 1999 Jul-Aug;6(4):202-7. Pubmed: 10486782
  • Fleisher LD, Harris CJ, Mitchell DA, Nadler HL: Citrullinemia: prenatal diagnosis of an affected fetus. Am J Hum Genet. 1983 Jan;35(1):85-90. Pubmed: 6823975
  • Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA: Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem. 1984 Mar;42(3):833-7. Pubmed: 6198473
  • Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. Pubmed: 17379776
  • Jianfeng G, Weiming Z, Ning L, Fangnan L, Li T, Nan L, Jieshou L: Serum citrulline is a simple quantitative marker for small intestinal enterocytes mass and absorption function in short bowel patients. J Surg Res. 2005 Aug;127(2):177-82. Pubmed: 15921697
  • Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
  • Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
  • Le Boucher J, Charret C, Coudray-Lucas C, Giboudeau J, Cynober L: Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A. Clin Chem. 1997 Aug;43(8 Pt 1):1421-8. Pubmed: 9267323
  • Liappis N, Pohl B, Weber HP, el-Karkani H: [Free amino acids in the saliva of children with phenylketonuria] Klin Padiatr. 1986 Jan-Feb;198(1):25-8. Pubmed: 3959486
  • Maruyama H, Ogawa M, Nishio T, Kobayashi K, Saheki T, Sunohara N: Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels. J Neurol Sci. 2001 Jan 1;182(2):167-70. Pubmed: 11137523
  • McLaurin J, Moscarello MA: The preparation of antibodies reactive against citrulline-containing charge isomers of myelin basic protein but not against the arginine-containing charge isomers. Anal Biochem. 1990 Dec;191(2):272-7. Pubmed: 1707596
  • Melis GC, Boelens PG, van der Sijp JR, Popovici T, De Bandt JP, Cynober L, van Leeuwen PA: The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients. Br J Nutr. 2005 Jul;94(1):19-26. Pubmed: 16115328
  • Origuchi Y, Ushijima T, Sakaguchi M, Akaboshi I, Matsuda I: Citrullinemia presenting as uncontrollable epilepsy. Brain Dev. 1984;6(3):328-31. Pubmed: 6486381
  • Potter MA, Zeesman S, Brennan B, Kobayashi K, Gao HZ, Tabata A, Saheki T, Whelan DT: Pregnancy in a healthy woman with untreated citrullinemia. Am J Med Genet A. 2004 Aug 15;129(1):77-82. Pubmed: 15266621
  • Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24. Pubmed: 14992292
  • Reparon-Schuijt CC, van Esch WJ, van Kooten C, Schellekens GA, de Jong BA, van Venrooij WJ, Breedveld FC, Verweij CL: Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis. Arthritis Rheum. 2001 Jan;44(1):41-7. Pubmed: 11212174
  • Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  • van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. Pubmed: 17765195
  • Wheatley DN, Kilfeather R, Stitt A, Campbell E: Integrity and stability of the citrulline-arginine pathway in normal and tumour cell lines. Cancer Lett. 2005 Sep 28;227(2):141-52. Pubmed: 16112417
  • Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
Synthesis Reference: Kakimoto, Toshio; Shibatani, Takeji; Nishimura, Noriyuki; Chibata, Ichiro. Enzymic production of L-citrulline by Pseudomonas putida. Applied Microbiology (1971), 22(6), 992-9.
Material Safety Data Sheet (MSDS) Download (PDF)
External Links:
ResourceLink
CHEBI ID18211
HMDB IDHMDB00904
Pubchem Compound ID9750
Kegg IDC00327
ChemSpider ID9367
WikipediaCitrulline
BioCyc IDL-CITRULLINE
EcoCyc IDL-CITRULLINE
Ligand ExpoCIR