Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:09:33 UTC
HMDB IDHMDB00904
Secondary Accession NumbersNone
Metabolite Identification
Common NameCitrulline
DescriptionCitrulline 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
  1. (2S)-2-amino-5-(carbamoylamino)pentanoate
  2. (2S)-2-amino-5-(carbamoylamino)pentanoic acid
  3. (S)-2-amino-5-(aminocarbonyl)aminopentanoate
  4. (S)-2-amino-5-(aminocarbonyl)aminopentanoic acid
  5. (S)-2-Amino-5-ureidopentanoate
  6. (S)-2-Amino-5-ureidopentanoic acid
  7. 2-Amino-5-uredovalerate
  8. 2-Amino-5-uredovaleric acid
  9. 2-Amino-5-ureidovalerate
  10. 2-Amino-5-ureidovaleric acid
  11. A-Amino-D-ureidovalerate
  12. A-Amino-D-ureidovaleric acid
  13. alpha-Amino-delta-ureidovalerate
  14. alpha-Amino-delta-ureidovaleric acid
  15. alpha-Amino-gamma-ureidovalerate
  16. alpha-Amino-gamma-ureidovaleric acid
  17. Amino-ureidovalerate
  18. Amino-ureidovaleric acid
  19. CIR
  20. CIT
  21. Cytrulline
  22. D-Ureidonorvaline
  23. delta-Ureidonorvaline
  24. DL-citrulline
  25. Gammaureidonorvaline
  26. H-Cit-oh
  27. L(+)-2-Amino-5-ureidovalerate
  28. L(+)-2-Amino-5-ureidovaleric acid
  29. L(+)-Citrulline
  30. L-2-Amino-5-ureido-valerate
  31. L-2-Amino-5-ureido-valeric acid
  32. L-2-Amino-5-ureidovalerate
  33. L-2-Amino-5-ureidovaleric acid
  34. L-Citrulline
  35. L-Cytrulline
  36. L-N5-carbamoyl-Ornithine
  37. N()-Carbamylornithine
  38. N(5)-(Aminocarbonyl)-DL-Ornithine
  39. N(delta)-Carbamylornithine
  40. N-Carbamylornithine
  41. N5-(Aminocarbonyl)-L-ornithine
  42. N5-(aminocarbonyl)-Ornithine
  43. N5-(Aminocarbonyl)ornithine
  44. N5-Carbamoyl-L-ornithine
  45. N5-carbamoylornithine
  46. N5-carbamylornithine
  47. N<SUP>5</SUP>-(aminocarbonyl)ornithine
  48. ND-carbamylornithine
  49. Ndelta-carbamy-ornithine
  50. Ndelta-carbamylornithine
  51. Ngamma-carbamylornithine
  52. Sitrulline
  53. Ureidonorvaline
  54. Ureidovalerate
  55. Ureidovaleric acid
Chemical FormulaC6H13N3O3
Average Molecular Weight175.1857
Monoisotopic Molecular Weight175.095691297
IUPAC Name(2S)-2-amino-5-(carbamoylamino)pentanoic acid
Traditional IUPAC NameL-citrulline
CAS Registry Number372-75-8
SMILES
N[C@@H](CCCNC(N)=O)C(O)=O
InChI Identifier
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
InChI KeyRHGKLRLOHDJJDR-BYPYZUCNSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aliphatic Acyclic Compounds
  • citrullines(ChEBI)
Substituents
  • Carboxylic Acid
  • Polyamine
  • Primary Aliphatic Amine (Alkylamine)
  • Urea
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Alanine and aspartate metabolism
  • Component of Arginine and proline metabolism
ApplicationNot Available
Cellular locations
  • Mitochondria
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point235.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility212 mg/mLNot Available
LogP-3.19SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility21.8 g/LALOGPS
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 area118.44ChemAxon
rotatable bond count5ChemAxon
refractivity41.33ChemAxon
polarizability17.35ChemAxon
Spectra
Spectra
Biological Properties
Cellular Locations
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Bladder
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Myelin
  • Nerve Cells
  • Neuron
  • Placenta
  • Platelet
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Aspartate MetabolismSMP00067map00250
Urea CycleSMP00059map00330
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified27.5 (10.0-45.0) uMAdult (>18 years old)BothNormal
BloodDetected and Quantified38.0 (30.0-46.0) uMAdult (>18 years old)BothNormal
BloodDetected and Quantified36.0 +/- 8.0 uMChildren (1-13 year old)MaleNormal
  • Geigy Scient...
BloodDetected and Quantified37.0 +/- 9.0 uMAdult (>18 years old)MaleNormal
  • Geigy Scient...
BloodDetected and Quantified35.0 +/- 10.0 uMAdult (>18 years old)FemaleNormal
  • Geigy Scient...
BloodDetected and Quantified38.0 (30.0-46.0) uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified2.8 +/- 1.0 uMAdult (>18 years old)MaleNormal
Cerebrospinal Fluid (CSF)Detected and Quantified2.8 +/- 1.8 uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified2.62 (1.35-3.89) uMAdult (>18 years old)BothNormal
Cerebrospinal Fluid (CSF)Detected and Quantified5.81+/- 1.23 uMAdult (>18 years old)BothNormal
Cerebrospinal Fluid (CSF)Detected and Quantified1.5 +/- 0.5 uMAdult (>18 years old)BothNormal
  • Geigy Scient...
UrineDetected and Quantified1.08 (0.065-2.1) umol/mmol creatinineAdult (>18 years old)BothNormal
    UrineDetected and Quantified0.19 umol/mmol creatinineAdult (>18 years old)BothNormal
    UrineDetected and Quantified0.00-74.25 umol/mmol creatinineAdult (>18 years old)BothNormal
    • David F. Put...
    UrineDetected and Quantified0.50 +/- 0.54 umol/mmol creatinineChildren (1-13 year old)MaleNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified1.1 +/- 0.84 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified0.99 +/- 0.69 umol/mmol creatinineAdult (>18 years old)FemaleNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified0.24 +/- 0.23 umol/mmol creatinineAdult (>18 years old)BothNormal
    UrineDetected and Quantified0.8 (0.2-1.7) umol/mmol creatinineAdult (>18 years old)BothCommentNormal
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReference
    BloodDetected and Quantified10.00 (5.00-15.00) uMChildren (1-13 year old)BothN-Acetylglutamate synthetase deficiency
    BloodDetected and Quantified200.0 (100.0-300.0) uMChildren (1-13 year old)BothArgininosuccinic aciduria (ASL)
    BloodDetected and Quantified13.0 (6.0-20.0) uMAdult (>18 years old)BothPermanent intestinal failure
    BloodDetected and Quantified25.4 (23.4-27.4) uMAdult (>18 years old)BothCommentSeizures
    BloodDetected and Quantified26.8 (25.4-28.2) uMAdult (>18 years old)BothCommentEpilepsy
    BloodDetected and Quantified26.9 (25.2-28.6) uMChildren (1-13 year old)BothCommentEpilepsy
    BloodDetected and Quantified94.97 +/- 11.18 uMElderly (>65 years old)BothAlzheimer's disease
    Cerebrospinal Fluid (CSF)Detected and Quantified27.0 +/- 2.6 uMAdult (>18 years old)BothAlzheimer's disease
    Cerebrospinal Fluid (CSF)Detected and Quantified5.38 +/- 0.94 uMAdult (>18 years old)BothSchizophrenia
    UrineDetected and Quantified21.0 +/- 2.8 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease
    Associated Disorders and Diseases
    Disease References
    Alzheimer's disease
    • Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. Pubmed: 17031479
    Argininosuccinic aciduria
    Epilepsy
    • 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
    Schizophrenia
    • Do KQ, Lauer CJ, Schreiber W, Zollinger M, Gutteck-Amsler U, Cuenod M, Holsboer F: gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. J Neurochem. 1995 Dec;65(6):2652-62. Pubmed: 7595563
    Intestinal failure
    • 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
    N-acetylglutamate synthetase deficiency
    Associated OMIM IDs
    DrugBank IDDB00155
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB011841
    KNApSAcK IDC00001348
    Chemspider ID9367
    KEGG Compound IDC00327
    BioCyc IDL-CITRULLINE
    BiGG ID34627
    Wikipedia LinkCitrulline
    NuGOwiki LinkHMDB00904
    Metagene LinkHMDB00904
    METLIN ID16
    PubChem Compound9750
    PDB IDCIR
    ChEBI ID16349
    References
    Synthesis ReferenceKakimoto, 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)
    General References
    1. 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
    2. 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
    3. 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
    4. 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
    5. 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
    6. 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
    7. 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
    8. 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
    9. DeLong GR, Glick TH: Ammonia metabolism in Reye syndrome and the effect of citrulline. Ann Neurol. 1982 Jan;11(1):53-8. Pubmed: 7059128
    10. 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
    11. 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
    12. 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
    13. 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
    14. 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
    15. 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
    16. 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
    17. 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
    18. 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
    19. Origuchi Y, Ushijima T, Sakaguchi M, Akaboshi I, Matsuda I: Citrullinemia presenting as uncontrollable epilepsy. Brain Dev. 1984;6(3):328-31. Pubmed: 6486381
    20. 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

    Enzymes

    Gene Name:
    ASS1
    Uniprot ID:
    P00966
    Reactions
    Adenosine triphosphate + Citrulline + L-Aspartic acid unknown Adenosine monophosphate + Pyrophosphate + Argininosuccinic aciddetails
    Adenosine triphosphate + Citrulline + L-Aspartic acid unknown Adenosine monophosphate + Pyrophosphate + Argininosuccinic aciddetails
    Gene Name:
    PADI6
    Uniprot ID:
    Q6TGC4
    Gene Name:
    PADI4
    Uniprot ID:
    Q9UM07
    Gene Name:
    PADI3
    Uniprot ID:
    Q9ULW8
    Gene Name:
    PADI2
    Uniprot ID:
    Q9Y2J8
    Gene Name:
    PADI1
    Uniprot ID:
    Q9ULC6
    Gene Name:
    DDAH1
    Uniprot ID:
    O94760
    Reactions
    Asymmetric dimethylarginine + Water unknown Dimethylamine + Citrullinedetails
    Gene Name:
    DDAH2
    Uniprot ID:
    O95865
    Reactions
    Asymmetric dimethylarginine + Water unknown Dimethylamine + Citrullinedetails
    Gene Name:
    NOS2
    Uniprot ID:
    P35228
    Reactions
    L-Arginine + NADPH + Oxygen unknown Citrulline + Nitric oxide + NADP + Waterdetails
    NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion unknown NADP + Nitric oxide + Citrulline + Waterdetails
    L-Arginine + Oxygen + NADPH + Hydrogen Ion unknown Nitric oxide + Citrulline + NADP + Waterdetails
    Gene Name:
    OTC
    Uniprot ID:
    P00480
    Reactions
    Carbamoyl phosphate + Ornithine unknown Phosphoric acid + Citrullinedetails
    Gene Name:
    NOS1
    Uniprot ID:
    P29475
    Reactions
    L-Arginine + NADPH + Oxygen unknown Citrulline + Nitric oxide + NADP + Waterdetails
    NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion unknown NADP + Nitric oxide + Citrulline + Waterdetails
    L-Arginine + Oxygen + NADPH + Hydrogen Ion unknown Nitric oxide + Citrulline + NADP + Waterdetails
    Gene Name:
    NOS3
    Uniprot ID:
    P29474
    Reactions
    L-Arginine + NADPH + Oxygen unknown Citrulline + Nitric oxide + NADP + Waterdetails
    NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion unknown NADP + Nitric oxide + Citrulline + Waterdetails
    L-Arginine + Oxygen + NADPH + Hydrogen Ion unknown Nitric oxide + Citrulline + NADP + Waterdetails
    Gene Name:
    ASS1
    Uniprot ID:
    Q5T6L4
    Gene Name:
    NOS1
    Uniprot ID:
    B3VK56