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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-06-13 18:01:06 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. N5-(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
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
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
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified27.5 (10.0-45.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified38.0 (30.0-46.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified36.0 +/- 8.0 uMChildren (1-13 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified37.0 +/- 9.0 uMAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified35.0 +/- 10.0 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified38.0 (30.0-46.0) uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.8 +/- 1.0 uMAdult (>18 years old)MaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.8 +/- 1.8 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.62 (1.35-3.89) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified5.81+/- 1.23 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.5 +/- 0.5 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified1.08 (0.065-2.1) umol/mmol creatinineAdult (>18 years old)BothNormal
    details
    UrineDetected and Quantified0.19 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.00-74.25 umol/mmol creatinineAdult (>18 years old)BothNormal
      • David F. Putnam C...
    details
    UrineDetected and Quantified0.50 +/- 0.54 umol/mmol creatinineChildren (1-13 years old)MaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified1.1 +/- 0.84 umol/mmol creatinineAdult (>18 years old)MaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified0.99 +/- 0.69 umol/mmol creatinineAdult (>18 years old)FemaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified0.24 +/- 0.23 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.8 (0.2-1.7) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    BloodDetected and Quantified10.00 (5.00-15.00) uMChildren (1-13 years old)BothN-Acetylglutamate synthetase deficiency details
    BloodDetected and Quantified200.0 (100.0-300.0) uMChildren (1-13 years old)BothArgininosuccinic aciduria (ASL) details
    BloodDetected and Quantified13.0 (6.0-20.0) uMAdult (>18 years old)BothPermanent intestinal failure details
    BloodDetected and Quantified25.4 (23.4-27.4) uMAdult (>18 years old)BothAcute seizures details
    BloodDetected and Quantified26.8 (25.4-28.2) uMAdult (>18 years old)Both
    Epilepsy
    details
    BloodDetected and Quantified26.9 (25.2-28.6) uMChildren (1-13 years old)Both
    Epilepsy
    details
    BloodDetected and Quantified94.97 +/- 11.18 uMElderly (>65 years old)BothAlzheimer's disease details
    Cerebrospinal Fluid (CSF)Detected and Quantified27.0 +/- 2.6 uMAdult (>18 years old)BothAlzheimer's disease details
    Cerebrospinal Fluid (CSF)Detected and Quantified5.38 +/- 0.94 uMAdult (>18 years old)BothSchizophrenia details
    UrineDetected and Quantified21.0 +/- 2.8 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
    Associated Disorders and Diseases
    Disease References
    Alzheimer's disease
    1. 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
    1. MetaGene
    Epilepsy
    1. 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
    1. 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
    1. 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
    1. MetaGene
    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

    General function:
    Involved in argininosuccinate synthase activity
    Specific function:
    Not Available
    Gene Name:
    ASS1
    Uniprot ID:
    P00966
    Molecular weight:
    46530.055
    Reactions
    Adenosine triphosphate + Citrulline + L-Aspartic acid → Adenosine monophosphate + Pyrophosphate + Argininosuccinic aciddetails
    Adenosine triphosphate + Citrulline + L-Aspartic acid → Adenosine monophosphate + Pyrophosphate + Argininosuccinic aciddetails
    References
    1. Braissant O, Honegger P, Loup M, Iwase K, Takiguchi M, Bachmann C: Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain. Neurosci Lett. 1999 May 7;266(2):89-92. Pubmed: 10353334
    2. Braissant O, Gotoh T, Loup M, Mori M, Bachmann C: L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res. 1999 Jul 5;70(2):231-41. Pubmed: 10407171
    3. Keilhoff G, Reiser M, Stanarius A, Aoki E, Wolf G: Citrulline immunohistochemistry for demonstration of NOS activity in vivo and in vitro. Nitric Oxide. 2000 Aug;4(4):343-53. Pubmed: 10944418
    4. Zhang B, Cao GL, Domachowske J, Jackson MJ, Porasuphatana S, Rosen GM: Stable expression of varied levels of inducible nitric oxide synthase in primary cultures of endothelial cells. Anal Biochem. 2000 Nov 15;286(2):198-205. Pubmed: 11067741
    5. Zhang WY, Gotoh T, Oyadomari S, Mori M: Coinduction of inducible nitric oxide synthase and arginine recycling enzymes in cytokine-stimulated PC12 cells and high output production of nitric oxide. Brain Res Mol Brain Res. 2000 Nov 10;83(1-2):1-8. Pubmed: 11072090
    General function:
    Involved in protein-arginine deiminase activity
    Specific function:
    Catalyzes the deimination of arginine residues of proteins. May be involved in cytoskeletal reorganization in the egg and early embryo (By similarity).
    Gene Name:
    PADI6
    Uniprot ID:
    Q6TGC4
    Molecular weight:
    77726.735
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in protein-arginine deiminase activity
    Specific function:
    Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.
    Gene Name:
    PADI4
    Uniprot ID:
    Q9UM07
    Molecular weight:
    74078.65
    References
    1. Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA: Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2. Pubmed: 15345777
    2. Wysocka J, Allis CD, Coonrod S: Histone arginine methylation and its dynamic regulation. Front Biosci. 2006 Jan 1;11:344-55. Pubmed: 16146736
    3. Yamamoto K, Yamada R: Genome-wide single nucleotide polymorphism analyses of rheumatoid arthritis. J Autoimmun. 2005;25 Suppl:12-5. Epub 2005 Nov 2. Pubmed: 16271291
    4. Chang X, Han J: Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. Mol Carcinog. 2006 Mar;45(3):183-96. Pubmed: 16355400
    5. Okazaki Y, Suzuki A, Sawada T, Ohtake-Yamanaka M, Inoue T, Hasebe T, Yamada R, Yamamoto K: Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel autoantigen in rheumatoid arthritis. Biochem Biophys Res Commun. 2006 Mar 3;341(1):94-100. Epub 2006 Jan 6. Pubmed: 16412378
    General function:
    Involved in protein-arginine deiminase activity
    Specific function:
    Catalyzes the deimination of arginine residues of proteins.
    Gene Name:
    PADI3
    Uniprot ID:
    Q9ULW8
    Molecular weight:
    74742.705
    References
    1. Dong S, Kanno T, Yamaki A, Kojima T, Shiraiwa M, Kawada A, Mechin MC, Chavanas S, Serre G, Simon M, Takahara H: NF-Y and Sp1/Sp3 are involved in the transcriptional regulation of the peptidylarginine deiminase type III gene (PADI3) in human keratinocytes. Biochem J. 2006 Aug 1;397(3):449-59. Pubmed: 16671893
    2. Iida A, Nakamura Y: Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine deiminase types 1 and 3 loci on chromosomal band 1p36.13. J Hum Genet. 2004;49(7):387-90. Epub 2004 May 19. Pubmed: 15150696
    3. Kanno T, Kawada A, Yamanouchi J, Yosida-Noro C, Yoshiki A, Shiraiwa M, Kusakabe M, Manabe M, Tezuka T, Takahara H: Human peptidylarginine deiminase type III: molecular cloning and nucleotide sequence of the cDNA, properties of the recombinant enzyme, and immunohistochemical localization in human skin. J Invest Dermatol. 2000 Nov;115(5):813-23. Pubmed: 11069618
    General function:
    Involved in protein-arginine deiminase activity
    Specific function:
    Catalyzes the deimination of arginine residues of proteins (By similarity).
    Gene Name:
    PADI2
    Uniprot ID:
    Q9Y2J8
    Molecular weight:
    75563.35
    References
    1. Dong S, Kojima T, Shiraiwa M, Mechin MC, Chavanas S, Serre G, Simon M, Kawada A, Takahara H: Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors. J Invest Dermatol. 2005 May;124(5):1026-33. Pubmed: 15854045
    General function:
    Involved in protein-arginine deiminase activity
    Specific function:
    Catalyzes the deimination of arginine residues of proteins (By similarity).
    Gene Name:
    PADI1
    Uniprot ID:
    Q9ULC6
    Molecular weight:
    74664.97
    References
    1. Iida A, Nakamura Y: Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine deiminase types 1 and 3 loci on chromosomal band 1p36.13. J Hum Genet. 2004;49(7):387-90. Epub 2004 May 19. Pubmed: 15150696
    General function:
    Involved in hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
    Specific function:
    Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
    Gene Name:
    DDAH1
    Uniprot ID:
    O94760
    Molecular weight:
    20189.135
    Reactions
    Asymmetric dimethylarginine + Water → Dimethylamine + Citrullinedetails
    References
    1. Mishima T, Hamada T, Ui-Tei K, Takahashi F, Miyata Y, Imaki J, Suzuki H, Yamashita K: Expression of DDAH1 in chick and rat embryos. Brain Res Dev Brain Res. 2004 Feb 20;148(2):223-32. Pubmed: 14766200
    2. Tran CT, Fox MF, Vallance P, Leiper JM: Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics. 2000 Aug 15;68(1):101-5. Pubmed: 10950934
    3. Arrigoni FI, Vallance P, Haworth SG, Leiper JM: Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation. 2003 Mar 4;107(8):1195-201. Pubmed: 12615801
    General function:
    Involved in hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
    Specific function:
    Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
    Gene Name:
    DDAH2
    Uniprot ID:
    O95865
    Molecular weight:
    29643.54
    Reactions
    Asymmetric dimethylarginine + Water → Dimethylamine + Citrullinedetails
    References
    1. Tran CT, Fox MF, Vallance P, Leiper JM: Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics. 2000 Aug 15;68(1):101-5. Pubmed: 10950934
    2. Tain YL, Baylis C: Determination of dimethylarginine dimethylaminohydrolase activity in the kidney. Kidney Int. 2007 Oct;72(7):886-9. Epub 2007 Jul 25. Pubmed: 17653133
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.
    Gene Name:
    NOS2
    Uniprot ID:
    P35228
    Molecular weight:
    131116.3
    Reactions
    L-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Waterdetails
    NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
    L-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Waterdetails
    References
    1. Cunningham JM, Rayne RC: Radiochemical measurement of NOS activity by conversion of [14C]L-arginine to citrulline using HPLC separation. Methods Mol Biol. 1998;100:75-81. Pubmed: 10906995
    2. Keilhoff G, Reiser M, Stanarius A, Aoki E, Wolf G: Citrulline immunohistochemistry for demonstration of NOS activity in vivo and in vitro. Nitric Oxide. 2000 Aug;4(4):343-53. Pubmed: 10944418
    3. Conrad KP, Powers RW, Davis AK, Novak J: Citrulline is not the major product using the standard "NOS activity" assay on renal cortical homogenates. Am J Physiol Regul Integr Comp Physiol. 2002 Jan;282(1):R303-10. Pubmed: 11742852
    4. Knowles RG, Salter M: Measurement of NOS activity by conversion of radiolabeled arginine to citrulline using ion-exchange separation. Methods Mol Biol. 1998;100:67-73. Pubmed: 10906994
    5. Yi GB, McClendon D, Desaiah D, Goddard J, Lister A, Moffitt J, Meer RK, deShazo R, Lee KS, Rockhold RW: Fire ant venom alkaloid, isosolenopsin A, a potent and selective inhibitor of neuronal nitric oxide synthase. Int J Toxicol. 2003 Mar-Apr;22(2):81-6. Pubmed: 12745988
    General function:
    Involved in carboxyl- or carbamoyltransferase activity
    Specific function:
    Not Available
    Gene Name:
    OTC
    Uniprot ID:
    P00480
    Molecular weight:
    39934.775
    Reactions
    Carbamoyl phosphate + Ornithine → Phosphoric acid + Citrullinedetails
    References
    1. Quintero MJ, Muro-Pastor AM, Herrero A, Flores E: Arginine catabolism in the cyanobacterium Synechocystis sp. Strain PCC 6803 involves the urea cycle and arginase pathway. J Bacteriol. 2000 Feb;182(4):1008-15. Pubmed: 10648527
    2. Morizono H, Cabrera-Luque J, Shi D, Gallegos R, Yamaguchi S, Yu X, Allewell NM, Malamy MH, Tuchman M: Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis. J Bacteriol. 2006 Apr;188(8):2974-82. Pubmed: 16585758
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
    Gene Name:
    NOS1
    Uniprot ID:
    P29475
    Molecular weight:
    160969.095
    Reactions
    L-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Waterdetails
    NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
    L-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Waterdetails
    References
    1. Kominami S, Yamazaki T, Koga T, Hori H: EPR studies on the photo-induced intermediates of ferric NO complexes of rat neuronal nitric oxide synthase trapped at low temperature. J Biochem. 1999 Oct;126(4):756-61. Pubmed: 10502685
    2. Giraldi-Guimaraes A, Tenorio F, Bruning G, Mayer B, Mendez-Otero R, Cavalcante LA: Nitric oxide synthase expression in the opossum superior colliculus: a histochemical, immunohistochemical and biochemical study. Brain Behav Evol. 1999 Dec;54(6):303-13. Pubmed: 10681601
    3. Perry JM, Zhao Y, Marletta MA: Cu2+ and Zn2+ inhibit nitric-oxide synthase through an interaction with the reductase domain. J Biol Chem. 2000 May 12;275(19):14070-6. Pubmed: 10799481
    4. Adak S, Wang Q, Stuehr DJ: Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase. Implications for mechanism. J Biol Chem. 2000 Oct 27;275(43):33554-61. Pubmed: 10945985
    5. Yu W, Juang S, Lee J, Liu T, Cheng J: Decrease of neuronal nitric oxide synthase in the cerebellum of aged rats. Neurosci Lett. 2000 Sep 8;291(1):37-40. Pubmed: 10962148
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
    Gene Name:
    NOS3
    Uniprot ID:
    P29474
    Molecular weight:
    133273.59
    Reactions
    L-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Waterdetails
    NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
    L-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Waterdetails
    References
    1. Hayakawa H, Raij L: Relationship between hypercholesterolaemia, endothelial dysfunction and hypertension. J Hypertens. 1999 May;17(5):611-9. Pubmed: 10403604
    2. Trovati M, Massucco P, Mattiello L, Costamagna C, Aldieri E, Cavalot F, Anfossi G, Bosia A, Ghigo D: Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3':5'-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate concentrations. Diabetologia. 1999 Jul;42(7):831-9. Pubmed: 10440125
    3. McDuffie JE, Coaxum SD, Maleque MA: 5-hydroxytryptamine evokes endothelial nitric oxide synthase activation in bovine aortic endothelial cell cultures. Proc Soc Exp Biol Med. 1999 Sep;221(4):386-90. Pubmed: 10460702
    4. Tan E, Gurjar MV, Sharma RV, Bhalla RC: Estrogen receptor-alpha gene transfer into bovine aortic endothelial cells induces eNOS gene expression and inhibits cell migration. Cardiovasc Res. 1999 Aug 15;43(3):788-97. Pubmed: 10690351
    5. Abu-Soud HM, Ichimori K, Presta A, Stuehr DJ: Electron transfer, oxygen binding, and nitric oxide feedback inhibition in endothelial nitric-oxide synthase. J Biol Chem. 2000 Jun 9;275(23):17349-57. Pubmed: 10749853
    General function:
    Involved in argininosuccinate synthase activity
    Specific function:
    ATP + L-citrulline + L-aspartate = AMP + diphosphate + N(omega)-(L-arginino)succinate
    Gene Name:
    ASS1
    Uniprot ID:
    Q5T6L4
    Molecular weight:
    46530.1
    References
    1. Husson A, Brasse-Lagnel C, Fairand A, Renouf S, Lavoinne A: Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem. 2003 May;270(9):1887-99. Pubmed: 12709047
    2. Hammermann R, Bliesener N, Mossner J, Klasen S, Wiesinger H, Wessler I, Racke K: Inability of rat alveolar macrophages to recycle L-citrulline to L-arginine despite induction of argininosuccinate synthetase mRNA and protein, and inhibition of nitric oxide synthesis by exogenous L-citrulline. Naunyn Schmiedebergs Arch Pharmacol. 1998 Dec;358(6):601-7. Pubmed: 9879717
    3. Van Geldre LA, Timmermans JP, Lefebvre RA: L-citrulline recycling by argininosuccinate synthetase and lyase in rat gastric fundus. Eur J Pharmacol. 2002 Nov 29;455(2-3):149-60. Pubmed: 12445581
    4. Zandvliet MM, Rothuizen J: Transient hyperammonemia due to urea cycle enzyme deficiency in Irish wolfhounds. J Vet Intern Med. 2007 Mar-Apr;21(2):215-8. Pubmed: 17427379
    5. Takahashi H, Kagawa T, Kobayashi K, Hirabayashi H, Yui M, Begum L, Mine T, Takagi S, Saheki T, Shinohara Y: A case of adult-onset type II citrullinemia--deterioration of clinical course after infusion of hyperosmotic and high sugar solutions. Med Sci Monit. 2006 Feb;12(2):CS13-5. Epub 2006 Jan 26. Pubmed: 16449956
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Not Available
    Gene Name:
    NOS1
    Uniprot ID:
    B3VK56
    Molecular weight:
    160969.1