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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-06-11 23:20:21 UTC
HMDB IDHMDB00214
Secondary Accession Numbers
  • HMDB00818
  • HMDB04984
Metabolite Identification
Common NameOrnithine
DescriptionOrnithine is an amino acid produced in the urea cycle by the splitting off of urea from arginine. It is a central part of the urea cycle, which allows for the disposal of excess nitrogen. L-Ornithine is also a precursor of citrulline and arginine. In order for ornithine produced in the cytosol to be converted to citrulline, it must first cross the inner mitochondrial membrane into the mitochondrial matrix where it is carbamylated by ornithine transcarbamylase. This transfer is mediated by the mitochondrial ornithine transporter (SLC25A15; AF112968; ORNT1). Mutations in the mitochondrial ornithine transporter result in hyperammonemia, hyperornithinemia, homocitrullinuria (HHH) syndrome, a disorder of the urea cycle. (PMID 16256388 ) The pathophysiology of the disease may involve diminished ornithine transport into mitochondria, resulting in ornithine accumulation in the cytoplasm and reduced ability to clear carbamoyl phosphate and ammonia loads. (OMIM 838970 ).
Structure
Thumb
Synonyms
  1. (+)-S-Ornithine
  2. (S)-2,5-Diaminopentanoate
  3. (S)-2,5-Diaminopentanoic acid
  4. (S)-a,D-Diaminovalerate
  5. (S)-a,D-Diaminovaleric acid
  6. (S)-Ornithine
  7. 5-Amino-L-Norvaline
  8. L-(-)-Ornithine
  9. L-Ornithine
Chemical FormulaC5H12N2O2
Average Molecular Weight132.161
Monoisotopic Molecular Weight132.089877638
IUPAC Name(2S)-2,5-diaminopentanoic acid
Traditional IUPAC NameL-ornithine
CAS Registry Number70-26-8
SMILES
NCCC[C@H](N)C(O)=O
InChI Identifier
InChI=1S/C5H12N2O2/c6-3-1-2-4(7)5(8)9/h4H,1-3,6-7H2,(H,8,9)/t4-/m0/s1
InChI KeyAHLPHDHHMVZTML-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
  • alpha-amino acid(ChEBI)
Substituents
  • Carboxylic Acid
  • Polyamine
  • Primary Aliphatic Amine (Alkylamine)
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Arginine and proline metabolism
  • Component of Glycine, serine and threonine metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
  • Mitochondria
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point140 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility620 mg/mLNot Available
LogP-4.22SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility172 g/LALOGPS
logP-3.6ALOGPS
logP-3.7ChemAxon
logS0.11ALOGPS
pKa (strongest acidic)2.67ChemAxon
pKa (strongest basic)10.29ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count3ChemAxon
polar surface area89.34ChemAxon
rotatable bond count4ChemAxon
refractivity33.21ChemAxon
polarizability13.94ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Gut
  • Liver
  • Prostate
  • Skin
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Glycine and Serine MetabolismSMP00004map00260
Spermidine and Spermine BiosynthesisSMP00445Not Available
Urea CycleSMP00059map00330
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified55.0 (39.0-71.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified93.8 +/- 41.3 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified90.0 +/- 20.0 uMNewborn (0-30 days old)Not SpecifiedNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified47.0 +/- 14.0 uMChildren (1-13 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified65.0 +/- 18.0 uMAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified54.0 +/- 18.0 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified109.0 +/- 32.0 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified34.3 +/- 13.0 uMChildren (1-13 years old)BothNormal details
BloodDetected and Quantified66.9 +/- 15.3 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified4.87 (3.48-6.26) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified8.3 +/- 4.7 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified6.0 +/- 1.5 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified4.9 +/- 1.6 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified3.7 +/- 1.0 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified4.5 +/- 2.2 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified>10 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified5.3 (2.0-8.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.98 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified5.0 (2.0-8.0) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified2.19 +/- 3.21 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified2.0 (0.90-2.94) umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.0024 - 0.0111 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.987 (0.132-1.842) umol/mmol creatinineAdult (>18 years old)BothNormal
    details
    UrineDetected and Quantified4.11 +/- 1.37 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified4.4 (1.2-22.1) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0.050 (0.0-0.098) umol/mmol creatinineNewborn (0-30 days old)BothNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified0.78 +/- 0.36 umol/mmol creatinineChildren (1-13 years old)MaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified3.1 +/- 1.46 umol/mmol creatinineAdult (>18 years old)MaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified2.6 +/- 1.30 umol/mmol creatinineAdult (>18 years old)FemaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified0.9 umol/mmol creatinineAdult (>18 years old)BothNormal details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    BloodDetected and Quantified65.4 +/- 30.4 uMAdult (>18 years old)Not SpecifiedHeart Transplant details
    BloodDetected and Quantified41.0 +/- 16.0 uMAdult (>18 years old)BothOrnithine transcarbamylase (OTC) deficiency details
    BloodDetected and Quantified37.8 +/- 12.0 uMChildren (1-13 years old)BothUremia details
    BloodDetected and Quantified68.35 +/- 22.43 uMAdult (>18 years old)BothAlzheimer's disease details
    Cerebrospinal Fluid (CSF)Detected and Quantified7.6 +/- 3.1 uMChildren (1-13 years old)Not SpecifiedLeukemia details
    Cerebrospinal Fluid (CSF)Detected and Quantified6.9 +/- 3.6 uMChildren (1-13 years old)Not Specified
    Leukemia
    details
    UrineDetected and Quantified350.0 (200.0-500.0) umol/mmol creatinineChildren (1-13 years old)BothCystinuria details
    UrineDetected and Quantified12.34 +/- 5.07 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
    UrineDetected and Quantified1285.00 (70.00-2500.00) umol/mmol creatinineChildren (1-13 years old)BothHyperdibasic aminoaciduria I details
    UrineDetected and Quantified60.00 (20.00-100.00) umol/mmol creatinineChildren (1-13 years old)BothLysinuric protein intolerance 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
    Cystinuria
    1. MetaGene
    Leukemia
    1. Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. Pubmed: 15911239
    Lysinuric protein intolerance
    1. MetaGene
    Ornithine transcarbamylase deficiency
    1. Harada E, Nishiyori A, Tokunaga Y, Watanabe Y, Kuriya N, Kumashiro R, Kuno T, Kuromaru R, Hirose S, Ichikawa K, Yoshino M: Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile. Pediatr Int. 2006 Apr;48(2):105-11. Pubmed: 16635166
    Uremia
    1. Canepa A, Filho JC, Gutierrez A, Carrea A, Forsberg AM, Nilsson E, Verrina E, Perfumo F, Bergstrom J: Free amino acids in plasma, red blood cells, polymorphonuclear leukocytes, and muscle in normal and uraemic children. Nephrol Dial Transplant. 2002 Mar;17(3):413-21. Pubmed: 11865086
    Hyperdibasic aminoaciduria I
    1. MetaGene
    Associated OMIM IDs
    DrugBank IDDB00129
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB003654
    KNApSAcK IDNot Available
    Chemspider ID6026
    KEGG Compound IDC00077
    BioCyc IDL-ORNITHINE
    BiGG ID37976
    Wikipedia LinkOrnithine
    NuGOwiki LinkHMDB00214
    Metagene LinkHMDB00214
    METLIN ID27
    PubChem Compound6262
    PDB IDORN
    ChEBI ID15729
    References
    Synthesis ReferenceZhang, Peng; Zhang, Shurong; Liu, Chunqiao; Yang, Yuhong. Method for preparing L-ornithine by enzymatic conversion. Faming Zhuanli Shenqing Gongkai Shuomingshu (2007), 8pp.
    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. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. Pubmed: 12097436
    3. Nicholson JK, O'Flynn MP, Sadler PJ, Macleod AF, Juul SM, Sonksen PH: Proton-nuclear-magnetic-resonance studies of serum, plasma and urine from fasting normal and diabetic subjects. Biochem J. 1984 Jan 15;217(2):365-75. Pubmed: 6696735
    4. 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
    5. 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
    6. Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. Pubmed: 15911239
    7. 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
    8. Peters T, Thaete C, Wolf S, Popp A, Sedlmeier R, Grosse J, Nehls MC, Russ A, Schlueter V: A mouse model for cystinuria type I. Hum Mol Genet. 2003 Sep 1;12(17):2109-20. Pubmed: 12923163
    9. Mayer UM: [Hyperornithinaemia in patients with retinal dystrophy] Ophthalmologe. 2003 Jan;100(1):55-61. Pubmed: 12557027
    10. Gray RG, Green A, Hall S, McKeown C: Prenatal exclusion of the HHH syndrome. Prenat Diagn. 1995 May;15(5):474-6. Pubmed: 7644438
    11. Jensen TG, Sullivan DM, Morgan RA, Taichman LB, Nussenblatt RB, Blaese RM, Csaky KG: Retrovirus-mediated gene transfer of ornithine-delta-aminotransferase into keratinocytes from gyrate atrophy patients. Hum Gene Ther. 1997 Nov 20;8(17):2125-32. Pubmed: 9414260
    12. Sell DR, Monnier VM: Ornithine is a novel amino acid and a marker of arginine damage by oxoaldehydes in senescent proteins. Ann N Y Acad Sci. 2005 Jun;1043:118-28. Pubmed: 16037230
    13. Stadler S, Gempel K, Bieger I, Pontz BF, Gerbitz KD, Bauer MF, Hofmann S: Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry. J Inherit Metab Dis. 2001 Jun;24(3):370-8. Pubmed: 11486903
    14. Gokmen SS, Aygit AC, Ayhan MS, Yorulmaz F, Gulen S: Significance of arginase and ornithine in malignant tumors of the human skin. J Lab Clin Med. 2001 May;137(5):340-4. Pubmed: 11329531
    15. Morizono H, Woolston JE, Colombini M, Tuchman M: The use of yeast mitochondria to study the properties of wild-type and mutant human mitochondrial ornithine transporter. Mol Genet Metab. 2005 Dec;86(4):431-40. Epub 2005 Oct 26. Pubmed: 16256388

    Enzymes

    General function:
    Involved in arginase activity
    Specific function:
    Not Available
    Gene Name:
    ARG1
    Uniprot ID:
    P05089
    Molecular weight:
    34734.655
    Reactions
    L-Arginine + Water → Ornithine + Ureadetails
    References
    1. Gobert AP, Cheng Y, Wang JY, Boucher JL, Iyer RK, Cederbaum SD, Casero RA Jr, Newton JC, Wilson KT: Helicobacter pylori induces macrophage apoptosis by activation of arginase II. J Immunol. 2002 May 1;168(9):4692-700. Pubmed: 11971019
    2. Iwata S, Tsujino T, Ikeda Y, Ishida T, Ueyama T, Gotoh T, Mori M, Yokoyama M: Decreased expression of arginase II in the kidneys of Dahl salt-sensitive rats. Hypertens Res. 2002 May;25(3):411-8. Pubmed: 12135320
    3. Stickings P, Mistry SK, Boucher JL, Morris SM, Cunningham JM: Arginase expression and modulation of IL-1beta-induced nitric oxide generation in rat and human islets of Langerhans. Nitric Oxide. 2002 Dec;7(4):289-96. Pubmed: 12446178
    4. Bansal V, Ochoa JB: Arginine availability, arginase, and the immune response. Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):223-8. Pubmed: 12589193
    5. El Alami M, Dubois E, Oudjama Y, Tricot C, Wouters J, Stalon V, Messenguy F: Yeast epiarginase regulation, an enzyme-enzyme activity control: identification of residues of ornithine carbamoyltransferase and arginase responsible for enzyme catalytic and regulatory activities. J Biol Chem. 2003 Jun 13;278(24):21550-8. Epub 2003 Apr 4. Pubmed: 12679340
    General function:
    Involved in transaminase activity
    Specific function:
    Not Available
    Gene Name:
    OAT
    Uniprot ID:
    P04181
    Molecular weight:
    48534.39
    Reactions
    Ornithine + a 2-oxo acid → L-Glutamic gamma-semialdehyde + an L-amino aciddetails
    Ornithine + Oxoglutaric acid → L-Glutamic gamma-semialdehyde + L-Glutamic aciddetails
    References
    1. Levillain O, Balvay S, Peyrol S: Localization and differential expression of arginase II in the kidney of male and female mice. Pflugers Arch. 2005 Feb;449(5):491-503. Epub 2004 Dec 23. Pubmed: 15616821
    2. Inubushi T, Takasawa T, Tuboi Y, Watanabe N, Aki K, Katunuma N: Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. Biofactors. 2005;23(2):59-67. Pubmed: 16179747
    3. Kaneko S, Ueda-Yamada M, Ando A, Matsumura S, Okuda-Ashitaka E, Matsumura M, Uyama M, Ito S: Cytotoxic effect of spermine on retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):455-63. Pubmed: 17197567
    General function:
    Amino acid transport and metabolism
    Specific function:
    Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.
    Gene Name:
    GATM
    Uniprot ID:
    P50440
    Molecular weight:
    48455.01
    Reactions
    L-Arginine + Glycine → Ornithine + Guanidoacetic aciddetails
    L-Arginine + Gamma-Aminobutyric acid → Ornithine + 4-Guanidinobutanoic aciddetails
    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
    3. Thomasset N, Quash GA, Dore JF: The differential contribution of arginase and transamidinase to ornithine biosynthesis in two achromic human melanoma cell lines. FEBS Lett. 1982 Nov 1;148(1):63-6. Pubmed: 7173402
    4. Natesan S, Reddy SR: Compensatory changes in enzymes of arginine metabolism during renal hypertrophy in mice. Comp Biochem Physiol B Biochem Mol Biol. 2001 Dec;130(4):585-95. Pubmed: 11691635
    5. Mitruka BM, Costilow RN: Arginine and ornithine catabolism by Clostridium botulinum. J Bacteriol. 1967 Jan;93(1):295-301. Pubmed: 5335895
    General function:
    Involved in metallopeptidase activity
    Specific function:
    Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate).
    Gene Name:
    ACY1
    Uniprot ID:
    Q03154
    Molecular weight:
    45884.705
    Reactions
    N-Acetylornithine + Water → Acetic acid + Ornithinedetails
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.
    Gene Name:
    ALDH18A1
    Uniprot ID:
    P54886
    Molecular weight:
    87088.29
    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. Barcelona-Andres B, Marina A, Rubio V: Gene structure, organization, expression, and potential regulatory mechanisms of arginine catabolism in Enterococcus faecalis. J Bacteriol. 2002 Nov;184(22):6289-300. Pubmed: 12399499
    2. El Alami M, Dubois E, Oudjama Y, Tricot C, Wouters J, Stalon V, Messenguy F: Yeast epiarginase regulation, an enzyme-enzyme activity control: identification of residues of ornithine carbamoyltransferase and arginase responsible for enzyme catalytic and regulatory activities. J Biol Chem. 2003 Jun 13;278(24):21550-8. Epub 2003 Apr 4. Pubmed: 12679340
    3. Templeton MD, Reinhardt LA, Collyer CA, Mitchell RE, Cleland WW: Kinetic analysis of the L-ornithine transcarbamoylase from Pseudomonas savastanoi pv. phaseolicola that is resistant to the transition state analogue (R)-N delta-(N'-sulfodiaminophosphinyl)-L-ornithine. Biochemistry. 2005 Mar 22;44(11):4408-15. Pubmed: 15766270
    4. 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 catalytic activity
    Specific function:
    Not Available
    Gene Name:
    ODC1
    Uniprot ID:
    P11926
    Molecular weight:
    51147.73
    Reactions
    Ornithine → Putrescine + CO(2)details
    Ornithine → Putrescine + Carbon dioxidedetails
    General function:
    Involved in arginase activity
    Specific function:
    May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to NO synthase. Since NO synthase is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase II plays a role in both male and female sexual arousal. It is therefore a potential target for the treatment of male and female sexual arousal disorders.
    Gene Name:
    ARG2
    Uniprot ID:
    P78540
    Molecular weight:
    38577.515
    Reactions
    L-Arginine + Water → Ornithine + Ureadetails
    References
    1. Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC: L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol. 2003 Aug 1;171(3):1232-9. Pubmed: 12874210
    2. Levillain O, Hus-Citharel A, Garvi S, Peyrol S, Reymond I, Mutin M, Morel F: Ornithine metabolism in male and female rat kidney: mitochondrial expression of ornithine aminotransferase and arginase II. Am J Physiol Renal Physiol. 2004 Apr;286(4):F727-38. Epub 2004 Feb 10. Pubmed: 14871882
    3. Levillain O, Diaz JJ, Blanchard O, Dechaud H: Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney. Endocrinology. 2005 Feb;146(2):950-9. Epub 2004 Nov 11. Pubmed: 15539552
    4. Bussiere FI, Chaturvedi R, Cheng Y, Gobert AP, Asim M, Blumberg DR, Xu H, Kim PY, Hacker A, Casero RA Jr, Wilson KT: Spermine causes loss of innate immune response to Helicobacter pylori by inhibition of inducible nitric-oxide synthase translation. J Biol Chem. 2005 Jan 28;280(4):2409-12. Epub 2004 Nov 17. Pubmed: 15548540
    5. Nissim I, Luhovyy B, Horyn O, Daikhin Y, Nissim I, Yudkoff M: The role of mitochondrially bound arginase in the regulation of urea synthesis: studies with [U-15N4]arginine, isolated mitochondria, and perfused rat liver. J Biol Chem. 2005 May 6;280(18):17715-24. Epub 2005 Mar 7. Pubmed: 15753084
    General function:
    Involved in transport
    Specific function:
    Involved in the transport of the cationic amino acids (arginine, lysine and ornithine)
    Gene Name:
    SLC7A4
    Uniprot ID:
    O43246
    Molecular weight:
    68267.2
    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 transporter activity
    Specific function:
    Ornithine transport across inner mitochondrial membrane, from the cytoplasm to the matrix.
    Gene Name:
    SLC25A15
    Uniprot ID:
    Q9Y619
    Molecular weight:
    32735.96
    References
    1. Korman SH, Kanazawa N, Abu-Libdeh B, Gutman A, Tsujino S: Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome with evidence of mitochondrial dysfunction due to a novel SLC25A15 (ORNT1) gene mutation in a Palestinian family. J Neurol Sci. 2004 Mar 15;218(1-2):53-8. Pubmed: 14759633
    2. Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD: Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res. 2006 Oct;60(4):423-9. Epub 2006 Aug 28. Pubmed: 16940241
    General function:
    Involved in transporter activity
    Specific function:
    Ornithine transport across inner mitochondrial membrane, from the cytoplasm to the matrix.
    Gene Name:
    SLC25A2
    Uniprot ID:
    Q9BXI2
    Molecular weight:
    32580.07
    References
    1. Camacho JA, Rioseco-Camacho N, Andrade D, Porter J, Kong J: Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder. Mol Genet Metab. 2003 Aug;79(4):257-71. Pubmed: 12948741
    2. Begum L, Jalil MA, Kobayashi K, Iijima M, Li MX, Yasuda T, Horiuchi M, del Arco A, Satrustegui J, Saheki T: Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine transporter, in relation to urea cycle in mice. Biochim Biophys Acta. 2002 Apr 12;1574(3):283-92. Pubmed: 11997094
    3. Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD: Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res. 2006 Oct;60(4):423-9. Epub 2006 Aug 28. Pubmed: 16940241
    General function:
    Involved in transport
    Specific function:
    Mediates the uptake of the cationic amino acids arginine, lysine and ornithine in a sodium-independent manner
    Gene Name:
    SLC7A3
    Uniprot ID:
    Q8WY07
    Molecular weight:
    67168.3
    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
    3. Hosokawa H, Sawamura T, Kobayashi S, Ninomiya H, Miwa S, Masaki T: Cloning and characterization of a brain-specific cationic amino acid transporter. J Biol Chem. 1997 Mar 28;272(13):8717-22. Pubmed: 9079705
    General function:
    Involved in transport
    Specific function:
    High-affinity, low capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues. May also function as an ecotropic retroviral leukemia receptor
    Gene Name:
    SLC7A1
    Uniprot ID:
    P30825
    Molecular weight:
    67637.6
    References
    1. Rotmann A, Strand D, Martine U, Closs EI: Protein kinase C activation promotes the internalization of the human cationic amino acid transporter hCAT-1. A new regulatory mechanism for hCAT-1 activity. J Biol Chem. 2004 Dec 24;279(52):54185-92. Epub 2004 Oct 15. Pubmed: 15491978
    2. Cerec V, Piquet-Pellorce C, Aly HA, Touzalin AM, Jegou B, Bauche F: Multiple pathways for cationic amino acid transport in rat seminiferous tubule cells. Biol Reprod. 2007 Feb;76(2):241-9. Epub 2006 Oct 25. Pubmed: 17065601
    3. Yeramian A, Martin L, Arpa L, Bertran J, Soler C, McLeod C, Modolell M, Palacin M, Lloberas J, Celada A: Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur J Immunol. 2006 Jun;36(6):1516-26. Pubmed: 16703566
    General function:
    Involved in transport
    Specific function:
    Low-affinity, high capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine). Plays a regulatory role in classical or alternative activation of macrophages
    Gene Name:
    SLC7A2
    Uniprot ID:
    P52569
    Molecular weight:
    71672.2
    References
    1. Yeramian A, Martin L, Arpa L, Bertran J, Soler C, McLeod C, Modolell M, Palacin M, Lloberas J, Celada A: Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur J Immunol. 2006 Jun;36(6):1516-26. Pubmed: 16703566
    2. Cerec V, Piquet-Pellorce C, Aly HA, Touzalin AM, Jegou B, Bauche F: Multiple pathways for cationic amino acid transport in rat seminiferous tubule cells. Biol Reprod. 2007 Feb;76(2):241-9. Epub 2006 Oct 25. Pubmed: 17065601
    3. Endo M, Oyadomari S, Terasaki Y, Takeya M, Suga M, Mori M, Gotoh T: Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L313-21. Epub 2003 Apr 4. Pubmed: 12679322
    General function:
    Involved in transport
    Specific function:
    Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids. Requires co-expression with SLC3A2/4F2hc to mediate the uptake of arginine, leucine and glutamine. Also acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Involved in the transport of L-arginine in monocytes. Reduces uptake of ornithine in retinal pigment epithelial (RPE) cells
    Gene Name:
    SLC7A6
    Uniprot ID:
    Q92536
    Molecular weight:
    56826.9
    General function:
    Involved in enzyme inhibitor activity
    Specific function:
    Binds to, and destabilizes, ornithine decarboxylase which is then degraded. Also inhibits cellular uptake of polyamines by inactivating the polyamine uptake transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1
    Gene Name:
    OAZ1
    Uniprot ID:
    P54368
    Molecular weight:
    25405.3
    References
    1. Lopez-Contreras AJ, Lopez-Garcia C, Jimenez-Cervantes C, Cremades A, Penafiel R: Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity. J Biol Chem. 2006 Oct 13;281(41):30896-906. Epub 2006 Aug 17. Pubmed: 16916800
    2. Yamaguchi Y, Takatsuka Y, Matsufuji S, Murakami Y, Kamio Y: Characterization of a counterpart to Mammalian ornithine decarboxylase antizyme in prokaryotes. J Biol Chem. 2006 Feb 17;281(7):3995-4001. Epub 2005 Dec 14. Pubmed: 16354653
    3. Janne J, Alhonen L, Pietila M, Keinanen TA: Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem. 2004 Mar;271(5):877-94. Pubmed: 15009201
    General function:
    Involved in enzyme inhibitor activity
    Specific function:
    Binds to, and destabilizes, ornithine decarboxylase. Does not accelerate ornithine decarboxylase degeneration
    Gene Name:
    OAZ2
    Uniprot ID:
    O95190
    Molecular weight:
    21010.9
    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 enzyme inhibitor activity
    Specific function:
    Binds to, and destabilizes, ornithine decarboxylase. Does not accelerate ornithine decarboxylase degeneration. OAZ3 probably plays a key role in spermatogenesis by regulating the intracellular concentration of polyamines in haploid germ cells
    Gene Name:
    OAZ3
    Uniprot ID:
    Q9UMX2
    Molecular weight:
    21374.8
    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 catalytic activity
    Specific function:
    Regulates cellular polyamine homeostasis. Inhibits antizyme-dependent ornithine decarboxylase degradation by binding to antizyme
    Gene Name:
    AZIN1
    Uniprot ID:
    O14977
    Molecular weight:
    49534.8