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Record Information
Version3.6
Creation Date2006-08-13 14:44:13 UTC
Update Date2013-05-29 19:39:57 UTC
HMDB IDHMDB04224
Secondary Accession NumbersNone
Metabolite Identification
Common NameN-(o)-Hydroxyarginine
DescriptionN(omega)-hydroxyarginine is a product of the arginine-Nitric Oxide pathway, and is the first intermediate in the process catalyzed by nitric oxide synthase (EC 1.14.13.99, NOS, a heme protein that catalyzes the oxygenation of L-arginine in the presence of NADPH to form nitric oxide + citrulline). N(omega)-hydroxyarginine appears to interfere with cell proliferation/cell growth by inhibiting arginase (EC 3.5.3.1, a binuclear Mn (2+) metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea), and that has 6R-tetrahydrobiopterin (H4B) as an enzyme-bound cofactor. (PMID: 11259671 , 11258880 , 14504282 , 9735327 ).
Structure
Thumb
Synonyms
  1. N-(G)-Hydroxyarginine
  2. N-(Omega)-Hydroxyarginine
Chemical FormulaC6H14N4O3
Average Molecular Weight190.2004
Monoisotopic Molecular Weight190.106590334
IUPAC Name2-amino-5-[(E)-[amino(hydroxyamino)methylidene]amino]pentanoic acid
Traditional Name2-amino-5-[(E)-[amino(hydroxyamino)methylidene]amino]pentanoic acid
CAS Registry NumberNot Available
SMILES
NC(CCC\N=C(/N)NO)C(O)=O
InChI Identifier
InChI=1S/C6H14N4O3/c7-4(5(11)12)2-1-3-9-6(8)10-13/h4,13H,1-3,7H2,(H,11,12)(H3,8,9,10)
InChI KeyFQWRAVYMZULPNK-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids
Alternative Parents
Substituents
  • Alpha-amino acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • N-hydroxyguanidine
  • Guanidine
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP-2.567Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.7 mg/mLALOGPS
logP-3.6ALOGPS
logP-3.5ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)2.2ChemAxon
pKa (Strongest Basic)10.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area133.96 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity55.89 m3·mol-1ChemAxon
Polarizability18.89 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023337
KNApSAcK IDNot Available
Chemspider ID389691
KEGG Compound IDC05933
BioCyc IDNot Available
BiGG ID46955
Wikipedia LinkNot Available
NuGOwiki LinkHMDB04224
Metagene LinkHMDB04224
METLIN IDNot Available
PubChem Compound440849
PDB IDNot Available
ChEBI ID7101
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Ignarro LJ, Buga GM, Wei LH, Bauer PM, Wu G, del Soldato P: Role of the arginine-nitric oxide pathway in the regulation of vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4202-8. Epub 2001 Mar 20. [11259671 ]
  2. Cox JD, Cama E, Colleluori DM, Pethe S, Boucher JL, Mansuy D, Ash DE, Christianson DW: Mechanistic and metabolic inferences from the binding of substrate analogues and products to arginase. Biochemistry. 2001 Mar 6;40(9):2689-701. [11258880 ]
  3. Wei CC, Wang ZQ, Hemann C, Hille R, Stuehr DJ: A tetrahydrobiopterin radical forms and then becomes reduced during Nomega-hydroxyarginine oxidation by nitric-oxide synthase. J Biol Chem. 2003 Nov 21;278(47):46668-73. Epub 2003 Sep 22. [14504282 ]
  4. Witteveen CF, Giovanelli J, Yim MB, Gachhui R, Stuehr DJ, Kaufman S: Reactivity of the flavin semiquinone of nitric oxide synthase in the oxygenation of arginine to NG-hydroxyarginine, the first step of nitric oxide synthesis. Biochem Biophys Res Commun. 1998 Sep 8;250(1):36-42. [9735327 ]

Enzymes

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
NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
L-Arginine + Oxygen + NADPH + Hydrogen Ion → N-(o)-Hydroxyarginine + NADP + Waterdetails
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
NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
L-Arginine + Oxygen + NADPH + Hydrogen Ion → N-(o)-Hydroxyarginine + NADP + Waterdetails
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
NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
L-Arginine + Oxygen + NADPH + Hydrogen Ion → N-(o)-Hydroxyarginine + NADP + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
NOS1
Uniprot ID:
B3VK56
Molecular weight:
160969.1