You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameL-Citrulline
Accession NumberDB00155  (NUTR00021)
TypeSmall Molecule
GroupsApproved, Nutraceutical
DescriptionCitrulline is an amino acid. It is 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. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated.
Structure
Thumb
Synonyms
(S)-2-Amino-5-ureidopentanoic acid
2-Amino-5-ureidovaleric acid
alpha-amino-delta-Ureidovaleric acid
Cit
Citrulline
delta-Ureidonorvaline
L-2-Amino-5-ureidovaleric acid
L-Citrulline
N(5)-(Aminocarbonyl)-L-ornithine
N(delta)-Carbamylornithine
N5-(Aminocarbonyl)ornithine
N5-Carbamoyl-L-ornithine
N5-carbamoylornithine
α-amino-δ-ureidovaleric acid
δ-ureidonorvaline
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII29VT07BGDA
CAS number372-75-8
WeightAverage: 175.1857
Monoisotopic: 175.095691297
Chemical FormulaC6H13N3O3
InChI KeyRHGKLRLOHDJJDR-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
IUPAC Name
(2S)-2-amino-5-(carbamoylamino)pentanoic acid
SMILES
N[C@@H](CCCNC(N)=O)C(O)=O
Pharmacology
IndicationUsed for nutritional supplementation, also for treating dietary shortage or imbalance.
Structured Indications Not Available
PharmacodynamicsA non-essential amino acid and a precursor of arginine. Citrulline supplements have been claimed to promote energy levels, stimulate the immune system and help detoxify ammonia (a cell toxin). L-citrulline is made from L-ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from L-arginine as a by-product of the reaction catalyzed by the enzyme NO synthase. L-citrulline, while being an amino acid, is not involved in protein synthesis and is not one of the amino acids coded for by DNA. Although citrulline cannot be incorporated in proteins during protein synthesis, several proteins are known to contain citrulline as an amino acid. These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases (PADs), which convert the amino acid arginine into citrulline. Proteins that contain citrulline residues include myelin basic protein (MBP), fillagrin and several histone proteins.
Mechanism of actionL-citrulline is converted to L-arginine by argininosuccinate synthase. L-arginine is in turn responsible for citrulline's therapeutic affects. Many of L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3',5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase.

NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium.

All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, L-arginine could enhance endothelial-dependent vasodilation and NO production.
TargetKindPharmacological actionActionsOrganismUniProt ID
Nitric oxide synthase, endothelialProteinunknownNot AvailableHumanP29474 details
Argininosuccinate synthaseProteinunknownNot AvailableHumanP00966 details
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2ProteinunknownNot AvailableHumanO95865 details
Argininosuccinate synthetase, isoform CRA_aProteinunknownNot AvailableHumanQ5T6L4 details
N(G),N(G)-dimethylarginine dimethylaminohydrolase 1ProteinunknownNot AvailableHumanO94760 details
Ornithine carbamoyltransferase, mitochondrialProteinunknownNot AvailableHumanP00480 details
Nitric oxide synthase, brainProteinunknownNot AvailableHumanP29475 details
Nitric oxide synthase, inducibleProteinunknownNot AvailableHumanP35228 details
Protein-arginine deiminase type-4ProteinunknownNot AvailableHumanQ9UM07 details
Protein-arginine deiminase type-6ProteinunknownNot AvailableHumanQ6TGC4 details
Protein-arginine deiminase type-1ProteinunknownNot AvailableHumanQ9ULC6 details
Protein-arginine deiminase type-3ProteinunknownNot AvailableHumanQ9ULW8 details
Protein-arginine deiminase type-2ProteinunknownNot AvailableHumanQ9Y2J8 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
HypoacetylaspartiaDiseaseSMP00192
ArgininemiaDiseaseSMP00357
Argininosuccinic AciduriaDiseaseSMP00003
Prolidase Deficiency (PD)DiseaseSMP00207
Citrullinemia Type IDiseaseSMP00001
Carbamoyl Phosphate Synthetase DeficiencyDiseaseSMP00002
Aspartate MetabolismMetabolicSMP00067
Ornithine Aminotransferase Deficiency (OAT Deficiency)DiseaseSMP00363
Arginine and Proline MetabolismMetabolicSMP00020
Urea CycleMetabolicSMP00059
Canavan DiseaseDiseaseSMP00175
Ornithine Transcarbamylase Deficiency (OTC Deficiency)DiseaseSMP00205
Prolinemia Type IIDiseaseSMP00208
Hyperprolinemia Type IDiseaseSMP00361
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)DiseaseSMP00188
Hyperprolinemia Type IIDiseaseSMP00360
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)DiseaseSMP00362
Creatine deficiency, guanidinoacetate methyltransferase deficiencyDiseaseSMP00504
Hyperornithinemia with gyrate atrophy (HOGA)DiseaseSMP00505
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]DiseaseSMP00506
L-arginine:glycine amidinotransferase deficiencyDiseaseSMP00507
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis Reference

Hua Bai, Peijie Yang, Zhengjie Chen, Chongyan Xu, Zhaorul Li, Zigang Zhao, Luyan Jiang, Zongyi Yang, Jiang Li, “PROCESSES FOR THE PRODUCTION OF L-CITRULLINE.” U.S. Patent US20090142813, issued June 04, 2009.

US20090142813
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (72.8 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6863
Blood Brain Barrier+0.8961
Caco-2 permeable-0.813
P-glycoprotein substrateNon-substrate0.616
P-glycoprotein inhibitor INon-inhibitor0.9782
P-glycoprotein inhibitor IINon-inhibitor0.982
Renal organic cation transporterNon-inhibitor0.9331
CYP450 2C9 substrateNon-substrate0.7522
CYP450 2D6 substrateNon-substrate0.7828
CYP450 3A4 substrateNon-substrate0.8127
CYP450 1A2 substrateNon-inhibitor0.9415
CYP450 2C9 inhibitorNon-inhibitor0.9149
CYP450 2D6 inhibitorNon-inhibitor0.97
CYP450 2C19 inhibitorNon-inhibitor0.9018
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9896
Ames testNon AMES toxic0.5916
CarcinogenicityNon-carcinogens0.9113
BiodegradationReady biodegradable0.9247
Rat acute toxicity1.3397 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.972
hERG inhibition (predictor II)Non-inhibitor0.9716
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
L-citrulline powder1.01USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point235.5 °CPhysProp
water solubility200 g/L (at 20 °C)Not Available
logP-3.19SANGSTER (1994)
pKa2.43 (at 25 °C)KORTUM,G ET AL (1961)
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
Spectra
Mass Spec (NIST)Not Available
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
Predicted GC-MSPredicted GC-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
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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentD-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 FrameworkAliphatic acyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Tetrahydrobiopterin binding
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 ...
Gene Name:
NOS3
Uniprot ID:
P29474
Molecular Weight:
133287.62 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Toxic substance binding
Specific Function:
Is indirectly involved in the control of blood pressure.
Gene Name:
ASS1
Uniprot ID:
P00966
Molecular Weight:
46530.055 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Dimethylargininase activity
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Toxic substance binding
Specific Function:
Not Available
Gene Name:
ASS
Uniprot ID:
Q5T6L4
Molecular Weight:
46530.055 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
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:
31121.5 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Phospholipid binding
Specific Function:
Not Available
Gene Name:
OTC
Uniprot ID:
P00480
Molecular Weight:
39934.775 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Tetrahydrobiopterin binding
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Tetrahydrobiopterin binding
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. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-n...
Gene Name:
NOS2
Uniprot ID:
P35228
Molecular Weight:
131116.3 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein-arginine deiminase activity
Specific Function:
Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as...
Gene Name:
PADI4
Uniprot ID:
Q9UM07
Molecular Weight:
74078.65 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein-arginine deiminase activity
Specific Function:
Catalyzes the deimination of arginine residues of proteins.
Gene Name:
PADI1
Uniprot ID:
Q9ULC6
Molecular Weight:
74664.97 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein-arginine deiminase activity
Specific Function:
Catalyzes the deimination of arginine residues of proteins.
Gene Name:
PADI3
Uniprot ID:
Q9ULW8
Molecular Weight:
74742.705 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein-arginine deiminase activity
Specific Function:
Catalyzes the deimination of arginine residues of proteins.
Gene Name:
PADI2
Uniprot ID:
Q9Y2J8
Molecular Weight:
75563.35 Da
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 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23