Citrulline

Identification

Generic Name
Citrulline
DrugBank Accession Number
DB00155
Background

Citrulline 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.

Type
Small Molecule
Groups
Investigational, Nutraceutical
Structure
Weight
Average: 175.1857
Monoisotopic: 175.095691297
Chemical Formula
C6H13N3O3
Synonyms
  • (S)-2-Amino-5-ureidopentanoic acid
  • 2-Amino-5-ureidovaleric acid
  • alpha-amino-delta-Ureidovaleric acid
  • Cit
  • Citrulina
  • 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

Pharmacology

Indication

Used for nutritional supplementation, also for treating dietary shortage or imbalance.

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Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

A 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 action

L-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.

TargetActionsOrganism
UNitric oxide synthase, endothelialNot AvailableHumans
UArgininosuccinate synthaseNot AvailableHumans
UN(G),N(G)-dimethylarginine dimethylaminohydrolase 2Not AvailableHumans
UN(G),N(G)-dimethylarginine dimethylaminohydrolase 1Not AvailableHumans
UOrnithine carbamoyltransferase, mitochondrialNot AvailableHumans
UNitric oxide synthase, brainNot AvailableHumans
UNitric oxide synthase, inducibleNot AvailableHumans
UProtein-arginine deiminase type-4Not AvailableHumans
NProtein-arginine deiminase type-6
product of
Humans
UProtein-arginine deiminase type-1Not AvailableHumans
UProtein-arginine deiminase type-3Not AvailableHumans
UProtein-arginine deiminase type-2Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
PathwayCategory
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)Disease
Creatine Deficiency, Guanidinoacetate Methyltransferase DeficiencyDisease
Hyperornithinemia with Gyrate Atrophy (HOGA)Disease
Carbamoyl Phosphate Synthetase DeficiencyDisease
Argininosuccinic AciduriaDisease
Arginine and Proline MetabolismMetabolic
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)Disease
Hyperprolinemia Type IIDisease
Hyperprolinemia Type IDisease
L-Arginine:Glycine Amidinotransferase DeficiencyDisease
Citrullinemia Type IDisease
Urea CycleMetabolic
Aspartate MetabolismMetabolic
Canavan DiseaseDisease
HypoacetylaspartiaDisease
Ornithine Transcarbamylase Deficiency (OTC Deficiency)Disease
Prolidase Deficiency (PD)Disease
Prolinemia Type IIDisease
ArgininemiaDisease
Ornithine Aminotransferase Deficiency (OAT Deficiency)Disease
Hyperornithinemia-Hyperammonemia-Homocitrullinuria [HHH-syndrome]Disease
Nitric Oxide Signaling PathwaySignaling
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetazolamideThe excretion of Citrulline can be decreased when combined with Acetazolamide.
Acetylsalicylic acidThe excretion of Citrulline can be decreased when combined with Acetylsalicylic acid.
AcyclovirThe excretion of Citrulline can be decreased when combined with Acyclovir.
Adefovir dipivoxilThe excretion of Citrulline can be decreased when combined with Adefovir dipivoxil.
Aminohippuric acidThe excretion of Citrulline can be decreased when combined with Aminohippuric acid.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Citrulline malatePAB4036KHO70796-17-7DROVUXYZTXCEBX-WCCKRBBISA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
STIMOL ORAL SOLUTION 1g/10mlSolution1 g/10mlOralEP PLUS GROUP SDN. BHD.2020-09-082022-01-14Malaysia flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
โปลิเลโวCitrulline (100 mg) + Arginine hydrochloride (200 mg) + Cyanocobalamin (500 mcg) + Folic acid (1 mg) + Nicotinamide (15 mg) + Ornithine hydrochloride (100 mg)Solutionบริษัท มิลลิเมด จำกัด จำกัด2012-03-08Not applicableThailand flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
LipoviteCitrulline (1 mg/1mL) + Choline (1 mg/1mL) + Chromium (1 mg/1mL) + Dexpanthenol (1 mg/1mL) + Inositol (1 mg/1mL) + Levocarnitine (1 mg/1mL) + Lidocaine (1 mg/1mL) + Mecobalamin (1 mg/1mL) + Methionine sulfoximine (1 mg/1mL) + Nicotinamide (1 mg/1mL) + Pyridoxine (1 mg/1mL) + Riboflavin (1 mg/1mL) + Thiamine chloride (1 mg/1mL)InjectionIntramuscularPerdido Key Health And Wellness Inc2015-11-23Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
L-alpha-amino acids
Alternative Parents
Fatty acids and conjugates / Isoureas / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Carboximidamides / Organopnictogen compounds / Organic oxides / Monoalkylamines / Imines
show 2 more
Substituents
Aliphatic acyclic compound / Amine / Amino acid / Carbonyl group / Carboximidamide / Carboximidic acid derivative / Carboxylic acid / Fatty acid / Hydrocarbon derivative / Imine
show 11 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
citrulline (CHEBI:16349) / Other amino acids (C00327)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
29VT07BGDA
CAS number
372-75-8
InChI Key
RHGKLRLOHDJJDR-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

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 References
Not Available
Human Metabolome Database
HMDB0000904
KEGG Drug
D07706
KEGG Compound
C00327
PubChem Compound
9750
PubChem Substance
46506583
ChemSpider
9367
BindingDB
92903
RxNav
2567
ChEBI
16349
ChEMBL
CHEMBL444814
ZINC
ZINC000001532614
PharmGKB
PA164747225
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
CIR
Wikipedia
Citrulline
PDB Entries
1h70 / 1j1z / 1j21 / 1k97 / 1kod / 1kp3 / 1lxy / 1ol1 / 1qr3 / 2c6z
show 51 more
MSDS
Download (72.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedPreventionHeart Defects,Congenital / Pulmonary Hypertension (PH)1
3CompletedPreventionLung Injury, Acute (ALI)1
3CompletedTreatmentDuchenne Muscular Dystrophy (DMD)1
3CompletedTreatmentPost-Poliomyelitis Syndrome1
3Not Yet RecruitingTreatmentMalnutrition / Severe Chronic Obstructive Pulmonary Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Medisca Inc.
Dosage Forms
FormRouteStrength
InjectionIntramuscular
SolutionOral1.000 g
SolutionOral1 g/10ml
TabletOral
Solution
Prices
Unit descriptionCostUnit
L-citrulline powder1.01USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)235.5 °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 FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)GC-MSsplash10-0a4i-0920000000-2d92b63cd5d9648023b8
GC-MS Spectrum - GC-MS (3 TMS)GC-MSsplash10-00di-9610000000-2e7cd23afc2adcef35a3
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-007o-9100000000-1f8dd2c6648b104639c7
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0a4i-0920000000-2d92b63cd5d9648023b8
GC-MS Spectrum - GC-MSGC-MSsplash10-00di-9610000000-2e7cd23afc2adcef35a3
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)LC-MS/MSsplash10-0a4i-0900000000-4c1d7af748a47e489949
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)LC-MS/MSsplash10-00di-9000000000-988fced362fc0da157c9
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)LC-MS/MSsplash10-00di-9000000000-0818e0e8bcee12692498
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-004j-0900000000-5fa8a338dcd2f2a6bdd2
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-004i-0900000000-16763200aa07f7629ad4
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-03di-3900000000-d9cfc5187aa799f6f978
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-0a4i-0900000000-10ee9a593e13550bec1c
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-004i-0900000000-45d272576af34c9512a3
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-014i-3900000000-6177a284fdea5a3f1306
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-0a4i-0900000000-d9456d45e2dbd7a3df10
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , PositiveLC-MS/MSsplash10-004i-0900000000-ada57cdc73bda93be483
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-008a-0904000000-23fbe48f82e515087d68
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-03di-5900000000-78afcbaf8b8b3eabf174
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-001i-0900000000-8fb191d4c20fd54b9282
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-00di-0900000000-da484f0362a8dca5127e
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, NegativeLC-MS/MSsplash10-00e9-0900000000-46229b4f77feabb3f857
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, NegativeLC-MS/MSsplash10-001i-0900000000-4aca1022c393602a297d
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, NegativeLC-MS/MSsplash10-001i-0900000000-3bc2eff2e907b7734cc8
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, NegativeLC-MS/MSsplash10-001i-3900000000-2613bf40e3be814da86f
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, NegativeLC-MS/MSsplash10-0006-9300000000-e83287bbc060eb9cf6f3
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, PositiveLC-MS/MSsplash10-056r-0900000000-694a8872bdfd7eec1f2b
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, PositiveLC-MS/MSsplash10-08fr-2900000000-15b4711991ea9985fb2b
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, PositiveLC-MS/MSsplash10-00di-9300000000-915fbb73e0b728420e4a
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, PositiveLC-MS/MSsplash10-00di-9000000000-67e60567f5c062728350
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, PositiveLC-MS/MSsplash10-00di-9000000000-25140713431edd7c5eea
LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , PositiveLC-MS/MSsplash10-074i-5900000000-bf58ae40ccbbcae3b59e
LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , NegativeLC-MS/MSsplash10-001i-0900000000-daf5b8d935c6f60c6df7
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00e9-0900000000-46229b4f77feabb3f857
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0900000000-4aca1022c393602a297d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0900000000-322d7f0082e7d5c6ebee
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-3900000000-2613bf40e3be814da86f
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0006-9300000000-e83287bbc060eb9cf6f3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-5900000000-78afcbaf8b8b3eabf174
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0900000000-8fb191d4c20fd54b9282
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-00di-0900000000-da484f0362a8dca5127e
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-001i-0900000000-daf5b8d935c6f60c6df7
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-001i-0900000000-20fe8593ca8d8303d73a
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-001i-0900000000-a2851fcef80bb0d9b984
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-056r-0900000000-694a8872bdfd7eec1f2b
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-08fr-2900000000-15b4711991ea9985fb2b
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9300000000-915fbb73e0b728420e4a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9000000000-67e60567f5c062728350
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9000000000-603badf565140abcd117
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-3900000000-d9cfc5187aa799f6f978
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0900000000-10ee9a593e13550bec1c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-3900000000-6177a284fdea5a3f1306
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0900000000-d9456d45e2dbd7a3df10
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0900000000-ada57cdc73bda93be483
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-074i-5900000000-bf58ae40ccbbcae3b59e
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0002-0900000000-9e195f6724ee47655efb
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0900000000-1742c58acfb2cc3f3944
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-066r-2900000000-47b0441573adf2e6a74f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0900000000-d25a9f58325be99c13db
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9400000000-b8c8843b57f83a5a91cc
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-e4d56eace6a37270037b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9000000000-f77e7fdd1ea9420c52da
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-1ec0484a4e7cc0167fe5
13C NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
[1H,1H] 2D NMR Spectrum2D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-145.7304278
predicted
DarkChem Lite v0.1.0
[M-H]-134.6028944
predicted
DarkChem Standard v0.1.0
[M-H]-145.7331278
predicted
DarkChem Lite v0.1.0
[M-H]-130.95819
predicted
DeepCCS 1.0 (2019)
[M+H]+144.9070278
predicted
DarkChem Lite v0.1.0
[M+H]+134.6671166
predicted
DarkChem Standard v0.1.0
[M+H]+144.1951278
predicted
DarkChem Lite v0.1.0
[M+H]+134.78554
predicted
DeepCCS 1.0 (2019)
[M+Na]+144.0727278
predicted
DarkChem Lite v0.1.0
[M+Na]+144.2345278
predicted
DarkChem Lite v0.1.0
[M+Na]+144.0088278
predicted
DarkChem Lite v0.1.0
[M+Na]+144.07446
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
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)-induce...
Gene Name
NOS3
Uniprot ID
P29474
Uniprot Name
Nitric oxide synthase, endothelial
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Argininosuccinate synthase
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
N(G),N(G)-dimethylarginine dimethylaminohydrolase 1
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Phospholipid binding
Specific Function
Not Available
Gene Name
OTC
Uniprot ID
P00480
Uniprot Name
Ornithine carbamoyltransferase, mitochondrial
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. P...
Gene Name
NOS1
Uniprot ID
P29475
Uniprot Name
Nitric oxide synthase, brain
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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 ...
Gene Name
NOS2
Uniprot ID
P35228
Uniprot Name
Nitric oxide synthase, inducible
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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...
Gene Name
PADI4
Uniprot ID
Q9UM07
Uniprot Name
Protein-arginine deiminase type-4
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. [Article]
  2. Wysocka J, Allis CD, Coonrod S: Histone arginine methylation and its dynamic regulation. Front Biosci. 2006 Jan 1;11:344-55. [Article]
  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. [Article]
  4. Chang X, Han J: Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. Mol Carcinog. 2006 Mar;45(3):183-96. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Product of
Curator comments
Literature referenced performed experimentation of the drug on the target in mice.
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
Uniprot Name
Protein-arginine deiminase type-6
Molecular Weight
77726.735 Da
References
  1. Snow AJ, Puri P, Acker-Palmer A, Bouwmeester T, Vijayaraghavan S, Kline D: Phosphorylation-dependent interaction of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein (YWHA) with PADI6 following oocyte maturation in mice. Biol Reprod. 2008 Aug;79(2):337-47. doi: 10.1095/biolreprod.108.069328. Epub 2008 May 7. [Article]
  2. Esposito G, Vitale AM, Leijten FP, Strik AM, Koonen-Reemst AM, Yurttas P, Robben TJ, Coonrod S, Gossen JA: Peptidylarginine deiminase (PAD) 6 is essential for oocyte cytoskeletal sheet formation and female fertility. Mol Cell Endocrinol. 2007 Jul 15;273(1-2):25-31. doi: 10.1016/j.mce.2007.05.005. Epub 2007 May 17. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Protein-arginine deiminase type-1
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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Protein-arginine deiminase type-3
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Protein-arginine deiminase type-2
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. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Substrate profile was investigated in vitro using HEK293 cells, where the reported Km value was 238 ± 13 μM.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 13, 2024 02:57