L-Arginine (T3D4289)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2014-08-29 06:15:57 UTC
Update Date2014-12-24 20:26:45 UTC
Accession NumberT3D4289
Identification
Common NameL-Arginine
ClassSmall Molecule
DescriptionArginine is an essential amino acid that is physiologically active in the L-form. In mammals, arginine is formally classified as a semiessential or conditionally essential amino acid, depending on the developmental stage and health status of the individual. Infants are unable to effectively synthesize arginine, making it nutritionally essential for infants. Adults, however, are able to synthesize arginine in the urea cycle. Arginine can be considered to be a basic amino acid as the part of the side chain nearest to the backbone is long, carbon-containing and hydrophobic, whereas the end of the side chain is a complex guanidinium group. With a pKa of 12.48, the guanidinium group is positively charged in neutral, acidic and even most basic environments. Because of the conjugation between the double bond and the nitrogen lone pairs, the positive charge is delocalized. This group is able to form multiple H-bonds. L-arginine is an amino acid that has numerous functions in the body. It helps dispose of ammonia, is used to make compounds such as nitric oxide, creatine, L-glutamate, L-proline, and it can be converted to glucose and glycogen if needed. In large doses, L-arginine also stimulates the release of hormones growth hormone and prolactin. Arginine is a known inducer of mTOR (mammalian target of rapamycin) and is responsible for inducing protein synthesis through the mTOR pathway. mTOR inhibition by rapamycin partially reduces arginine-induced protein synthesis (18). Catabolic disease states such as sepsis, injury, and cancer cause an increase in arginine utilization, which can exceed normal body production, leading to arginine depletion. Arginine also activates AMP kinase (AMPK) which then stimulates skeletal muscle fatty acid oxidation and muscle glucose uptake, thereby increasing insulin secretion by pancreatic beta-cells (19). Arginine is found in plant and animal proteins, such as dairy products, meat, poultry, fish, and nuts. The ratio of L-arginine to lysine is also important - soy and other plant proteins have more L-arginine than animal sources of protein.
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Conditionally Essential Amino Acid
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(2S)-2-amino-5-(Carbamimidamido)pentanoic acid
(2S)-2-amino-5-Guanidinopentanoic acid
(S)-2-amino-5-guanidinopentanoic acid
(S)-2-Amino-5-guanidinovaleric acid
(S)-2-amino-5-[(aminoiminomethyl)amino]-Pentanoate
(S)-2-amino-5-[(aminoiminomethyl)amino]-Pentanoic acid
(S)-2-Amino-5-[(aminoiminomethyl)amino]pentanoate
(S)-2-Amino-5-[(aminoiminomethyl)amino]pentanoic acid
2-Amino-5-guanidinovalerate
2-Amino-5-guanidinovaleric acid
5-[(Aminoiminomethyl)amino]-L-Norvaline
Arg
Arginine
L-(+)-Arginine
L-a-Amino-D-guanidinovalerate
L-a-Amino-D-guanidinovaleric acid
L-alpha-Amino-delta-guanidinovalerate
L-alpha-Amino-delta-guanidinovaleric acid
L-Arg
L-Arginin
N5-(aminoiminomethyl)-L-Ornithine
R
R-Gene 10
Chemical FormulaC6H14N4O2
Average Molecular Mass174.201 g/mol
Monoisotopic Mass174.112 g/mol
CAS Registry Number74-79-3
IUPAC Name(2S)-2-amino-5-carbamimidamidopentanoic acid
Traditional NameL-arginine
SMILES[H][C@](N)(CCCNC(N)=N)C(O)=O
InChI IdentifierInChI=1S/C6H14N4O2/c7-4(5(11)12)2-1-3-10-6(8)9/h4H,1-3,7H2,(H,11,12)(H4,8,9,10)/t4-/m0/s1
InChI KeyInChIKey=ODKSFYDXXFIFQN-BYPYZUCNSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentL-alpha-amino acids
Alternative Parents
Substituents
  • L-alpha-amino acid
  • Fatty acid
  • Guanidine
  • Amino acid
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Carboximidamide
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Amine
  • Hydrocarbon derivative
  • Organic oxide
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Primary aliphatic amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Adrenal Cortex
  • Bladder
  • Epidermis
  • Fibroblasts
  • Gonads
  • Intestine
  • Kidney
  • Liver
  • Muscle
  • Myelin
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Stratum Corneum
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020 map00330
Glycine and Serine MetabolismSMP00004 map00260
Transcription/TranslationSMP00019 Not Available
Urea CycleSMP00059 Not Available
ArgininemiaSMP00357 Not Available
Argininosuccinic AciduriaSMP00003 Not Available
Hyperornithinemia with gyrate atrophy (HOGA)SMP00505 Not Available
Lysinuric Protein IntoleranceSMP00197 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point244 dec°C
Boiling PointNot Available
Solubility1.82E+005 mg/L (at 25°C)
LogP-4.2
Predicted Properties
PropertyValueSource
Water Solubility2.28 g/LALOGPS
logP-3.5ALOGPS
logP-3.2ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)2.41ChemAxon
pKa (Strongest Basic)12.41ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area125.22 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity53.92 m³·mol⁻¹ChemAxon
Polarizability17.8 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0a4i-1910000000-0191c1a63652c493660b2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00di-9810000000-eb6eb73302b678cf0a242014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-00di-9700000000-e47b41cff0e873f539322014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0a4i-1920000000-8ae5af11398835d26bed2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-1910000000-0191c1a63652c493660b2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-9810000000-eb6eb73302b678cf0a242017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-9700000000-e47b41cff0e873f539322017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a4i-1920000000-8ae5af11398835d26bed2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0900000000-afc3ca93f8fbf54ec9f42017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00dl-9100000000-60db59de76b9a9b5bfc82016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-004i-8900000000-f47c4f9480612fdbc9622017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0fk9-0946231100-3d57d2304dcb33feab3f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-000i-0900000000-5b6dd6fb263ea09289fc2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-001i-0900000000-dfe35b3438d19320d8cb2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-00di-0900000000-f666ab7e5354bce67a2e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-03kd-0977452210-046c4b70bd0ec351c41d2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-014i-9000000000-2f51e43e530976d636332012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-001i-0900000000-b9ebb7ebccee1a3138882012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-00di-0900000000-5379b6fb6ea2313101f92012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-001i-0900000000-835751d54af24bd337e72012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-001i-0900000000-2d2b5fd7617ccb227bb12012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-001i-0900000000-dfe35b3438d19320d8cb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-00di-0900000000-f666ab7e5354bce67a2e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-001i-0900000000-b9ebb7ebccee1a3138882017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-00di-0900000000-5379b6fb6ea2313101f92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-001i-0900000000-835751d54af24bd337e72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-001i-0900000000-2d2b5fd7617ccb227bb12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-001i-0900000000-8e090b4f0a569ec011b32021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-001i-0900000000-647e6324d4041e9d5cc12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-d866a7f7b1bf575941ee2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-001i-1900000000-c3a3ef3d4f36277810192021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-3900000000-8c82418f7b35a97fb9b32012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00di-9000000000-19b62da79866318c52dd2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00di-9000000000-64b046d21bdcbb8d59232012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-e07b937b6867d1f622932012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-87ab853583aab2973cfb2012-08-31View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, D2O, experimental)Not Available2016-10-22View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 1H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureAbsorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.
Mechanism of ToxicityMany of supplemental 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, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.
MetabolismSome metabolism of L-arginine takes place in the enterocytes. L-arginine not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed for nutritional supplementation, also for treating dietary shortage or imbalance.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00125
HMDB IDHMDB00517
PubChem Compound ID6322
ChEMBL IDCHEMBL1485
ChemSpider ID6082
KEGG IDC00062
UniProt IDNot Available
OMIM ID
ChEBI ID16467
BioCyc IDARG
CTD IDNot Available
Stitch IDNot Available
PDB IDARG
ACToR IDNot Available
Wikipedia LinkL-Arginine
References
Synthesis Reference

Kiyoshi Nakayama, Kazumi Araki, Hajime Yoshida, “Process for the production of L-arginine by fermentation.” U.S. Patent US4086137, issued May, 1973.

MSDSLink
General References
  1. Morris SM Jr: Enzymes of arginine metabolism. J Nutr. 2004 Oct;134(10 Suppl):2743S-2747S; discussion 2765S-2767S. [15465778 ]
  2. Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gerstenblith G: L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 Jan 4;295(1):58-64. [16391217 ]
  3. Alba-Roth J, Muller OA, Schopohl J, von Werder K: Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab. 1988 Dec;67(6):1186-9. [2903866 ]
  4. Mori A, Watanabe Y, Fujimoto N: Fluorometrical analysis of guanidino compounds in human cerebrospinal fluid. J Neurochem. 1982 Feb;38(2):448-50. [7108550 ]
  5. 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. [15911239 ]
  6. Haas W, Grabe K, Geis C, Pach T, Stoll K, Fuchs M, Haberl B, Loy C: Recognition and invasion of human skin by Schistosoma mansoni cercariae: the key-role of L-arginine. Parasitology. 2002 Feb;124(Pt 2):153-67. [11860033 ]
  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. [12297216 ]
  8. Stothers L, Laher I, Christ GT: A review of the L-arginine - nitric oxide - guanylate cyclase pathway as a mediator of lower urinary tract physiology and symptoms. Can J Urol. 2003 Oct;10(5):1971-80. [14633324 ]
  9. Avogaro A, Toffolo G, Kiwanuka E, de Kreutzenberg SV, Tessari P, Cobelli C: L-arginine-nitric oxide kinetics in normal and type 2 diabetic subjects: a stable-labelled 15N arginine approach. Diabetes. 2003 Mar;52(3):795-802. [12606522 ]
  10. Kotikoski H, Moilanen E, Vapaatalo H, Aine E: Biochemical markers of the L-arginine-nitric oxide pathway in the aqueous humour in glaucoma patients. Acta Ophthalmol Scand. 2002 Apr;80(2):191-5. [11952488 ]
  11. Noris M, Todeschini M, Cassis P, Pasta F, Cappellini A, Bonazzola S, Macconi D, Maucci R, Porrati F, Benigni A, Picciolo C, Remuzzi G: L-arginine depletion in preeclampsia orients nitric oxide synthase toward oxidant species. Hypertension. 2004 Mar;43(3):614-22. Epub 2004 Jan 26. [14744923 ]
  12. Kirkeby HJ, Svane D, Poulsen J, Tottrup A, Forman A, Andersson KE: Role of the L-arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins. Acta Physiol Scand. 1993 Nov;149(3):385-92. [8310843 ]
  13. Mizutani N, Hayakawa C, Ohya Y, Watanabe K, Watanabe Y, Mori A: Guanidino compounds in hyperargininemia. Tohoku J Exp Med. 1987 Nov;153(3):197-205. [3433275 ]
  14. 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. [12834252 ]
  15. Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B: Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000 Dec;119(6):1496-505. [11113071 ]
  16. 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. [6198473 ]
  17. 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. doi: 10.1038/nature07762. [19212411 ]
  18. Bauchart-Thevret C, Cui L, Wu G, Burrin DG: Arginine-induced stimulation of protein synthesis and survival in IPEC-J2 cells is mediated by mTOR but not nitric oxide. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E899-909. doi: 10.1152/ajpendo.00068.2010. Epub 2010 Sep 14. [20841502 ]
  19. Linden KC, Wadley GD, Garnham AP, McConell GK: Effect of l-arginine infusion on glucose disposal during exercise in humans. Med Sci Sports Exerc. 2011 Sep;43(9):1626-34. doi: 10.1249/MSS.0b013e318212a317. [21311355 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Nitric oxide synthase, inducible
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-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.
Gene Name:
NOS2
Uniprot ID:
P35228
Molecular Weight:
131116.3 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation7 uMNot AvailableBindingDB 21959
References
  1. Cui YY, Tang CS, Geng B: [Restraint stress down-regulates L-Arg/NOS/NO pathway of platelet and aortic intima in rats]. Beijing Da Xue Xue Bao. 2006 Jun 18;38(3):231-5. [16778961 ]
  2. Devan BD, Pistell PJ, Daffin LW Jr, Nelson CM, Duffy KB, Bowker JL, Bharati IS, Sierra-Mercado D, Spangler EL, Ingram DK: Sildenafil citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor Nomega-nitro-L-arginine methyl ester. Eur J Pharmacol. 2007 Jun 1;563(1-3):134-40. Epub 2007 Feb 17. [17362916 ]
  3. Rotoli BM, Dall'asta V, Barilli A, D'Ippolito R, Tipa A, Olivieri D, Gazzola GC, Bussolati O: Alveolar macrophages from normal subjects lack the NOS-related system y+ for arginine transport. Am J Respir Cell Mol Biol. 2007 Jul;37(1):105-12. Epub 2007 Mar 15. [17363779 ]
  4. Kagemann G, Sies H, Schnorr O: Limited availability of L-arginine increases DNA-binding activity of NF-kappaB and contributes to regulation of iNOS expression. J Mol Med (Berl). 2007 Jul;85(7):723-32. Epub 2007 Mar 6. [17340133 ]
  5. Popovic PJ, Zeh HJ 3rd, Ochoa JB: Arginine and immunity. J Nutr. 2007 Jun;137(6 Suppl 2):1681S-1686S. [17513447 ]
  6. Martin NI, Beeson WT, Woodward JJ, Marletta MA: N(G)-aminoguanidines from primary amines and the preparation of nitric oxide synthase inhibitors. J Med Chem. 2008 Feb 28;51(4):924-31. doi: 10.1021/jm701119v. Epub 2008 Jan 26. [18220331 ]
  7. Martin NI, Woodward JJ, Winter MB, Marletta MA: 4,4-Difluorinated analogues of l-arginine and N(G)-hydroxy-l-arginine as mechanistic probes for nitric oxide synthase. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1758-62. doi: 10.1016/j.bmcl.2009.01.076. Epub 2009 Feb 18. [19230661 ]
Target Details
2. Argininosuccinate lyase
General Function:
Argininosuccinate lyase activity
Specific Function:
Not Available
Gene Name:
ASL
Uniprot ID:
P04424
Molecular Weight:
51657.505 Da
References
  1. Moradi H, Kwok V, Vaziri ND: Effect of chronic renal failure on arginase and argininosuccinate synthetase expression. Am J Nephrol. 2006;26(3):310-8. Epub 2006 Jun 29. [16809898 ]
  2. Bizzoco E, Vannucchi MG, Faussone-Pellegrini MS: Transient ischemia increases neuronal nitric oxide synthase, argininosuccinate synthetase and argininosuccinate lyase co-expression in rat striatal neurons. Exp Neurol. 2007 Mar;204(1):252-9. Epub 2007 Jan 2. [17198704 ]
  3. Mages W, Heinrich O, Treuner G, Vlcek D, Daubnerova I, Slaninova M: Complementation of the Chlamydomonas reinhardtii arg7-8 (arg2) point mutation by recombination with a truncated nonfunctional ARG7 gene. Protist. 2007 Oct;158(4):435-46. Epub 2007 Jul 3. [17611150 ]
  4. Tischner R, Galli M, Heimer YM, Bielefeld S, Okamoto M, Mack A, Crawford NM: Interference with the citrulline-based nitric oxide synthase assay by argininosuccinate lyase activity in Arabidopsis extracts. FEBS J. 2007 Aug;274(16):4238-45. Epub 2007 Jul 25. [17651442 ]
  5. Mori M: Regulation of nitric oxide synthesis and apoptosis by arginase and arginine recycling. J Nutr. 2007 Jun;137(6 Suppl 2):1616S-1620S. [17513437 ]
Target Details
3. High affinity cationic amino acid transporter 1
General Function:
L-ornithine transmembrane transporter activity
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:
67637.62 Da
References
  1. Yang Z, Venardos K, Jones E, Morris BJ, Chin-Dusting J, Kaye DM: Identification of a novel polymorphism in the 3'UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction. Circulation. 2007 Mar 13;115(10):1269-74. Epub 2007 Feb 26. [17325243 ]
  2. Rotmann A, Simon A, Martine U, Habermeier A, Closs EI: Activation of classical protein kinase C decreases transport via systems y+ and y+L. Am J Physiol Cell Physiol. 2007 Jun;292(6):C2259-68. Epub 2007 Feb 28. [17329401 ]
  3. Vasquez R, Farias M, Vega JL, Martin RS, Vecchiola A, Casanello P, Sobrevia L: D-glucose stimulation of L-arginine transport and nitric oxide synthesis results from activation of mitogen-activated protein kinases p42/44 and Smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium. J Cell Physiol. 2007 Sep;212(3):626-32. [17427197 ]
  4. 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. [17065601 ]
  5. Rotoli BM, Dall'asta V, Barilli A, D'Ippolito R, Tipa A, Olivieri D, Gazzola GC, Bussolati O: Alveolar macrophages from normal subjects lack the NOS-related system y+ for arginine transport. Am J Respir Cell Mol Biol. 2007 Jul;37(1):105-12. Epub 2007 Mar 15. [17363779 ]
Target Details
4. Nitric oxide synthase, endothelial
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 forming heterodimers with isoform 1.
Gene Name:
NOS3
Uniprot ID:
P29474
Molecular Weight:
133287.62 Da
References
  1. Akamine EH, Kawamoto EM, Scavone C, Nigro D, Carvalho MH, de Cassia A Tostes R, Britto LR, Fortes ZB: Correction of endothelial dysfunction in diabetic female rats by tetrahydrobiopterin and chronic insulin. J Vasc Res. 2006;43(4):309-20. Epub 2006 May 8. [16682803 ]
  2. Gautier C, Mikula I, Nioche P, Martasek P, Raman CS, Slama-Schwok A: Dynamics of NO rebinding to the heme domain of NO synthase-like proteins from bacterial pathogens. Nitric Oxide. 2006 Dec;15(4):312-27. Epub 2006 Apr 5. [16690332 ]
  3. Yang J, Ji R, Cheng Y, Sun JZ, Jennings LK, Zhang C: L-arginine chlorination results in the formation of a nonselective nitric-oxide synthase inhibitor. J Pharmacol Exp Ther. 2006 Sep;318(3):1044-9. Epub 2006 May 22. [16717106 ]
  4. Ishikawa T, Harada T, Koi H, Kubota T, Azuma H, Aso T: Identification of arginase in human placental villi. Placenta. 2007 Feb-Mar;28(2-3):133-8. Epub 2006 May 23. [16720041 ]
  5. Haruna Y, Morita Y, Komai N, Yada T, Sakuta T, Tomita N, Fox DA, Kashihara N: Endothelial dysfunction in rat adjuvant-induced arthritis: vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthase. Arthritis Rheum. 2006 Jun;54(6):1847-55. [16729278 ]
Target Details
5. Antizyme inhibitor 2
General Function:
Putrescine transmembrane transporter activity
Specific Function:
Antizyme inhibitor protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake by counteracting the negative effect of antizymes OAZ1, OAZ2 and OAZ3 on ODC1 activity (PubMed:17900240). Inhibits antizyme-dependent ODC1 degradation by binding to antizymes. Releases ODC1 from its inactive complex with antizymes, leading to formation of the catalytically active ODC1. Participates in the morphological integrity of the trans-Golgi network (TGN) and functions as a regulator of intracellular secretory vesicle trafficking (PubMed:20188728).
Gene Name:
AZIN2
Uniprot ID:
Q96A70
Molecular Weight:
49979.185 Da
References
  1. Kotil K, Kuscuoglu U, Kirali M, Uzun H, Akcetin M, Bilge T: Investigation of the dose-dependent neuroprotective effects of agmatine in experimental spinal cord injury: a prospective randomized and placebo-control trial. J Neurosurg Spine. 2006 May;4(5):392-9. [16703907 ]
  2. Regunathan S: Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence. AAPS J. 2006 Jul 21;8(3):E479-84. [17025265 ]
  3. Yang HQ, Gao HJ: [Physiological function of arginine and its metabolites in plants]. Zhi Wu Sheng Li Yu Fen Zi Sheng Wu Xue Xue Bao. 2007 Feb;33(1):1-8. [17287563 ]
  4. Wu N, Su RB, Li J: Agmatine and imidazoline receptors: their role in opioid analgesia, tolerance and dependence. Cell Mol Neurobiol. 2008 Aug;28(5):629-41. Epub 2007 Jul 25. [17653850 ]
Target Details
6. Argininosuccinate synthase
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. Feun L, Savaraj N: Pegylated arginine deiminase: a novel anticancer enzyme agent. Expert Opin Investig Drugs. 2006 Jul;15(7):815-22. [16787144 ]
  2. Moradi H, Kwok V, Vaziri ND: Effect of chronic renal failure on arginase and argininosuccinate synthetase expression. Am J Nephrol. 2006;26(3):310-8. Epub 2006 Jun 29. [16809898 ]
  3. Cheng PN, Lam TL, Lam WM, Tsui SM, Cheng AW, Lo WH, Leung YC: Pegylated recombinant human arginase (rhArg-peg5,000mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion. Cancer Res. 2007 Jan 1;67(1):309-17. [17210712 ]
  4. Szlosarek PW, Grimshaw MJ, Wilbanks GD, Hagemann T, Wilson JL, Burke F, Stamp G, Balkwill FR: Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer. Int J Cancer. 2007 Jul 1;121(1):6-11. [17354225 ]
Target Details
7. Arginase-2, mitochondrial
General Function:
Metal ion binding
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 Da
References
  1. Topal G, Brunet A, Walch L, Boucher JL, David-Dufilho M: Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells. J Pharmacol Exp Ther. 2006 Sep;318(3):1368-74. Epub 2006 Jun 26. [16801455 ]
  2. Hood HM, Spevak CC, Sachs MS: Evolutionary changes in the fungal carbamoyl-phosphate synthetase small subunit gene and its associated upstream open reading frame. Fungal Genet Biol. 2007 Feb;44(2):93-104. Epub 2006 Sep 18. [16979358 ]
Target Details
8. Cationic amino acid transporter 3
General Function:
L-ornithine transmembrane transporter activity
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:
67168.31 Da
References
  1. Rotmann A, Simon A, Martine U, Habermeier A, Closs EI: Activation of classical protein kinase C decreases transport via systems y+ and y+L. Am J Physiol Cell Physiol. 2007 Jun;292(6):C2259-68. Epub 2007 Feb 28. [17329401 ]
  2. Huang Y, Kang BN, Tian J, Liu Y, Luo HR, Hester L, Snyder SH: The cationic amino acid transporters CAT1 and CAT3 mediate NMDA receptor activation-dependent changes in elaboration of neuronal processes via the mammalian target of rapamycin mTOR pathway. J Neurosci. 2007 Jan 17;27(3):449-58. [17234578 ]
Target Details
9. Cationic amino acid transporter 4
General Function:
L-ornithine transmembrane transporter activity
Specific Function:
Involved in the transport of the cationic amino acids (arginine, lysine and ornithine).
Gene Name:
SLC7A4
Uniprot ID:
O43246
Molecular Weight:
68267.17 Da
References
  1. Rotmann A, Simon A, Martine U, Habermeier A, Closs EI: Activation of classical protein kinase C decreases transport via systems y+ and y+L. Am J Physiol Cell Physiol. 2007 Jun;292(6):C2259-68. Epub 2007 Feb 28. [17329401 ]