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Identification
NameL-Arginine
Accession NumberDB00125  (NUTR00014)
Typesmall molecule
Groupsapproved, nutraceutical
Description

An essential amino acid that is physiologically active in the L-form. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-2-amino-5-guanidinopentanoic acidNot AvailableNot Available
(S)-2-Amino-5-guanidinovaleric acidNot AvailableNot Available
ArgNot AvailableNot Available
L-(+)-ArginineNot AvailableNot Available
L-ArgNot AvailableNot Available
Salts
Name/CAS Structure Properties
L-Arginine Hydrochloride
Thumb Not applicable DBSALT000869
Brand names
NameCompany
R-Gene 10Pharmacia Corp.
Brand mixturesNot Available
Categories
CAS number74-79-3
WeightAverage: 174.201
Monoisotopic: 174.111675712
Chemical FormulaC6H14N4O2
InChI KeyODKSFYDXXFIFQN-BYPYZUCNSA-N
InChI
InChI=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
IUPAC Name
(2S)-2-amino-5-carbamimidamidopentanoic acid
SMILES
N[C@@H](CCCNC(N)=N)C(O)=O
Mass Specshow(2.96 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acids and Derivatives
Alternative parentsAmino Fatty Acids; Guanidines; Enolates; Amidines; Polyamines; Carboxylic Acids; Monoalkylamines
Substituentsguanidine; carboxylic acid; enolate; amidine; polyamine; amine; primary amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Pharmacology
IndicationUsed for nutritional supplementation, also for treating dietary shortage or imbalance.
PharmacodynamicsStudies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.
Mechanism of actionMany 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.
AbsorptionAbsorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Some 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.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityOral supplementation with L-arginine at doses up to 15 grams daily are generally well tolerated. The most common adverse reactions of higher doses from 15 to 30 grams daily are nausea, abdominal cramps and diarrhea. Some may experience these symptoms at lower doses.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8289
Blood Brain Barrier + 0.6882
Caco-2 permeable - 0.7316
P-glycoprotein substrate Non-substrate 0.5564
P-glycoprotein inhibitor I Non-inhibitor 0.9814
P-glycoprotein inhibitor II Non-inhibitor 0.8803
Renal organic cation transporter Non-inhibitor 0.7475
CYP450 2C9 substrate Non-substrate 0.7822
CYP450 2D6 substrate Non-substrate 0.6787
CYP450 3A4 substrate Non-substrate 0.8105
CYP450 1A2 substrate Non-inhibitor 0.8555
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.7705
CYP450 3A4 substrate Non-inhibitor 0.8925
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9945
Ames test AMES toxic 0.7182
Carcinogenicity Non-carcinogens 0.9229
Biodegradation Ready biodegradable 0.8394
Rat acute toxicity 1.4851 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9533
hERG inhibition (predictor II) Non-inhibitor 0.9683
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
Prices
Unit descriptionCostUnit
Arginine 100% crystals0.51USDg
L-arginine mhc powder0.39USDg
Arginine-500 mg tablet0.12USDtablet
Arginine 500 mg tablet0.09USDtablet
L-arginine 1000 mg tablet0.07USDtablet
R-gene 10 vial0.04USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point244 dec °CPhysProp
water solubility1.82E+005 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-4.20HANSCH,C ET AL. (1995)
pKa2.24 (at 0 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
water solubility2.28e+00 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 area125.22ChemAxon
rotatable bond count5ChemAxon
refractivity53.92ChemAxon
polarizability17.8ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
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.

US4086137
General Reference
  1. Morris SM Jr: Enzymes of arginine metabolism. J Nutr. 2004 Oct;134(10 Suppl):2743S-2747S; discussion 2765S-2767S. Pubmed
  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. Pubmed
  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. Pubmed
External Links
ResourceLink
KEGG DrugD02982
KEGG CompoundC00062
BindingDB21959
ChEBI16467
ChEMBLCHEMBL1485
PharmGKBPA448478
IUPHAR721
Guide to Pharmacology721
HETARG
Drugs.comhttp://www.drugs.com/npc/l-arginine.html
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lar_0024.shtml
WikipediaL-Arginine
ATC CodesB05XB01
AHFS Codes
  • 36:66.00
PDB Entries
FDA labelNot Available
MSDSshow(72.8 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Nitric oxide synthase, endothelial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nitric oxide synthase, endothelial P29474 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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 NADH oxidase and uncoupled endothelial nitric oxide synthase. Arthritis Rheum. 2006 Jun;54(6):1847-55. Pubmed

2. Cationic amino acid transporter 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cationic amino acid transporter 3 Q8WY07 Details

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. Pubmed
  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. Pubmed

3. Arginine decarboxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Arginine decarboxylase Q96A70 Details

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. Pubmed
  2. Regunathan S: Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence. AAPS J. 2006 Jul 21;8(3):E479-84. Pubmed
  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. Pubmed
  4. Wu N, Su RB, Li J: Agmatine and Imidazoline Receptors: Their Role in Opioid Analgesia, Tolerance and Dependence. Cell Mol Neurobiol. 2007 Jul 25;. Pubmed

4. Argininosuccinate lyase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Argininosuccinate lyase P04424 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

5. Nitric oxide synthase, inducible

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nitric oxide synthase, inducible P35228 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. 2007 Jul;85(7):723-32. Epub 2007 Mar 6. Pubmed
  5. Popovic PJ, Zeh HJ 3rd, Ochoa JB: Arginine and immunity. J Nutr. 2007 Jun;137(6 Suppl 2):1681S-1686S. Pubmed

6. High affinity cationic amino acid transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity cationic amino acid transporter 1 P30825 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

7. Arginase-2, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Arginase-2, mitochondrial P78540 Details

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. Pubmed
  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. Pubmed

8. Cationic amino acid transporter 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cationic amino acid transporter 4 O43246 Details

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. Pubmed

9. Argininosuccinate synthase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Argininosuccinate synthase P00966 Details

References:

  1. Feun L, Savaraj N: Pegylated arginine deiminase: a novel anticancer enzyme agent. Expert Opin Investig Drugs. 2006 Jul;15(7):815-22. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

Transporters

1. Solute carrier family 22 member 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 5 O76082 Details

References:

  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

2. Monocarboxylate transporter 10

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 10 Q8TF71 Details

References:

  1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. Pubmed

3. Solute carrier family 22 member 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 4 Q9H015 Details

References:

  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08