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targets (9) transporters (3)
for drugs
Identification
Name L-Arginine
Accession Number DB00125 (NUTR00014)
Type small molecule
Groups approved, nutraceutical
Description

An essential amino acid that is physiologically active in the L-form. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(S)-2-Amino-5-guanidinovaleric acid
Arg
L-(+)-Arginine
L-Arg
Salts Not Available
Brand names
Name Company
Argamine
Argivene
Detoxargin
Levargin
Minophagen A
R-Gene 10 Pharmacia Corp.
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
  • Conditionally Essential Amino Acids
CAS number 74-79-3
Weight Average: 174.201
Monoisotopic: 174.111675712
Chemical Formula C6H14N4O2
InChI Key InChIKey=ODKSFYDXXFIFQN-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
Plain Text
IUPAC Name
(2S)-2-amino-5-carbamimidamidopentanoic acid
SMILES
N[C@@H](CCCNC(N)=N)C(O)=O
Plain Text
Mass Spec show (2.96 KB)
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Guanidines
  • Carboxamidines
Pharmacology
Indication Used for nutritional supplementation, also for treating dietary shortage or imbalance.
Pharmacodynamics Studies 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 action Many 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.
Absorption Absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.
Volume of distribution Not Available
Protein binding Not 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 elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Oral 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices
Unit description Cost Unit
Arginine 100% crystals 0.51 USD g
L-arginine mhc powder 0.39 USD g
Arginine-500 mg tablet 0.12 USD tablet
Arginine 500 mg tablet 0.09 USD tablet
L-arginine 1000 mg tablet 0.07 USD tablet
R-gene 10 vial 0.04 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 244 dec °C PhysProp
water solubility 1.82E+005 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP -4.20 HANSCH,C ET AL. (1995)
pKa 2.24 (at 0 °C) KORTUM,G ET AL (1961)
Predicted Properties
Property Value Source
water solubility 2.28e+00 g/l ALOGPS
logP -3.5 ALOGPS
logP -3.2 ChemAxon
logS -1.9 ALOGPS
pKa (strongest acidic) 2.41 ChemAxon
pKa (strongest basic) 12.41 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 125.22 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 53.92 ChemAxon
polarizability 17.94 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D02982 Link_out
KEGG Compound C00062 Link_out
PubChem Compound 6322 Link_out
PubChem Substance 46507180 Link_out
ChemSpider 6082 Link_out
BindingDB 21959 Link_out
ChEBI 16467 Link_out
ChEMBL 16467 Link_out
PharmGKB PA448478 Link_out
IUPHAR 721 Link_out
Guide to Pharmacology 721 Link_out
HET ARG Link_out
Drugs.com http://www.drugs.com/npc/l-arginine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lar_0024.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/L-Arginine Link_out
ATC Codes
  • B05XB01
AHFS Codes
  • 36:66.00
PDB Entries
FDA label Not Available
MSDS show (72.8 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Nitric-oxide synthase, endothelial

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P29474 Link_out
Gene: NOS3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Mediates the uptake of the cationic amino acids arginine, lysine and ornithine in a sodium-independent manner

Organism class: human
UniProt ID: Q8WY07 Link_out
Gene: SLC7A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Decarboxylates L-arginine to agmatine. Truncated splice isoforms probably lack activity

Organism class: human
UniProt ID: Q96A70 Link_out
Gene: ADC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Organism class: human
UniProt ID: P04424 Link_out
Gene: ASL Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions

Organism class: human
UniProt ID: P35228 Link_out
Gene: NOS2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P30825 Link_out
Gene: SLC7A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P78540 Link_out
Gene: ARG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Involved in the transport of the cationic amino acids (arginine, lysine and ornithine)

Organism class: human
UniProt ID: O43246 Link_out
Gene: SLC7A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Organism class: human
UniProt ID: P00966 Link_out
Gene: ASS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Organic cation/carnitine transporter 2

Actions: inhibitor

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out
Gene: SLC22A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells (By similarity)

UniProt ID: Q8TF71 Link_out
Gene: SLC16A10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Organic cation/carnitine transporter 1

Actions: inhibitor

Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19