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L-arginine is a basic amino acid with a guanidino sidechain. As an amino acid, metabolism of L-arginine to form L-ornithine, catalysed by arginase, forms the last step of the urea production cycle. L-Ornithine may be utilised as a precursor of polyamines (see Carboxylases and Decarboxylases) or recycled via L-argininosuccinic acid to L-arginine. L-Arginine may itself be decarboxylated to form agmatine, although the prominence of this pathway in human tissues is uncertain. L-Arginine may be used as a precursor for guanidoacetic acid formation in the creatine synthesis pathway under the influence of arginine:glycine amidinotransferase with L-ornithine as a byproduct. Nitric oxide synthase uses L-arginine to generate nitric oxide, with L-citrulline also as a byproduct.
L-Arginine in proteins may be subject to post-translational modification through methylation, catalysed by protein arginine methyltransferases. Subsequent proteolysis can liberate asymmetric NG,NG-dimethyl-L-arginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase activities. ADMA is hydrolysed by dimethylarginine dimethylhydrolase activities to generate L-citrulline and dimethylamine.
* Key recommended reading is highlighted with an asterisk
Ataya B, Tzeng E, Zuckerbraun BS. (2011) Nitrite-generated nitric oxide to protect against intimal hyperplasia formation. Trends Cardiovasc. Med., 21 (6): 157-62. [PMID:22814422]
Di Lorenzo A, Bedford MT. (2011) Histone arginine methylation. FEBS Lett., 585 (13): 2024-31. [PMID:21074527]
Förstermann U, Li H. (2011) Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling. Br. J. Pharmacol., 164 (2): 213-23. [PMID:21198553]
Förstermann U, Sessa WC. (2012) Nitric oxide synthases: regulation and function. Eur. Heart J., 33 (7): 829-37, 837a-837d. [PMID:21890489]
Heinrich TA, da Silva RS, Miranda KM, Switzer CH, Wink DA, Fukuto JM. (2013) Biological nitric oxide signalling: chemistry and terminology. Br. J. Pharmacol., 169 (7): 1417-29. [PMID:23617570]
Karkhanis V, Hu YJ, Baiocchi RA, Imbalzano AN, Sif S. (2011) Versatility of PRMT5-induced methylation in growth control and development. Trends Biochem. Sci., 36 (12): 633-41. [PMID:21975038]
Leiper J, Nandi M. (2011) The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nat Rev Drug Discov, 10 (4): 277-91. [PMID:21455237]
* Moncada S, Higgs A, Furchgott R. (1997) International Union of Pharmacology Nomenclature in Nitric Oxide Research. Pharmacol. Rev., 49 (2): 137-42. [PMID:9228663]
* Tang L, Wang H, Ziolo MT. (2014) Targeting NOS as a therapeutic approach for heart failure. Pharmacol. Ther., 142 (3): 306-15. [PMID:24380841]
* Tratsiakovich Y, Yang J, Gonon AT, Sjöquist PO, Pernow J. (2013) Arginase as a target for treatment of myocardial ischemia-reperfusion injury. Eur. J. Pharmacol., 720 (1-3): 121-3. [PMID:24183975]
* Whiteley CG. (2014) Arginine metabolising enzymes as targets against Alzheimers' disease. Neurochem. Int., 67: 23-31. [PMID:24508404]
* Yang Y, Bedford MT. (2013) Protein arginine methyltransferases and cancer. Nat. Rev. Cancer, 13 (1): 37-50. [PMID:23235912]
Zhang YH, Jin CZ, Jang JH, Wang Y. (2014) Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. J. Physiol. (Lond.), 592 (Pt 15): 3189-200. [PMID:24756636]
Database page citation:
L-Arginine turnover. Accessed on 24/04/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=239.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.