Abstract
The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme. The NO synthase had an absolute requirement for L-arginine and NADPH and did not require any other cofactors. The enzyme had a Vmax. of 42 pmol of NO formed.min-1.mg of protein-1 and a Km for L-arginine of 8.4 microM. Three analogues of L-arginine, namely NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-iminoethyl-L-ornithine inhibited the brain NO synthase. All three compounds were competitive inhibitors of the enzyme with Ki values of 0.7, 0.4 and 1.2 microM respectively.
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Selected References
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- Amber I. J., Hibbs J. B., Jr, Taintor R. R., Vavrin Z. Cytokines induce an L-arginine-dependent effector system in nonmacrophage cells. J Leukoc Biol. 1988 Jul;44(1):58–65. doi: 10.1002/jlb.44.1.58. [DOI] [PubMed] [Google Scholar]
- Barbul A. Arginine: biochemistry, physiology, and therapeutic implications. JPEN J Parenter Enteral Nutr. 1986 Mar-Apr;10(2):227–238. doi: 10.1177/0148607186010002227. [DOI] [PubMed] [Google Scholar]
- Brüne B., Lapetina E. G. Activation of a cytosolic ADP-ribosyltransferase by nitric oxide-generating agents. J Biol Chem. 1989 May 25;264(15):8455–8458. [PubMed] [Google Scholar]
- Deguchi T., Yoshioka M. L-Arginine identified as an endogenous activator for soluble guanylate cyclase from neuroblastoma cells. J Biol Chem. 1982 Sep 10;257(17):10147–10151. [PubMed] [Google Scholar]
- Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
- Garthwaite J., Charles S. L., Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988 Nov 24;336(6197):385–388. doi: 10.1038/336385a0. [DOI] [PubMed] [Google Scholar]
- Garthwaite J., Garthwaite G., Palmer R. M., Moncada S. NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur J Pharmacol. 1989 Oct 17;172(4-5):413–416. doi: 10.1016/0922-4106(89)90023-0. [DOI] [PubMed] [Google Scholar]
- Hibbs J. B., Jr, Taintor R. R., Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987 Jan 23;235(4787):473–476. doi: 10.1126/science.2432665. [DOI] [PubMed] [Google Scholar]
- Hibbs J. B., Jr, Vavrin Z., Taintor R. R. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol. 1987 Jan 15;138(2):550–565. [PubMed] [Google Scholar]
- Knowles R. G., Palacios M., Palmer R. M., Moncada S. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5159–5162. doi: 10.1073/pnas.86.13.5159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwon N. S., Nathan C. F., Stuehr D. J. Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. J Biol Chem. 1989 Dec 5;264(34):20496–20501. [PubMed] [Google Scholar]
- Lepoivre M., Boudbid H., Petit J. F. Antiproliferative activity of gamma-interferon combined with lipopolysaccharide on murine adenocarcinoma: dependence on an L-arginine metabolism with production of nitrite and citrulline. Cancer Res. 1989 Apr 15;49(8):1970–1976. [PubMed] [Google Scholar]
- Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
- McCall T. B., Boughton-Smith N. K., Palmer R. M., Whittle B. J., Moncada S. Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J. 1989 Jul 1;261(1):293–296. doi: 10.1042/bj2610293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989 Jun 1;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. [DOI] [PubMed] [Google Scholar]
- Palacios M., Knowles R. G., Palmer R. M., Moncada S. Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochem Biophys Res Commun. 1989 Dec 15;165(2):802–809. doi: 10.1016/s0006-291x(89)80037-3. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jan 16;158(1):348–352. doi: 10.1016/s0006-291x(89)80219-0. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
- Patthy A., Bajusz S., Patthy L. Preparation and characterization of Ng-mono-, di- and trimethylated arginines. Acta Biochim Biophys Acad Sci Hung. 1977;12(3):191–196. [PubMed] [Google Scholar]
- Rémésey C., Demigné C., Aufrère J. Inter-organ relationships between glucose, lactate and amino acids in rats fed on high-carbohydrate or high-protein diets. Biochem J. 1978 Feb 15;170(2):321–329. doi: 10.1042/bj1700321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salvemini D., de Nucci G., Gryglewski R. J., Vane J. R. Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6328–6332. doi: 10.1073/pnas.86.16.6328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scannell J. P., Ax H. A., Pruess D. L., Williams T., Demny T. C. Antimetabolites produced by microorganisms. VI. L-N 5 -(1-iminoethyl) ornithine. J Antibiot (Tokyo) 1972 Mar;25(3):179–184. doi: 10.7164/antibiotics.25.179. [DOI] [PubMed] [Google Scholar]
- Stuehr D. J., Kwon N. S., Gross S. S., Thiel B. A., Levi R., Nathan C. F. Synthesis of nitrogen oxides from L-arginine by macrophage cytosol: requirement for inducible and constitutive components. Biochem Biophys Res Commun. 1989 Jun 15;161(2):420–426. doi: 10.1016/0006-291x(89)92615-6. [DOI] [PubMed] [Google Scholar]
- Tayeh M. A., Marletta M. A. Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. J Biol Chem. 1989 Nov 25;264(33):19654–19658. [PubMed] [Google Scholar]
- Wright C. D., Mülsch A., Busse R., Osswald H. Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun. 1989 Apr 28;160(2):813–819. doi: 10.1016/0006-291x(89)92506-0. [DOI] [PubMed] [Google Scholar]