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Arginine

About: Arginine is a(n) research topic. Over the lifetime, 16677 publication(s) have been published within this topic receiving 579791 citation(s). The topic is also known as: L-Arg & (2S)-2-amino-5-guanidinopentanoic acid.
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Journal ArticleDOI
TL;DR: The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes.
Abstract: The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes. Nitric oxide is synthesized from the amino acid L-arginine by a family of enzymes, the nitric oxide synthases, through a hitherto unrecognized metabolic route -- namely, the L-arginine-nitric oxide pathway1–8. The synthesis of nitric oxide by vascular endothelium is responsible for the vasodilator tone that is essential for the regulation of blood pressure. In the central nervous system nitric oxide is a neurotransmitter that underpins several functions, including the formation of memory. . . .

6,319 citations


Journal ArticleDOI
16 Jun 1988-Nature
TL;DR: It is demonstrated that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture and the strict substrate specificity of this reaction suggests that L- arginine is the precursor for NO synthesis in vascular endothelium cells.
Abstract: Nitric oxide (NO) released by vascular endothelial cells accounts for the relaxation of strips of vascular tissue1 and for the inhibition of platelet aggregation2 and platelet adhesion3 attributed to endothelium-derived relaxing factor4. We now demonstrate that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture. Nitric oxide was detected by bioassay5, chemiluminescence1 or by mass spectrometry. Release of NO from the endothelial cells induced by bradykinin and the calcium ionophore A23187 was reversibly enhanced by infusions of L-arginine and L-citrulline, but not D-arginine or other close structural analogues. Mass spectrometry studies using 15N-labelled L-arginine indicated that this enhancement was due to the formation of NO from the terminal guanidino nitrogen atom(s) of L-arginine. The strict substrate specificity of this reaction suggests that L-arginine is the precursor for NO synthesis in vascular endothelial cells.

4,732 citations


Journal ArticleDOI
David S. Bredt1, Solomon H. SnyderInstitutions (1)
TL;DR: It is shown that nitric oxide synthetase activity requires calmodulin, and the native enzyme appears to be a monomer.
Abstract: Nitric oxide mediates vascular relaxing effects of endothelial cells, cytotoxic actions of macrophages and neutrophils, and influences of excitatory amino acids on cerebellar cyclic GMP. Its enzymatic formation from arginine by a soluble enzyme associated with stoichiometric production of citrulline requires NADPH and Ca2+. We show that nitric oxide synthetase activity requires calmodulin. Utilizing a 2',5'-ADP affinity column eluted with NADPH, we have purified nitric oxide synthetase 6000-fold to homogeneity from rat cerebellum. The purified enzyme migrates as a single 150-kDa band on SDS/PAGE, and the native enzyme appears to be a monomer.

3,175 citations


01 Jan 2016
Abstract: Nitric oxide mediates vascular relaxing effects of endothelial cells, cytotoxic actions of macrophages and neu- trophils, and influences of excitatory amino acids on cerebellar cyclic GMP. Its enzymatic formation from arginine by a soluble enzyme associated with stoichiometric production of citruline requires NADPH and Ca2 . We show that nitric oxide synthetase activity requires calmodulin. Utilizing a 2',5'-ADP affmity col- umn eluted with NADPH, we have purified nitric oxide synthetase 6000-fold to homogeneity from rat cerebellum. The purified enzyme migrates as a single 150-kDa band on SDS/PAGE, and the native enzyme appears to be a monomer. Endothelium-derived relaxing factor, a labile substance formed by endothelial cells, which mediates vasodilation, has been shown to be identical to nitric oxide (NO) (1-3). In addition to relaxing blood vessels, NO has multiple messen- ger functions as it has been demonstrated in macrophages (4) and in brain tissue (5-7). NO appears responsible for the cytotoxic effects of macrophages and neutrophils (8). We have obtained direct evidence for NO as a messenger for the influences of the excitatory amino acid glutamate on cGMP in the cerebellum (7). We showed a striking enhancement by glutamate and other excitatory amino acids of the conversion of arginine to NO and the associated formation of citrulline. Moreover we observed that Nw-monomethyl-L-arginine (MeArg), an inhibitor of the enzymatic conversion of arginine to NO, inhibits glutamate-elicited cGMP formation, an influ- ence selectively reversed by excess arginine. Evidence that NO mediates functions of tissues as diverse as the brain, endothelium, and blood cells suggests a wide- spread role for NO as a messenger molecule. Localizing NO formation at a cellular level throughout the body would be greatly facilitated by immunohistochemical identification of NO synthetase, the NO-forming enzyme. The mechanism of conversion of arginine to NO, presently unclear (9), would be greatly clarified by purification of NO synthetase. Charac- terization of this enzyme has been hampered by the complex assays required to assay the enzyme by monitoring NO formation directly. We have shown that NO formation is accompanied by the stoichiometric conversion of arginine to citrulline, permitting a simple, sensitive, and specific enzyme assay measuring the transformation of (3H)arginine to (3H)citrulline (7). Utilizing this assay in the present study, we have purified NO synthetase to homogeneity. We demon- strate that NO synthetase is a calmodulin-requiring enzyme, explaining numerous reports of a crucial role for calcium in endothelium-dependent smooth muscle relaxation.

3,082 citations


Journal ArticleDOI
Guoyao Wu1, Sidney M. Morris2Institutions (2)
TL;DR: Physiological roles and relationships between the pathways of arginine synthesis and catabolism in vivo are complex and difficult to analyse, owing to compartmentalized expression of various enzymes at both organ and subcellular levels.
Abstract: Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified complex patterns of interaction among these enzymes. There is growing interest in the potential roles of the arginase isoenzymes as regulators of the synthesis of nitric oxide, polyamines, proline and glutamate. Physiological roles and relationships between the pathways of arginine synthesis and catabolism in v i v o are complex and difficult to analyse, owing to compartmentalized expression of various enzymes at both organ (e.g. liver, small intestine and kidney) and subcellular (cytosol and mitochondria) levels, as well as to changes in expression during development and in response to diet, hormones and cytokines. The ongoing development of new cell lines and animal models using cDNA clones and genes for key arginine metabolic enzymes will provide new approaches more clearly elucidating the physiological roles of these enzymes. Correspondence may be addressed to either Dr. G. Wu (e-mail g-wu@tamu.edu) or Dr. S. M. Morris, Jr. (e-mail sid@hoffman.mgen.pitt.edu) at the addresses given.

2,378 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20225
2021347
2020381
2019332
2018357
2017379