Nitric oxide synthase , arginine

See also Glutamate as a Precursor of Other Amino Acids, Nitric Oxide Synthase, Arginine, Citrulline, Guanylate Cyclase... 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

Vazquez, J., Lydic, R. Baghdoyan, H. A. (2002). The nitric oxide synthase inhibitor NG-Nitro-L-arginine increases basal forebrain acetylcholine release during sleep and wakefulness. J. Neurosci. 22, 5597-605. 

The Ca2+-calmodulin complex may also activate nitric oxide synthase (NOS), which binds to a PDZ domain of PSD-95. Activated NOS produces NO from arginine NO, in turn, activates guanylate cyclase, the enzyme that catalyzes the conversion of GTP to the intracellular messenger cGMP, which activates protein kinase G (PKG). 

Chen LY, Mehta P, Mehta JL (1996) Oxidized LDL decreases L-arginine uptake and nitric oxide synthase protein expression in human platelets relevance of the effect of oxidized LDL on platelet function. Circulation 93 1740-1746... 

Endogenous NO is produced almost exclusively by L-arginine catabolism to L-citrul-line in a reaction catalyzed by a family of nitric oxide synthases (NOSs) [3]. In the first step, Arg is hydroxylated to an enzyme-bound intermediate "-hydroxy-1.-arginine (NHA), and 1 mol of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and O2 are consumed. In the second step, N H A is oxidized to citrulline and NO, with consumption of 0.5 mol of NADPH and 1 mol of 02 (Scheme 1.1). Oxygen activation in both steps is carried out by the enzyme-bound heme, which derives electrons from NADPH. Mammalian NOS consists of an N-terminal oxy-... 

Scheme 7.13 Nitric oxide synthase-mediated conversion of N-hydroxy-L-arginine to nitric oxide.

Giovanelli, J., Campos, K. L., Kaufman, S., Tetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine, Proc. Natl. Acad. Sci. USA 88 (1991), p. 7091-7095... 

J. M., Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage by L-arginine analogs, Arch. Biochem. Biophys. 315 (1994), p. 213-218... 

Conformationally-restricted arginine analogues as alternative substrates and inhibitors of nitric oxide synthases, Bioorg. Med. Chem. 7 (1999), p. 1097-1104... 

Babu, B. R., Frey, C., Griffith, O. W., L-Arginine binding to nitric-oxide synthase. The role of H-bonds to the nonreactive guanidinium nitrogens, J. Biol. Chem. 274 (1999),... 

Rogers, N. E., Ignarro, L. J., Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine, Biochem. Biophys. Res. Commun. 189 (1992), p. 242—249... 

Nitric oxide is widely distributed and at least three isoenzymes of nitric oxide synthase (NOS) have been described iNOS (inducible), eNOS (endothelial) and nNOS (neuronal). The substrate for NOS is the amino acid arginine ... 

As shown in Figure 5.5, nitric oxide is synthesized from the amino acid arginine under the influence of nitric oxide synthase (NOS). This enzyme exists in several tissues as either a constitutive or inducible protein (iNOS). 

K. I. Hosoya, Y. Horibe, K. J. Kim, and V. H. Lee. Carrier-mediated transport of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, in the pigmented rabbit conjunctiva. J Pharmacol Exp Ther 285 223-227 (1998)... 

Reiativeiy recentiy, the gases nitric oxide (NO) and carbon monoxide (CO) have been found to act as neurotransmitters in the nervous system. Nitric oxide is synthesized from L-arginine via nitric oxide synthase, requiring NADPH as a co-enzyme and tetrahydrobiopterin as a cofactor. Unlike other neurotransmitters, NO is a smaii, very soiubie moiecuie and cannot be stored in synaptic vesicles. Rather, it is synthesized on demand and freeiy diffuses through membranes. It is not broken down enzymaticaiiy because it is unstabie and degrades rapidiy. NO may have several actions, one of which is to increase the production of cGMP by guanyiyi... 

Abbreviations BSO, D.L-buthionine-. i -sulfoxime L , lipid alkyl radicals LH, lipid LO, Upid alkoxyl radicals LOO, Upid peroxyl radicals L-NAME, yV -nitro-L-arginine-methyl ester MBl, methylene bridge index (mean number of h -aUytic methylene positions per fatty add) NO, nitric oxide NOS, nitric oxide synthase NO, nitrite N02, nitrogen dioxide NO2CI, nitryl chloride O2 , superoxide OH, hydroxyl radical OL, epoxyaUyhc radical OLOO, epoxyperoxyl radical 0=NOO , peroxynitrite SNAP, S-nitroso-iV-acetyl-D.L-penicillamine SOD, superoxide dismutase contd. onp. 98, Subcellular Biochemistry, Volume 36 Phospholipid Metabolism in Apoptosis. 

The role of arginase in some cells is not to produce urea but to regulate the concentration of arginine. This is important since arginine is the substrate for the reaction that produces an important messenger molecule, nitric oxide, via the enzyme nitric oxide synthase. 

Nitric oxide, which is produced from arginine in the reaction catalysed by nitric oxide synthase, reacts with O2 to produce the very toxic peroxynitrite free radical (Figure 17.27). 

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