Nitric isoform

Three isoforms of NO synthesizing enzymes ( nitric oxide synthase (NOS)) were isolated, purified, and cloned neuronal NO synthase ( neuronal nitric oxide synthase (nNOS) or isoform (I), immunological or inducible NOS ( inducible (immunological) nitric oxide synthase (iNOS) or isoform (II), and endothelial NOS ( endothelial nitric oxide synthase (eNOS) or isoform... 

NO synthases (NOS, L-arginine, NADPH oxygen oxi-doreductases, nitric oxide forming EC 1.14.13.39) represent a family of enzymes that catalyze the formation of nitric oxide (NO) from the amino acid L-arginine. In mammals, three isoforms of NOS have been identified. They are termed neuronal NOS (nNOS, NOS I, NOS1), inducible NOS (iNOS, NOS H, NOS2), and endothelial... 

F13. Forstermann, U and Kleinert, H., Nitric oxide synthase Expression and expressional control of the three isoforms. Arch. Pharmacol. 3S2,351-364 (1995). 

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... 

Sakata K, Hirose Y, Qiao Z, Tanaka T and Mori H. 2003. Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett 199(2)439-145. 

Because NO synthases belong to the same superfamily of enzymes as cytochrome P-450, they are able to produce not only nitric oxide (although it is undoubtedly their main function) but also other free radicals, first of all, superoxide. In 1992, Pou et al. [148] showed that brain nitric oxide synthase (NOS I) produced superoxide identified as a DMPO—OOH adduct in a calcium- or calmodulin-dependent manner. This finding was confirmed in numerous studies for all three isoforms of NO synthase. Although the structures of all the three NO oxidase... 

The constituent of paint, 2-nitropropane, exhibiting genotoxicity and hepatocarcinogeni-city was oxidized by liver microsomes forming nitric oxide, which was identified as a ferrous NO complex [61]. Clement et al. [62] concluded that superoxide may participate in the microsomal oxidation of /Y-hydroxyguanidincs, which produced nitric oxide, urea, and the cyanamide derivative. Caro et al. [63] suggested that the oxidation of ketoxime acetoxime to nitric oxide by microsomes enriched with P-450 isoforms might be mediated by hydroxyl or hydroxyl-like radicals. 

The formation of nitric oxide in microsomes results in the inhibition of microsomal reductase activity. It has been found that the inhibitory effect of nitric oxide mainly depend on the interaction with cytochrome P-450. NO reversibly reacts with P-450 isoforms to form the P-450-NO complex, but at the same time it irreversibly inactivates the cytochrome P-450 via the modification of its thiol residues [64]. Incubation of microsomes with nitric oxide causes the inhibition of 20-HETE formation from arachidonic acid [65], the generation of reactive oxygen species [66], and the release of catalytically active iron from ferritin [67],... 

Funae, Y., Okada, S., Isoforms of cytochrome P-450 on organic nitrate-derived nitric oxide release in human heart vessels. FEBS Lett. 452 (1999), p. 165-169... 

S. K., Weber, P. C., Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation, Nat. Struct. Biol. 6 (1999), p. 233-242... 

Southan, G. J., Szabo, C.. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms, Biochem. Pharmacol. 51 (1996),... 

C., Amidines are potent inhibitors of nitric oxide synthases preferential inhibition of the inducible isoform, Eur. J. Pharmacol. 291 (1995), p.311-318... 

A series of analogues of 2-iminopiperidine have been prepared and have been shown to be potent inhibitors of the human nitric oxide synthase isoforms °. The cyclopentanone oxime 346 was esterified with sodium hydroxide and benzenesulfonyl chloride and the subsequent Beckmann rearrangement afforded the 6-propylvalerolactam 348 as the major product and 3-propylvalerolactam 347 as a minor product (equation 133). The major product was converted into the intended 2-iminopiperidine 349. 

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