Nitric Oxide Synthase NOS

The nitric oxide synthases are single polypeptides that encode a haeme domain, a calmodulin- 

Eight cDNA sequences have been reported deriving from three known NOS genes in human, cow, rat and mouse (Nathan and Xie 1994). 

The inhibitory effect of aluminium on in vitro tetrahydrobiopterin synthesis in brain preparations may be due to competition with the magnesium re- 

In the rat anterior pituitary gland, nitric oxide synthase is present in gonadotrophs and in foUiculo-stellate cells (Ceccatelli et al. 1993). Castration and ovariectomy, respectively, resulted in markedly increased nitric oxide synthase mRNA levels. In the male rat a small, but not significant, increase was seen 12 h after surgery, whereas at 3 h levels were still similar to sham-operated rats. After 24 h there was a 3-fold increase in mRNA levels, and this remained elevated for 14 days, the longest period studied. Also in the female rats, there was a clear but less strong increase at 4 and 14 d after ovariectomy. Substitution treatment with testosterone or estrogen completely prevented these increases in male and female rats, respectively. 

In a model of idiopathic pneumonia syndrome after bone marrow transplantation, iNOS deletional mutant mice (-/-) given donor bone marrow and spleen T cells (BMS) exhibited improved survival compared with matched BMS controls (Yang et al. 2001). Bronchoalveolar lavage fluids obtained on day 7 post bone marrow transplantation from iNOS(-/-) BMS mice contained less tumour necrosis factor-a and interferon-y, indicating that NO 

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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 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... 

The last phase of the excitotoxic cascade involves the activation of various biochemical pathways, among which phospholipases, proteases (in particular cal-pain), kinases and calmodulin-regulated enzymes such as nitric oxide synthase (NOS) play a prominent role. 

The existence of nitric oxide synthase (NOS) in phagocytes (see below) provides a different kind of stimulation and the inhibition of NADPH oxidase. It has been found [72] that the low physiological concentrations of peroxynitrite formed from NO and superoxide stimulated superoxide production by PMA-activated human PMNs through the ERK MAPK pathway, while higher peroxynitrite concentrations inhibited it. Moreover, NADPH oxidase was inhibited by lidocaine, a sodium-blocker, in OZ-activated neutrophils through the suppression of p47phox translocation [73]. 

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 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). 

M. A., Progress in the development of selective nitric oxide synthase (NOS) inhibitors, Curr. Pharm. Des. 8 (2002), p.177-200... 

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). 

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. 

As discussed in Chapter 22, the activity of gnanyl cyclase is regulated by the messenger nitric oxide this gas stimulates the activity of this enzyme. Nitric oxide is generated from arginine catalysed by the enzyme nitric oxide synthase (NOS) (Figure 19.16). 

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