Nitric-oxide synthase conversion

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). 

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

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Figure 19.16 Role of nitric oxide synthase in control of penile erection. Nitric oxide synthase catalyses conversion of arginine to nitric oxide, which then acts to acb vate guanyl cyclase which results in an increase in the concentrab on of cyclic GMP. The latter relaxes smooth muscle in the arterioles that supply blood to the corpora cavernosa in the penis so that blood flow increases and erection results.

The synthesis of NO requires merely one step the conversion of L-arginine into NO and citrulline. This conversion is catalyzed by the nitric oxide synthase (NOS) enzyme. Three distinct isoforms of the NOS enzyme have been cloned Isoform I (nNOS chromosome 12) is a Ca -dependent neuronal form of the enzyme Isoform n (mNOS or iNOS chromosome 17) is a Ca +-independent macrophage inducible form of the enzyme found in microglia Isoform III (eNOS, chromosome 7) is a Ca +-dependent form found in the endothelial cells that line blood vessels. Since NO is an extremely important messenger substance, the NOS enzyme is exquisitely regulated by processes such as phosphorylation and hormonal control. 

In some instances the type of inhibition has been found to be isozyme specific. For example, inducibly expressed isozymes (iNOS) and constitutively expressed isozymes (cNOS) of nitric oxide synthase (NOS) all catalyze the conversion of L-arginine to L-citrulline and nitric oxide (Equation 17.34). 

The 5-imino-l,4-diazepane 76 was prepared from the known diazepinone 74, by initial N-protecting group interconversion to give 75 followed by a three-step amide to amidine conversion. The compound 76 was prepared in connection with studies on nitric oxide synthase inhibitors but it proved to be inactive as an inhibitor of this enzyme <04BMCL5907>. 

The complex conversion of arginine to citrulline and nitric oxide is shown in Figure 21.3. The enzyme catalyzing the reaction is nitric oxide synthase. 

Mittal, C. K. (1993). Nitric oxide synthase Involvement of oxygen radicals in conversion of L-arginine to nitric oxide. Biochem. Biophys. Res. Commun. 193, 126-132. 

Figure 14.3 Enzymatic (nitric oxide synthase, NOS) conversion of L-arginine to citrulline resulting in nitric oxide (NO) release.

Nitric oxide (NO) has a key role in many bioregulatory systems, including immune stimulation, platelet inhibition, neurotransmission, and relaxation of smooth muscle [1]. Its biosynthesis derives from nitric oxide synthases which catalyse the conversion of L-arginine to L-citrulline, resulting in NO release. Among the proposed NO storage components are protein-bound thionitrosyls and protein-bound dinitrosyl iron complexes (DNIC) [2,3]. The latter are derived from iron-sulphur... 

NO- is a product of the conversion by nitric oxide synthase (NOS) of 1-arginine to 1-citruUine (Fig. 17.1). Three different classes of NOS can be found in the liver, the neuronal isoform (nNOS), present in the peribiliary plexus, the calcium-dependent endothelial (eNOS) in endothelial cells, and the calcium-independent... 

The main relaxing factor produced by the endothelium is nitric oxide or NO. After the first report by Furchgott and Zawadzki in 1980 that described an endothehum-derived relaxing factor (EDRF), it took 7 years to identify the EDRF as NO [19, 27, 28]. NO is a labile gas produced by the conversion of L-arginine to L citruUine by NO synthases, a group of heme-containing dimeric enzymes. Among the three isoforms, one is induced by several pro-inflammatory cytokines... 

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