Neuronal nitric oxide synthase enzyme

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... 

ALS because SODl encodes for an antioxidant enzyme. Although the relevance of oxidative stress is not fully understood, it is believed that mutations in SODl promote a structural change that allows a higher rate of interaction between the substrates and the active site of the enzyme, resulting in increased production of free radical species. However, there are not sufficient experimental data supporting this hypothesis because if SODl mutants cause peroxynitrite-dependent cell death in vitro, it would be expected that reduction in the levels of peroxynitrite by inhibition of neuronal nitric oxide synthase (nNOS) would improve the motor neuron outcomes. However, these experiments did not show a decrease in motor neuron damage (Facchinetti et ah, 1999 Upton-Rice et ah, 1999 Son et ah, 2001). 

Knight, K. and N.S. Scrutton (2002). Stopped-flow kinetic studies of electron transfer in the reductase domain of neuronal nitric oxide synthase Reevaluation of the kinetic mechanism reveals new enzyme intermediates and variation with cytochrome P450 reductase. Biochem. J. 367,19-30. 

In a different approach, hybrids of P540 BM3 and neuronal nitric oxide synthase (nNOS) were generated in which the heme and reductase domains of the respective enzymes were swapped, while maintaining the natural domain order [112, 209]. Such hybrids could successfully be expressed in E. coli and were shown to be catalytically active [162, 209], With snch hybrids,... 

Figure 1 Models for analyzing tissue PO2 disappearance rates measured with PO2 microelectrodes after stopping perfusate flow to the carotid body, (a) Inhibitory effects of NO on a single enzyme model for C3tiochrome oxidase (high-affinity pathway) are shown, based on a decrease in maximum tissue PO2 disappearance rate (top panel) and increase in (middle panel) with NO. Predicted 02-dependent PO2 disappearance rates (bottom panel) for NO concentrations of 0 (circle), 100 (triangle). 250 (diamond), and 500 nM (square) are shown, (b) The single-oxidase model was modified by adding a second, low-affinity (high enzyme (top panel) for 02-dependent production of NO by neuronal nitric oxide synthase (nNOS). Predicted 02-dependent PO2 disappearance rates (bottom panel) are shown with the additional amount of O2 consumed by the low-affinity pathway (dashed lines) over that required by the high-affinity pathway (solid lines) for each NO concentration (symbols same as above).

Nitric oxide (NO) has also been implicated in certain maternal behaviors, including the timing of parturition in rats and olfactory memory formation in lactating sheep (Gammie and Nelson, 1999), as well as aggression and maternal aggression. Nitric oxide is produced from L-arginine by three different tissue-localized nitric oxide synthase (NOS) enzymes neuronal (nNOS), en-... 

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. 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

The CNS contains a substantial amount of nitric oxide synthase (NOS), which is found within certain classes of neurons. This neuronal NOS is an enzyme activated by calcium-calmodulin, and activation of NMDA receptors, which increases intracellular calcium, results in the generation of nitric oxide. Although a physiologic role for nitric oxide has been clearly established for vascular smooth muscle, its role in synaptic transmission and synaptic plasticity remains controversial. Perhaps the strongest case for a role of nitric oxide in neuronal signaling in the CNS is for long-term depression of synaptic transmission in the cerebellum. 

In vivo NO" is generated from the essential amino acid L-arginine by a family of enzymes called nitric oxide synthases (NOS) [1], Three isoforms have been described and cloned - endothelial NOS (eNOS), brain or neuronal NOS (nNOS), and inducible macrophage-type NOS (iNOS). All isoforms of NOS make the same products, NO and L-citrulline, by incorporating an O-atom of dioxygen into L-arginine. Only the amount of NO, the conditions under which it is made, and the location where it is synthesized differ among the three isoforms. 

The gaseous free radical nitric oxide (NO), a non-conventional neural messenger, is synthesized in neurons by the enzyme nitric oxide synthase (NOS), which can be revealed in histological sections by NADPH-diaphorase histochemistry or NOS immunohisto-chemistry. The role of NO in neural signaling has raised considerable interest (see, for example, Schmidt and Walter, 1994), stemming also from the finding that NOS has a discrete distribution in subsets of brain neurons, including intense expression in neuronal subsets of the striatum (Vincent, 2000). 

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