Nitric oxide isoenzymes

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 ... 

Boer R., Ulrich, W.-R., Klein, T., Mirau, B., Haas, S., Baur, I. The Inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes, Mol. Pharmacol. 2000, 58, 1026-1034. 

Nitric oxide and carbon monoxide. The gaseous molecules NO and CO have both been found in the brain, and neuronal NO synthase (nNOS or NOS I) has been studied intensively.844-847 NO synthases and the functions of NO and CO are discussed in Section A7 and in Chapter 18. Complexity in understanding the role of NO in the brain arises from the fact that different isoenzyme forms of NO synthase occur in three different types of cell nNOS in neurons, iNOS from microglial immune system cells, and eNOS from endothelial cells of capillary blood vessels.846 All three types of cells are so tightly intermingled in the brain that it is hard to interpret observed experimental... 

Recent studies have shown that nitric oxide stimulates the synthesis of inflammatory prostaglandins by activating cyclooxygenase isoenzyme II (COX-2). Thus, inhibition of the nitric oxide pathway may have a beneficial effect on inflammatory diseases, including joint diseases. Studies using inhibitors of NOS-2 have shown that nitric oxide is required for maintaining COX-2 gene expression. 

Jolitha AB, Subramanyam MV, Asha Devi S (2006) Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol 41(8) 753-763 Kruse M, Navarro D, Desjardins P, Butterworth RF (2004) Increased brain endothelial nitric oxide synthase expression in thiamine deficiency relationship to selective vulnerability. Neurochem Int45(l) 49-56... 

Nitric oxide synthase (NOS) isoenzymes generate NO a recent paper summarizes and... 

The enzyme nitric oxide synthase (NOS), that produces NO and citrullin from arginine, occurs as several isoenzymes (Knowles et al., 1989). Type I NOS is a constitutive, calcium and calmodulin-dependent enzyme, present in neurons and, possibly, in glia. Type II NOS is calcium-independent and can be induced in macrophages and glial cells by exposure to bacterial lipopolysaccharide (Galea et al., 1992 Murphy et al., 1993). Type III NOS is the endothelial iso-enzyme. NOS-I, II and III are produced by diflferent genes (Bredt et al., 1991 Lamas et al., 1992 Xie et al., 1992 Lowenstein et al., 1992 Lyons et al. 1992 Ogura et al., 1993). NOS displays NADPH-dependent diaphorase... 

ABSTRACT In mammals, nitric oxide (NO) is a reactive free radical involved in diverse physiological functions. NO and its redox-related forms NO+ and NO react with di(oxygen) and its derivatives, with metalloproteins and thiol-containing proteins. NO-mediated nitrosation of proteins represents an important cellular regulatory mechanism. Biosynthesis of NO is catalysed by nitric oxide synthase (NOS). Three isoenzymes representing distinct gene products have been identified the inducible NOS isoform, the constitutive neuronal and endothelial isoforms. Inducible and constitutive NOSs have the same structural features, but their activities differ in their dependence to calcium and the rate of NO produced. The principal NO-mediated functions in mammals are endothelium-dependent relaxation, neurotransmission and immune response. The role of NO in the antitumor immune response comprises both regulatory and effector functions at the intra- or inter-cellular level. The first function includes inhibition of lymphocyte proliferation or participation in different transduction pathways. The second fiinction includes pro- or anti-tumoral effects and NO-mediated cell toxicity or cell resistance to apoptosis. 

Ritonavir inhibits the cytochrome P450 isoenzyme CYP2D6, which is responsible for the demethylenation of ecstasy, so concurrent use leads to a sharp rise in ecstasy plasma levels. Poor liver function (due to alcoholism) may have been a contributory factor in one patient, and further CYP inhibition by nitric oxide (the metabolite of amyl nitrate) may have contributed to another case. An additional factor is that ecstasy may show non-linear pharmacokinetics. Metamfetamine is also metabolised by CYP2D6 and its levels would therefore similarly be raised by ritonavir. 

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