Endothelial nitric-oxygen synthase

Abu-Saud, H.M., Ichimori, K., Presta, A., and Stuehr, DJ. (2000) Electron transfer, oxygen binding, and nitric oxide feedback inhibition in endothelial nitric oxide synthase, J. Biol. Chem. 275, 17349-17357. 

Endothelial nitric oxide synthase (eNOS). The enzyme responsible for nitric oxide production in human endothelium. Nitric oxide (NO) is a gas that relaxes vascular smooth muscle cells, induces vasodilatation and is critical for global vascular homeostasis. cNOS is a homodimer enzyme that couples oxygen consumption to L-arginine use to produce NO. In its uncoupled form, cNOS is rendered into a source of superoxides instead of NO. 

Loke, K.E., McConnell, P.I., Tuzman, J.M., Shesely, E.G., Smith, C.J., Stackpole, C.J., Thompson, C.I., Kaley, G., Wolin, M.S., and Hintze, T.H. (1999). Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption. 

Berka, V., Yeh, H.C., Gao, D., Kiran, R, and Tsai, A.L. (2004). Redox function of tetrahydro-biopterin and effect of L-arginine on oxygen binding in endothelial nitric oxide synthase. Biochemistry 45(41), 13137-13148. 

Endothelial nitric oxide synthase regulates vascular tone and inhibits platelet aggregation and leukocyte adhesion. Suda et al. demonstrated that intravenous adenovims-mediated endothelial nitric oxide synthase gene transfer improved lung graft oxygenation and reduced neutrophilic sequestration (85). 

BH4 = Tetrahydrobiopterin CAM = Cytotoxic activated macrophage cNOS = Constitutive nitric oxide synthase CPR = Cytochrome P450 reductase EDRF = Endothelial-derived relaxation factor EPR = Electron paramagnetic resonance spectroscopy IL-1 = Interleukin-1 iNOS = Inducible nitric oxide synthase EPS = Lipopolysaccharide, or endotoxin NMMA = ISp-monomethyl-L-arginine NOS = Nitric oxide synthase ROS = Reactive oxygen species SOD = Superoxide dismutase TNF = Tumor necrosis factor. 

Nitric oxide ( NO) also contributes to the alveolar epithelium s oxidant burden, primarily as a result of the formation of reactive oxygen or nitrogen species. NO, one of the smallest and most distinctive biological mediators, is generated by nitric oxide synthase (NOS) which has three isoforms neuronal (nNOS, isoform I), inducible (iNOS, isoform II) and endothelial (eNOS, isoform III). nNOS and eNOS are constitutively expressed in cells and generate NO in small quantities for brief periods of time in response to increased intracellular CA2+ concentrations. It is currently unclear whether the level of expression or the enzymatic activity or either eNOS or nNOS is modulated by pathogens or inflammatory stimuli. 

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. 

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... 

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