Nitric-oxide synthase function

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Testosterone also plays a significant albeit complex role in erectile function. Testosterone is responsible for much of a man s libido. With low serum concentrations, libido declines. Additionally, testosterone helps with stabilization of intracavernosal levels of nitric oxide synthase, the enzyme responsible for triggering the nitric oxide cascade. Interestingly, some patients with low or borderline low serum concentrations of testosterone will have normal erectile function, while some with normal levels will have dysfunction. 

H24. Hinder, F Booke, M Traber, L. D., Matsumoto, N., Nishida, K Rogers, S and Traber, D. L., Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide. Crit. Care Med. 24,131 -136 (1996). 

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... 

Chen LY, Mehta P, Mehta JL (1996) Oxidized LDL decreases L-arginine uptake and nitric oxide synthase protein expression in human platelets relevance of the effect of oxidized LDL on platelet function. Circulation 93 1740-1746... 

Exposure to trichothecenes at levels that partially inhibit translation upregulates expression of many inflammatory and immune-related genes including macrophage, Thl and Th2 cytokines as well as chemokines, cyclooxygenase 2 and inducible nitric oxide synthase.1518 Contrastingly, suppressive effects of trichothecenes on leukocyte function are intimately linked with the induction of apoptosis as has been demonstrated in macrophages, T cells and B cells both in vivo and in vitro.19-20... 

Stuehr, D. J., Structure-function aspects in the nitric oxide synthases, Annu. Rev. Pharmacol. Toxicol. 37 (1997), p. 339-359... 

Ghosh, D. K., Salerno, J. C., Nitric oxide synthases domain structure and alignment in enzyme function and control. Front. Biosci. 8 (2003),... 

Raman, C. S., Li, H., Martasek, P., Kral, V., Masters, B. S., Poulos, T. L., Crystal structure of constitutive endothelial nitric oxide synthase a paradigm for pterin function involving a novel metal center, Cell 95 (1998),... 

Giovanelli, J., Campos, K. L., Kaufman, S., Tetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine, Proc. Natl. Acad. Sci. USA 88 (1991), p. 7091-7095... 

Effect of a nitric oxide synthase inhibitor, S-ethylisothiourea, on cultured cells and cardiovascular functions of normal and lipopolysaccharide-treated rabbits, J. Biochem. (Tokyo) 119 (1996), p. 553-558... 

Besides cholesterol efflux from arterial wall and its role in RCT, additional properties of HDL have been proposed for its protective anti-atherogenic activities. HDL protects vascular function by a number of potential alternative mechanisms, including inhibition of LDL oxidation [8,9], platelet aggregation and coagulation [10], and endothelial monocyte adhesion [11], as well as promotion of endothelial nitric oxide synthase (eNOS) [12], and prostacyclin synthesis [13-15]. The proposed alternate protective mechanisms for HDL are attractive but many of them lack validation under in vivo conditions. 

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