The biochemistry of NO

Because NO is a radical, we expect it to be reactive. Its half-life is estimated at approximately 1-5 s, so it needs to be synthesized often in the cell. As we saw in Case study 10.1, there is a biochemical price to be paid for the reactivity of biological radicals. Like Oj, NO participates in some reactions that are not beneficial to the cell. Indeed, the radicals O2 and NO combine to form the peroxynitrite ion (5)  

The peroxynitrite ion is a reactive oxygen species that damages proteins, DNA, and hpids, possibly leading to heart disease, amyotrophic lateral sclerosis (Lou Gehrig s disease), Alzheimer s disease, and multiple sclerosis. We note that the structure of the ion is consistent with the bonding scheme of Fig. 10.35 because the unpaired electron in NO is slightly more localized on the N atom, we expect that atom to form a bond with an O atom from the O2 ion. 

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Many biochemical reactions depend on the presence of metal ions. These ions may be present in specific coordination complexes or may act to facilitate or inhibit reactions in solution. In the first part of this chapter, we describe a few of these compounds and reactions, together with the biochemistry of NO, which has many functions that have only recently been discovered. 

Only three kinds of octopus have been confirmed to be biolu-minescent Japetella, Eledonella, and Stauroteuthis syrtensis (Johnsen et al., 1999). No information is available concerning the biochemistry of their luminescence. 

A convenient preparative method for conjugated nitroalkenes has been developed based on the reaction of nitrogen oxides. Nitric oxide (NO) is commercially available and used in the industry for the mass production of nitric acid. Nitric oxide is currently one of the most studied molecules in the fields of biochemistry, medicine, and environmental science.47 Thus, the reaction of NO with alkenes under aerobic conditions is of a renewed importance.48... 

NO donors have been used for more than a century in the treatment of cardiovascular diseases. Clearly, the NO/cGMP system plays a major role in platelet inhibition in vivo and in vitro, however, the complex regulation of cGM P levels, as well as the crosstalk to the cAMP system, makes it a signaling network that is not yet fully understood. The contribution of cGMP-independent mechanisms in NO signaling in platelets is far from clear. Careful use of the crucial genetically altered mouse models, the variety of NO donors with clear differences in biochemistry and functional platelet effects as well as the many so-called specific activatory or inhibitory research tools will certainly help to elucidate the still unknown areas of NO signaling in platelets in the near future. 

The biomedical research on nitrogen oxides has nearly exclusively involved NO and its oxidative metabolites. Reduced species, such as nitroxyl (HNO) and hydroxylamine (NH2OH), have been largely unexplored in mammalian systems until recently. The initial interest in the biochemistry of HNO arose following observation of nitrous oxide (N20) during bacterial reduction of nitrite to NH3. Dehydrative dimerization of HNO to form N20 (77, 78) was well documented in the gas phase,... 

As is to be expected, the literature on the biochemistry of the phospha-tidylinositols in cellular reactions has been immense. No attempt will be made to cover this topic. Instead, only the salient features of the biochemical behavior of these compounds will be summarized in a concluding segment of this discussion. References to particularly informative review articles will be cited at that time. The main theme here, as in previous sections, will be devoted to the chemical characteristics and characterization of these most interesting phosphoglycerides. 

Nitric oxide is an unstable gas and, if exposed to the air, it quickly oxidizes to nitrogen dioxide, NO2 (a brown gas). This helps it to overcome its odd electron unstable structure. However, in the closed environment of the body, this process does not occur and so the NO carries out its unique roles within the body s cells. Its production is probably a result of oxidation of amino acids or proteins. Nitric oxide has been implicated in the biochemistry of virtually every mammalian organ system, including inflammatory and degenerative diseases. It is present in the blood and other parts of the body and there are very small quantities in the brain. These concentrations are so small that it is only in recent years that it has been discovered following the development of sensitive analytical instruments. 

Despite our understanding of the biochemistry of niacin, we still cannot account for the characteristic photosensitive dermatitis in terms of the known metabolic lesions. There is no apparent relationship between reduced availability of tryptophan and niacin, and sensitivity of the skin to ultraviolet (UV) light. The only biochemical abnormalities that have been reported in the skin of pellagrins involve increased catabolism of the amino acid histidine leading to a reduction in the concentration of urocanic acid, a histidine metabolite that is the major UV-absorbing compound in normal dermis (see Figure 10.6). 

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