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3.3 Reactions of nitric oxide
The reaction of NO at any given time is dependent on a number of factors; the rate of reaction
and therefore the concentrations of the species with which NO reacts the fastest, the
concentration of NO, the reduction-oxidation (redox) environment in which it is found and
therefore the presence and concentration of Oz, the availability of other interacting
compounds and the pH (see Table 3.2). As well as local reactions, it is now believed that the
interaction between NO and thiols and amines may be a way of stabilising NO in a bioactive
form, potentially facilitating NO transport in tissue (Gaston, Drazen et al. 1994). I will review
the different pathways briefly below.
3.3.1 Reactive nitrogen species and superoxide reactions
High levels of NO exposure can cause significant damage. It can damage all classes of
macromolecules including DNA. It can destroy mitochondrial enzymes, prevent DNA
synthesis, and inhibit protein synthesis (Hibbs, Taintor et al. 1988; Curran, Ferrari et al. l99l;
Kwon, Stuehr et al. 1991; Stadler, Billiar et al. 1991; Lancaster 1992; Irpoivre, Flaman et al.
r9e2).
However it has become increasingly obvious that reactions with NO in the presence of Oz
forming NO derived reactive nitrogen species are equally important in mediating toxic injury.
These compounds include nitrite (Noz-), nitrate (No:-), No2, nitrous acid (HNoz) or
dinitrogen trioxide (NzOa). It also interacts with Oz to produce superoxides such as
perioxynitrite (ONOO-) and peroxynitrous acid (ONOOH), both strong oxidising agents.
These can continue to react with all classes of biomolecules including lipids, DNA, thiols,
amino acids and metals leading to the two mechanisms of damage which are oxidation and
nitration @iserich, Patel et al. 1998).
NOz is produced by the reaction of NO with Oz and oxidation of NOz to NOr. 6,
myeloperoxidase (Ignarro, Fukuto et al. 1993). This reaction will therefore occur in areas of
high macrophage numbers and high 02 concentration and therefore is commonly seen in the
Iung. The exposure of human plasma to NOz causes rapid loss of ascorbate, uric acid, c-
tocopherol, bilirubin, and protein thiols as well as increasing lipid peroxidation (Halliwell, Hu
et al. 1992). Exposure of lung lining to NOz leads to loss of ascorbic acid, uric acid. and
glutathione (Postlethwait, Langford et al. 1995: Kelly and Terley lggT). Under acidic
conditions NO2 becomes protonated to form HNO2. At least two biological compartments
experience pH low enough to allow HNO2 formation in vivo; the stomach with a pH 2.5-4.5
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