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toxic products such as isoprostanes and reactive aldehydes @iserich, Patel et al. 1998). Lipid
peroxidation is a characteristic feature of nearly all inflammatory diseases (Kuhn, Belkner et
al. 1994; Quinlan, Lamb et al. 1996; Kuhn, Heydeck et al. 1997; Li, Maher et al. 1997).
On the other hand, NO can also serve as a protective factor. There are also lipid derived
radicals both free and membrane bound which contribute to inflammatory conditions by
inducing membrane damage again resulting in alteration of fluidity and integrity, as well as
the production of eicosanoids and eicosonoid-like isomers which possess potent bioactivity.
Direct reaction of NO with radical lipids results in inhibition of lipid oxidation and in this way
may prevent lipid oxidation induced tissue damage (Rubbo, Radi et al. 1994; Gutierrez,
Nieves et al. 1996; Wink, Cook et al. 1996; ODonnell, Chumley et al. 1997).
3.3.6 Reactions with genes
Transcriptional regulation of several genes by NO have been reported. Interestingly, these are
in general anti-inflammatory (Naruse, Shimizu et al. 1994; Pilz, Suhasini et al. 1995);
examples include regulation of adhesion molecules, the haem metabolising enzyme,
haemoxygenase (Foresti, Clark et al.1997) and glutathione synthesis (Moellering, McAndrew
et al. 1998).
3.3.7 Making sense of the reactions
In essence, the reactions that are important in biological systems depend on the amount of NO
and where the NO is formed. The short half life and reactivity means NO is likely to act as a
local messenger molecule, transferring messages within and between individual cells. In
biological systems, when small amounts are formed as a mediator for physiological processes,
the NO preferentially binds to haem, hence in the blood stream most NO is quickly bound to
haemoglobin. From here it rapidly decomposes to yield predominantly nitrate (NOl-) and
some nitrite (NOz') and the compounds are eliminated in the urine with a half life of five to
eight hours. NO will also interact with other heme containing proteins such as enz).mes
particularly sGC which results in a rapid increase in activity and production of cGMP. Excess
NO is mopped up by other nitrosation reactions, for example nitrosothiols and these are now
known to be active in their own right, and a way of stabilising NO in a bioactive form and
potentially facilitating NO transport in tissue.
When released in much larger amounts, it is likely that NO more often reacts with other
elements such as metals, for example copper, iron and zinc proteins releasing free Cu*, Fe*
and Zn** and generating Oz and highly toxic hydroxyl radicals leading to effect massive
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