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3.1<br />

Chapter 3: <strong>The</strong> synthesis, reactivity and control <strong>of</strong> nitric oxide<br />

Introduction<br />

<strong>The</strong> previous chapter detailed the two areas where nitrogen compounds were being<br />

increasingly recognised for their importance; air pollution and biological systems. In air<br />

pollution the nitrogen oxides were associated with excess mortality, in particular respiratory<br />

and cardiovascular morbidity; and in the biological systems, NO was found to be a<br />

widespread fundamental messenger. In this chapter, I will detail how NO is produced and<br />

cover its highly reactive and interactive properties. I will discuss the nitric oxide synthase<br />

(NOS) enzymes and how they are controlled in the physiological roles and the host defence<br />

roles <strong>of</strong> NO. <strong>The</strong> properties <strong>of</strong> NO needed to be understood when preparing to design<br />

experiments to measure it in vivo.<br />

3.2 Properties <strong>of</strong> nitric oxide<br />

Figure 3.1: <strong>The</strong> molecular structure <strong>of</strong> NO<br />

ao OO<br />

oN=O..<br />

NO is a clear, colourless gas. It is a free radical with an unpaired electron (. N=O, abbreviated<br />

NO, see Figure 3.1) and therefore it is highly reactive with a half life <strong>of</strong> seconds and readily<br />

combines with other free radicals (Beckman and Crow 1993). However it does not self react,<br />

possibly because its bond length is intermediate between double and triple bond lengths<br />

(Braker and Mossman 1975). Its small size and the fact that it is a relatively non-polar<br />

molecule means that it moves readily through hydrophobic lipid membranes (Shaw and<br />

Vosper 1977 Malinski, Taha et al. 1993; Liu, Miller et al. 1998). Its reactivity means that it<br />

binds quickly with transition metals such as iron, copper, cobalt, or manganese that are central<br />

ions to many cytochromes and oxidases, and in the case <strong>of</strong> iron, haemoglobulin. NO can be an<br />

oxidant or a reducing agent depending on the 'redox' environment. NO is soluble in water up<br />

to 2 millimoles per litre at 200C in one atmosphere, but has a high partition coefficient so it<br />

usually exists as a gas. NO reacts rapidly with oxygen in air producing nitrogen dioxide (NOz)<br />

(Vallance and Collier 1994). NO is very soluble in lipid and water and is therefore fully<br />

diffusible in the environment <strong>of</strong> the cell (Archer 1993; Henry, Lepoivre et al. 1993).<br />

70

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