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Mechanisms and Biomarkers (WG 4) page 8
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important intermediate for the oxidation-reduction reactions in intermediary metabolism, such
as the catabolism of xanthine to uric acid by flavoprotein oxidase. However, under normal
conditions, the main site of oxygen metabolism is the mitochondria where most of molecular
oxygen is consumed in the respiratory chain (Chance et al., 1979). Oxygen is reduced to water
by addition of four electrons, catalysed by the components of the respiratory chain. During
these reactions, 1 to 2 percent of oxygen not consumed are liberated as superoxide anion
(monovalent reduction) or hydrogen peroxide (divalent reduction). Other sites where reactive
metabolites of oxygen can be liberated are the liver and the immune cells. The potential
contribution of these sources of reactive oxygen often occurs during conditions such as
detoxication of xenobiotics during their metabolism in the liver or during inflammatory
processes often underlying pathological situations (Ames et al., 1993; Cannon and Blumberg,
1994). During these processes oxidases with the cofactors [(NAD(P)-H] use oxygen either to
metabolise the foreign toxic compounds into less toxic ones, a reaction which results in the
production of superoxide anion, or to destroy foreign organisms (bacteria, viruses) with
superoxide anion but also with other reactive oxygen species. Through these processes, many
compounds are formed, and those with unpaired electrons can be highly reactive free radicals.
Free radicals and reactive oxygen and nitrogen species
A free radical is any molecule containing one or more unpaired electrons and able to have an
independent existence (Halliwell, 1994). Thus superoxide anion is one example of an oxygen
centred free radical. Others have been identified centred on carbon (CCl3°) or on sulphur (R-
S°, thiyl radical) and in some cases the unpaired electron may be delocalized between 2 atoms
such as nitric oxide (NO°) or ascorbyl radical. The reactivity of free radicals is due to their
stabilisation by capture of another electron (from non radical or radical species). This leads to
2 consequences: first the life-time of free radicals are very short (10 -9 to