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Mechanisms and Biomarkers (WG 4) page 13
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Antioxidant systems in aerobic organisms can be divided into those involving protein whose
amount and function is regulated genetically and those directly provided by nutrients from
foods. Obviously, interactions exits between these antioxidants and combinations may lead to
considerably increase the efficiency when compared to a single antioxidant.
Enzymatic antioxidant proteins
Among the antioxidant proteins, three main enzymes form the primary line of defence
against the reactive oxygen species i.e. superoxide anion and hydrogen peroxide.
Superoxide dismutase was the first enzyme investigated by Fridovich (1986). This enzyme
dismutates the super oxide anion into hydrogen peroxide at rates 10 000 times higher than
spontaneous dismutation. It represents the major intracellular antioxidant enzyme in aerobic
cells. SOD in the cytoplasm differs by the presence of Cu and Zn in the catalytic site from the
one found in the mitochondria characterised by the presence of manganese (Mn) (Fridovich,
1989). Superoxide dismutase exerts antioxidant protection by avoiding the reaction of
superoxide anion with biomolecules and also by inhibiting the formation of the cytotoxic
peroxynitrite (Radi et al., 1991a).
Glutathione peroxidase is a selenium-containing enzyme which decomposes hydrogen
peroxide to water by reducing equivalents amounts of glutathione (GSH) (Jones et al., 1981).
It can also decomposes other peroxides such as lipid hydroperoxydes. The renewal of GSH
pool is made by glutathione reductase which reduces GSSG (the oxidised form of GSH) to
GSH using NADPH as co-factor. These reactions occurred in the cytoplasm and cytoplasmic
GSH/GSSG ration is an indicator of oxidative stress (Trible and Jones, 1990).
Catalase is a heme containing protein which also decomposes hydrogen peroxide into water
and molecular oxygen (Thayer, 1986). Catalase is mainly present in the peroxisomes of
nucleated cells and it has been recently detected in heart mitochondria where it is involved in
the defence against hydrogen peroxide produced at high levels in the heart mitochondria as
compared with other organs (Radi et al., 1991b). The heart catalase becomes effective when
the H2O2 concentration rises above that which can be effectively cleared by glutathione
peroxidase.
Non-enzymatic antioxidant proteins
As a secondary protection, one must consider the proteins involved in the degradation
of oxidised biological molecules (nucleases, lipases and proteases) as well in the repairing
mechanisms, particularly those involved in DNA (Demple and Harrison, 1994) and protein