Free Radicals, Types, Sources and Damaging Reactions
Submitted by Dr. Tamer Fouad, M.D.
Free radicals are a chemical species that possess an unpaired electron in the outer shell of the molecule.
Damaging reactions of free radicals
Oxidative stress is defined as the state in which the level of toxic reactive oxygen intermediates (ROI) overcomes the endogenous antioxidant defences of the host (Bulger EM, Helton WS; 1998). This state results in an excess of free radicals, which can react with cellular lipids, proteins, and nucleic acids, leading to local injury and eventual organ dysfunction. Lipids are probably the most susceptible biomolecule to free radical attack.
Cell membranes are a rich resource of PUFA, which are readily attacked by oxidising agents; a process that is called lipid peroxidation. This is particularly damaging because it is a self-perpetuating process (Cheeseman KH, 1993). The breakdown of lipid hydroperoxides often involves transition metal ion catalysis.
LH + R?? L?+ RH
L? + O2? LOO?
LOO? + L'H ? LOOH + L'?
LOOH ? LO?, LOO?, aldehydes.
Proteins & nucleic acids seem to be less susceptible than PUFAs to free radicals, in that there seems to be less possibility in the formation of rapidly progressing chain reactions. Random attack of radicals on proteins is unlikely unless extensive. This happens only if radicals are allowed to accumulate (which is not likely in normal cells), or if the damage is focussed on a particular site of the protein. One way that the damage is focused is if the protein binds a transition metal ion (Marx G, Chevion M; 1986 and Stadtman ER, Oliver CN; 1991).
Oxidising radicals readily attack DNA if they are formed in its vicinity as has been clearly the case demonstrated by radiation biologists. It is therefore a vulnerable & important target. As with proteins there seems little possibility that the damage may spread into a chain reaction. Again for damage to occur it must either be site specific (leading to strand breaks) or it must elude the repair systems before replication occurs leading to mutations (Cheesman and Slater, 1993).
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