ANTIOXIDANTS
In their definition of the term, Halliwell & Gutteridge (1989) state that an antioxidant is 'any
substance that, when present at low concentrations compared with that of an oxidizable
substrate, significantly delays or inhibits oxidation of that substrate'. This definition includes
compounds of a non-enzymatic as well as an enzymatic nature. Clearly, the diversity of antioxidants
matches that of pro-oxidants. The principles underlying the antioxidant functions
have been discussed (Sies, 1993).
Prevention
A first line of defense against reactive oxygen species is, of course, protection against their
formation, i.e. prevention. There are numerous strategies in biology designed to evade oxidative
stress, ranging from the plankton that descends from the surface of the seawater to lower levels
of solar irradation, to the packaging of DNA in chromatin to shield the genetic material by
providing alternative targets. Microbes have developed specialized strategies to prevent oxygendependent
killing by phagocytes.
Regarding radical formation, first it should be mentioned that some of the enzymes prone to
generate free radical species are ingeniously designed. Cytochrome oxidase, which carries out
most of the cellular oxygen reduction, does not release superoxide or other radicals, even though
it contains iron and copper ions. Likewise, the three-dimensional structure of the enzyme
ribonucleotide reductase keeps the radical character of the tyrosyl function in subunit B from
spreading to the environment by forming an appropriate 'cage'.
Furthermore, the prevention of initiation of chain reactions includes the binding of metal
ions, in particular iron and copper ions. Metal chelation is a major means of controlling lipid
peroxidation and DNA fragmentation. Thus, the metal-binding proteins ferritin, transferrin,
coeruloplasmin and others, e.g. metallothionein, are of central importance in the control of