Trends in Biochemical Sciences
ForumThe rise of ROS
Section snippets
O2 reduction
The reduction of O2 to 2H2O requires four electrons. If this were to occur by transfer of pairs of electrons, only H2O2 would be of concern. However, O2 has a preference for univalent pathways of reduction, resulting in intermediate reactive oxygen species (ROS) (Fig. 1), such as the superoxide radical (O2−) and hydroxyl radical (OH). The latter can also be generated by the interaction of O2− and H2O2 in the presence of metal ions. Both O2− and OH are extremely reactive and can cause molecular
Reactive oxygen: an historical synopsis
During the past two decades, research in the area of free radicals and oxidative stress has exploded. The intensity of research in this area is evident in the huge number of papers published and the frequent coverage of the subject in the popular press. The number of publications indexed under ‘reactive oxygen species (ROS)’ has doubled every six years since the 1960s.
This sphere of scientific research goes back to the 1930s when Michaelis proposed that all biological oxidations proceed as
Defenses against reactive oxygen
To minimize the damaging effects of ROS, aerobic organisms evolved both non-enzymatic and enzymatic antioxidant defenses. Non-enzymatic defenses include such compounds as vitamins C and E, and β-carotene. Plants also produce a large variety of small non-enzymatic antioxidant compounds as second-tier defenses, such as glutathione, ascorbate, tocopherols, flavonoids, alkaloids, and carotenoids capable of quenching ROS.
Enzymatic defenses include superoxide dismutases, catalases and peroxidases.
My initial interests and involvement
Catalase activity has been found in all plants examined. Conventional wisdom held that, as in animals, one form of the enzyme was present and performed functions similar to its animal counterpart. However, these assumptions were challenged by a rather simple experiment I did in 1963, which demonstrated the existence of multiple forms of catalase in one organism.
I was influenced by the pioneering work of Clem Markert, who was later to become my colleague and close friend. In a landmark paper,
ROS serve essential and useful functions
ROS normally exist in all aerobic cells in balance with biochemical antioxidants. Oxidative stress occurs when this critical balance is disrupted because of excess ROS, antioxidant depletion, or both. To counteract the oxidant effects and to restore redox balance, cells must reset important homeostatic parameters. Changes associated with oxidative damage and with restoration of homeostasis frequently lead to activation or silencing of genes encoding regulatory transcription factors, antioxidant
Concluding remarks
The oxygen paradox is indeed the paradox of evolution itself. Evolutionary pressures have made the best of a bad situation by generating mechanisms to curtail the toxic effects of ROS, an unavoidable consequence of the aerobic lifestyle, and to put them to constructive uses. Indeed evolution has co-opted ROS to serve necessary and useful purposes in the maintenance of cellular homeostasis and in the communication of cells with the external environment. The view of ROS as villains that
In retrospect
It has been a unique privilege for me to have worked on oxidative stress and antioxidant defense genes for most of my scientific career, and to observe the field develop from a matter of arcane interest for a few to a major subject for many, in the forefront of modern biomedical and agricultural sciences. The advice I received early in my scientific training from my late friend and mentor Milislav Demerec at the Cold Spring Harbor Laboratory, to ask a biologically relevant question and to
Acknowledgements
I gratefully acknowledge the generous, and continuous, support of my work over many years by the US Department of Energy, National Institute of Health, National Science Foundation, Department of Agriculture, and Environmental Protection Agency.
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