Bővebb ismertető
FOREWORD
Although the story of oxygen begins with the discoveries of the English theologian Joseph Priestley and the Swedish pharmacist Carl Wilhelm Scheele, the concept of oxygen as a gas was not established until Johan Baptiste van Helmont (1577—1644) outlined the existence of various types of air. The first connection between air and oxygen appears to have been made by John Mayow (1641 —1679), a student of Robert Hooke who published two treatises on respiration — Tractatus duo and Tractatus quinque. He deduced that inhaled air is necessary for life and that it throws off something which passes into the blood through the lungs. Even though the element was a victim of mistaken criteria and of false concepts, in particular the phlogiston theory of Georg Ernst Stahl, various other oxygen products were discovered. In 1818, Louis-Jacob Thenard described a method for preparing hydrogen peroxide, and in 1840 C. F. Schonbeim discovered ozone.
The first experiments indicating that oxygen could have detrimental effects were carried out by Paul Bert in 1878. However, our current understanding of oxygen toxicity is based on the theoretical considerations of Michaelis (1946) and the experimental considerations of Gerschman et al. (1954). These observations led to concepts concerning oxygen free radical involvement in toxicity. It was through the work carried out by Irwin Fridovich that the univalent reduction product of oxygen — the superoxide radical — came to the foreground of biochemistry, based initially on his work with Phillip Handler on the mechanism of xanthine oxidase. Fridovich and collaborators later discovered a class of metalloenzymes — the superoxide dismutases — which dismutate superoxide radicals to hydrogen peroxide and oxygen.
As a result of the discovery of superoxide dismutase, Fridovich proposed the superoxide theory of oxygen toxicity. Whether superoxide radicals are sufficiently reactive to be considered toxic has been a matter of some debate (and polemics), particularly from physical chemists. On the basis of the low reactivity of this radical, it has been suggested that superoxide dismutase may have some other as yet unknown function in vivo and that the dismutation of superoxide radicals is a spurious function. There is ample evidence demonstrating the production of superoxide radicals in biological systems. What is wrong in having an enzyme to dismute superoxide radicals? in theory it need not be a toxic free radical species to require an enzyme to dismute it? Skeptics will never be convinced. Everyone who has carried out any scientific investigation is aware of the prejudices that arise. These should be avoided so that purely objective results can be obtained.
Oxygen radical damage has been implicated in various inflammatory disorders, as well as in mutagenicity and carcinogenicity. The identity of the oxygen species which is responsible for these effects is unclear. The hydroxyl radical, because of its high reactivity, has been implicated as the main source of oxygen radical damage. The formation of this radical is believed to take place through a metal-catalyzed Haber-Weiss reaction. A major question remains as to what is the physiologic metal catalyst of this reaction? Another oxygen species — singlet oxygen — has also been considered to be involved in oxygen toxicity. The involvement of singlet oxygen in biochemistry is due to the work of C. Foote and A. U. Khan. However, its formation and reactivity in biological systems has not been clearly demonstrated.
Oxygen in one form or another is clearly toxic. This does not mean that no natural defenses have been built against it. Besides superoxide dismutase, other enzymes, such as catalase and glutathione peroxidases, have evolved to prevent oxidative damage. The study of oxygen in biological systems is therefore a multidisciplinary field. It not only concerns the production of oxygen-centered free radicals and the damage they cause, but also the natural defense mechanism. It is clear that this handbook encompasses the whole spectrum of oxygen radical research. The various sections of the book should provide useful experimental procedures to all those who want to put new ideas to test. Bob Greenwald is to be congratulated for
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