Volume 10, number 1 MOLECULAR & CELLULAR BIOCHEMISTRY January 31,1976 E N Z Y M E D E F E N S E A G A I N S T R E A C T I V E E R Y T H R O C Y T E S A N D T U M O R CELLS Argante BOZZI*, Irene Roberto STROM*, Anna Giuseppe ROTILIO* (Received April 1, 1975) O X Y G E N D E R I V A T I V E S . II. MAVELLI*, Alessandro FINAZZI A G R 0 * , Maria WOLF*, Bruno MONDOVI?, and Summary Introduction The enzymatic destruction of oxidizing products produced during metabolic reduction of oxygen in the cell (such as singlet oxygen, H202 and OH radical) involves the concerted action of superoxide dismutase-which removes 02 and yields HeO2-and H202 removing enzymes such as catalase and glutathione peroxidase. A differ- ence in distribution or ratio of these enzymes in various tissues may result in a different reactiv- ity of oxygen radicals. It was found that in red blood cells superox- ide dismutase and catalase are extracted in the same fraction as hemoglobin, while glutathione peroxidase appears to be "loosely" bound to the cellular structure. This suggests that in red blood cells catalase acts in series with superox- ide dismutase against bursts of oxygen radicals formed from oxyhemoglobin, while glutathione & peroxidase may protect the cell membrane against low concentrations of H202. On the other hand, catalase activity is absent in various types of ascites tumor cells, while glutathione peroxidase and superoxide dismut- ase are found in the cytoplasm. However, the peroxidase/dismutase ratio is lower than in liver cells, and this may provide an explanation for the higher susceptibility of tumor cells to treat- ments likely to involve oxygen radicals. * Institute of Biological Chemistry and C.N.R. Centre for Molecular Biology, University of Rome, Rome, Italy. t Institute of Applied Biochemistry, University of Rome, Rome, Italy. It is now well established that in aerobic cells many biochemical events may lead to the production of superoxide anion radicals (02) through the univalent reduction of 02, and that this species yields further derivatives which are supposed to be the primary source of oxidative damage in the cell 1. A likely pattern of reaction is the following2:02 dismutates giving H202 and the highly reactive singlet oxygen: further reaction between 02 and H202 gives the strongly oxidizing OH radicals. Recently the problem of scavenging the reac- tive oxygen derivatives from the cellular milieu has received much attention. The discovery of a new enzymatic activity displayed by a long known protein, i.e. the superoxide dismutase activity of erythrocuprein 3, has been followed by a considerable amount of research about its physiological role 410. It has been proposed that the enzymic dismutation of 02 into H202 and 02 by superoxide dismutase as well as that of H202 into H20 and 02 by catalase prevents the formation of the highly oxidizing singlet ox- ygen 6'7'1°''1 and also the possible reaction of 02 with hydrogen peroxide yielding OH radicals 2'7. It is also well known that H202 is destroyed by glutathione peroxidase in cells or cell compart- ments lacking catalase 12. It appears from these considerations that distribution and levels of superoxide dismutase and H2Oz-removing enzymes determine the steady state concentration in the cell of all the oxidative species (singlet oxygen, H:O2, OH) Dr. W. Junk b.v. Publishers - The Hague, The Netherlands 11