PEROXIDES 695 



Effects on Metabolism 



Hydrogen peroxide inhibits brain respiration and especially the oxidation 

 of succinate (Dickens, 1946 a). If one compares the effects on various tis- 

 sues, the sensitivity to hydrogen peroxide depends on the relative concentra- 

 tions of catalase; the more catalase, the less inhibition. In brain, 75 roM hy- 

 drogen peroxide inhibits respiration 36% and succinate oxidation 95% over 

 a 60 min period. It was thought initially that the toxic effects of high 

 oxygen tension on brain might be due to hydrogen peroxide released, but 

 this was shown not to be true. 



If Lactobacillus is grown anaerobically, the cells lose their iron enzymes 

 and catalase; if they are then exposed to oxygen, hydrogen peroxide is form- 

 ed and the cells are killed (Warburg et al., 1957). Since cancer cells possess 

 an anaerobic type of metabolism and contain much less catalase than nor- 

 mal cells, it was postulated that this may be the cause of the greater sensi- 

 tivity of cancer cells to hydrogen peroxide. It was found that 1 mM hy- 

 drogen peroxide has no effect on the aerobic or anaerobic glycolysis of em- 

 bryo tissue, but inhibits both almost completely in ascites cells. Since the 

 catalactic activity of embryo tissue is around 10-fold that of the ascites 

 cells, this could explain the differential susceptibility. Inasmuch as radia- 

 tion of cells can induce hydrogen peroxide formation, this may be one reason 

 for the more selective effects of radiation on cancer cells. Holzer and Frank 

 (1958) extended these observations in ascites cells to show that hydrogen 

 peroxide at 0.056 mM not only inhibits glycolysis 86%, but simultaneously 

 reduces the NAD concentration very markedly (0.31 to 0.05 //moles/ml). 

 Triose-P and fructose-diP rise, indicating a block of the phosphoglyceral- 

 dehyde dehydrogenase. However, they found the extracted enzyme to be 

 inhibited only 37% by 0.079 mM hydrogen peroxide, so that concentra- 

 tions effectively blocking glycolysis would have little effect on this enzyme 

 (assuming the same sensitivities of the intact and extracted enzymes). They 

 thus postulated that the inhibition is due to a reduction of NAD and that 

 this suppresses the oxidation of triose-P. Nicotinamide can protect both 

 NAD and glycolysis from hydrogen peroxide, and Pantlitschko and Seelich 

 (1960) showed that it could overcome the inhibition when added 1 hr after 

 the hydrogen peroxide. Baker and Wilson (1963) confirmed the inhibition 

 of anaerobic glycolysis in Ehrlich ascites carcinoma ceUs, although the ef- 

 fects were not as marked as observed previously — some inhibition at 0.3 

 mM, around 50% at 0.9 mM, and 80% at 2 mM — and further showed 

 that during the oxidation of unsaturated fatty acids some hydrogen per- 

 oxide is formed and may depress glycolysis. Piitter (1961) studied the 

 possible relationship between glycolysis and transplantability of ascites 

 cells, but encountered the difficulty that the hydrogen peroxide used to 

 inhibit glycolysis is fairly rapidly decomposed so that the inhibition dis- 

 appears. Thus it requires above 1 mM to interfere with transplantability. 



