Genetic deficiencies of glucose-6-phosphate dehydrogenase (G6PD) and NADPH predispose affected erythrocytes to destruction from peroxides. Conversely, genetic deficiencies of catalase do not predispose affected erythrocytes to peroxide-induced destruction. These observations have served to strengthen the assumption that the NADPH/glutathione/glutathione peroxidase pathway is the principal means for disposal of H2O2 in human erythrocytes. Recently, however, mammalian catalase was found to have tightly bound NADPH and to require NADPH for the prevention and reversal of inactivation by its toxic substrate (H2O2). Since both catalase and the glutathione pathway are dependent on NADPH for function, this finding raises the possibility that both mechanisms destroy H2O2 in human erythrocytes. A comparison of normal and acatalasemic erythrocytes in the present study indicated that catalase accounts for more than half of the destruction of H2O2 when H2O2 is generated at a rate comparable to that which leads to hemolysis in G6PD- deficient erythrocytes.
The catalase within normal, intact human erythrocytes was completely inactivated with amino triazole. The rate of 14CO2 evolution, when the cells were subsequently incubated with 14C-labeled glucose, provided a measure of the rate at which NADPH was being oxidized by the glutathione peroxidase/reductase system for the disposal of H2O2. This rate was determined in control cells and in catalase-inactivated cells while the cells were exposed to H2O2, which was generated at various constant and predetermined rates by glucose oxidase. The results indicated that catalase handles approximately half of the generated H2O2. The glutathione peroxidase/reductase mechanism accounted for the other half. These results are in agreement with our earlier findings on erythrocytes of a subject with a genetic deficiency of catalase. However, an unexpected result with the present approach was the finding that the increased dependence on the glutathione peroxidase/reductase mechanism did not occur until greater than 98% of the catalase had been inactivated. The latter observation indicates that catalase and the glutathione peroxidase/reductase system function intracellularly in a manner very different from that previously ascribed to them. An explanation of the findings requires that the two methods of H2O2 disposal function in a coordinated way, such as a sequential action in which the glutathione peroxidase/reductase system is the rate-limiting step.
Serum LDH levels have been found to be significantly increased in non- Hodgkin lymphoma (NHL) patients, both histiocytic and lymphocytic. The duration of survival of NHL negatively correlates with the level of serum lactic dehydrogenase (LDH), and statistical analysis reveals that patients with lower levels of LDH have a longer survival rate than the patients with higher LDH activity, irrespective of their histologic classification. The analysis of the results by the Test for Trend in Prognosis allows us to establish that the correlation of the rate of survival and LDH levels is independent from other clinical parameters.
Serum LDH levels have been found to be significantly increased in non- Hodgkin lymphoma (NHL) patients, both histiocytic and lymphocytic. The duration of survival of NHL negatively correlates with the level of serum lactic dehydrogenase (LDH), and statistical analysis reveals that patients with lower levels of LDH have a longer survival rate than the patients with higher LDH activity, irrespective of their histologic classification. The analysis of the results by the Test for Trend in Prognosis allows us to establish that the correlation of the rate of survival and LDH levels is independent from other clinical parameters.
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