Homogenates of perfused rat brain generated oxidized glutathione from reduced glutathione during incubation with dopamine or serotonin. This activity was blocked by pargyline, a monoamine oxidase inhibitor, or by catalase, a scavenger of hydrogen peroxide. These results demonstrate formation of hydrogen peroxide by monoamine oxidase and the coupling of the peroxide to glutathione peroxidase activity. Oxidized glutathione was measured fluorometrically via the oxidation of NADPH by glutathione reductase. In the absence of added dopamine or serotonin, a much smaller amount of reduced glutathione was oxidized; this activity was blocked by catalase, but not by pargyline. Therefore, endogenous production of hydrogen peroxide, not linked to monoamine oxidase activity, was present. These results indicate that glutathione peroxidase (linked to hexose monophosphate shunt activity) can function to eliminate hydrogen peroxide generated by monoamine oxidase and other endogenous sources in aminergic neurons.
Interpretation of biochemical measurements in the human brain after death is complicated by a variety of premortem, perimortem, and postmortem factors. The activity of glutamic acid decarboxylase (GAD) in particular has been found to vary considerably among human brains. In contrast to neurotransmitter-associated enzymes, metabolic enzymes are present in all brain cells and should not be specifically lost by patterned neuronal cell loss such as that which occurs in Parkinson disease. We compared the activity of GAD to that of the metabolic enzymes creatine kinase (CK), adenylate kinase, hexokinase, beta-glucuronidase, and malate, lactate, glucose-6-phosphate, and isocitrate dehydrogenases in 24 regions of six human brains. Of the metabolic enzymes, only CK showed a 5-fold variation approaching that of GAD. Like GAD, CK activity was stable postmortem, but its activity was apparently inversely related to the severity and duration of the preterminal illness. CK may be a useful marker of agonal deterioration.
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