Diminished blood levels of reduced glutathione and alpha-tocopherol in twotriosephosphate isomerase-deficient brothers

The glutathione redox system and alpha-tocopherol, both of which are essent ial for maintaining the normal structure of biological membranes, some othe r lipid-soluble antioxidants (lycopene, beta-carotene, retinol), and lipid peroxidation, were investigated in the blood from two triosephosphate isome rase (TPI)-deficient brothers. Both of the genetically identical compound h eterozygote brothers have congenital hemolytic anemia, but only one of them has a neurological defect, the second cardinal symptom of TPI deficiency. Whole blood reduced glutathione levels were markedly decreased in both brot hers. The glutathione reductase activities as well as the NADPH contents of their erythrocytes were in the normal range or slightly enhanced. Increase d ratio of oxidized/reduced glutathione, elevated glutathione S-transferase activity, and increased d-lactate level, a metabolite of the glyoxalase pa thway, were detected only in the neurologically affected propositus. The pl asma carotenoids (lycopene + beta-carotene), alpha-tocopherol/cholesterol triglyceride ratios, and the erythrocyte alpha-tocopherol levels were sign ificantly decreased in both patients. It seems conceivable that membrane al terations due to the low level of these reducing agents may contribute to t he shortened life span of erythrocytes. The imbalance of the prooxidant/ant ioxidant homeostasis as well as the increased rate of methylglyoxal formati on may also have been involved in the development of the neurological manif estations in the propositus. (C) 2000 Academic Press.