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تسجيل

Disorders of Glutathione Metabolism

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P727-728

2026-07-19

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As depicted in Fig. 1 (reaction 6), the reduced form of glutathione (GSH) serves to protect the neutrophil from the harmful effects of hydrogen peroxide on NADPH oxidase and other neutrophil proteins. Adequate intracellular levels of GSH are maintained by recycling oxidized glutathione (GSSG) to GSH by glutathione reductase (see Fig. 1, reaction 7), as well as by de novo synthesis of glutathione by glutathione synthetase (see Fig. 1., reaction 9). Severe deficiencies in either of these enzymes are extremely rare and are apparently inherited in an AR manner.3 In the case of glutathione reductase deficiency, the respiratory burst terminates prematurely, presumably owing to the toxic effects of accumulating hydrogen peroxide on NADPH oxidase. However, this brief burst of O2⁻ appears to be sufficient for adequate microbial killing because the few patients reported have not had problems with recurrent infections. However, they do have con genital hemolytic anemia during periods of oxidant stress caused by diminished levels of glutathione reductase in erythrocytes. In glutathione synthetase deficiency, the respiratory burst proceeds normally. Patients have severe metabolic acidosis caused by elevated levels of 5-oxoproline, which is the product of the first step in glutathione syn thesis and is present in increased levels because of a lack of feedback of GSH on the synthetic pathway. Patients with glutathione synthetase deficiency also have intermittent neutropenia (perhaps caused by the acidosis), as well as oxidant-induced hemolysis. There are mild problems with recurrent infections. Therapy with vitamin E (400 IU/day) has been found to be beneficial in patients with severe glutathione synthetase deficiency with hemolysis and infections.

Fig1. REACTIONS OF RESPIRATORY BURST PATHWAY. GSH, Glutathione; GSSG, oxidized glutathione; HOCl, hypochlorous acid; NADPH, nicotinamide adenine dinucleotide phosphate.