ABSTRACT
This chapter discusses the various methods for modulating cellular glutathione levels. α-Tocopherol, ascorbic acid, and glutathione (l-y-glutamyl-l-cysteinylglycine; GSH) are several of the natural cellular antioxidants, with glutathione being present in the highest concentration. Glutathione is a cofactor for several enzymes, for example, glyoxylase, maleylacetoacetate isomerase, formaldehyde dehydrogenase, prostaglandin endoperoxidase isomerase. The degradation of glutathione, glutathione disulfide, and glutathione S-conjugates is catalyzed by the externally facing membrane bound γ-glutamyl transpeptidase, the only enzyme known to catalyze the hydrolysis of the γ-glutamyl bond. Several inborn deficiencies of enzymes involved in glutathione metabolism have been described, such glutathione disulfide reductase deficiency which is associated with increased susceptibility to erythrocyte hemolysis. Increasing cellular glutathione levels may be useful in the treatment of various diseases. Glutathione administration may be thought of as a method to deliver cysteine. Raising glutathione levels by use of cysteine prodrugs is limited because of the feedback inhibition by glutathione on the first enzyme, γ-glutamylcysteine synthetase.
