Influence of aging on rat liver enzymes involved in glutathione synthesis and degradation.

The purpose of this study was to determine the effects of aging on the activities of rat liver enzymes involved in the synthesis and degradation of glutathione, as well as those important for maintaining glutathione in its reduced form. gamma-Glutamylcysteine synthetase, gamma-glutamyltransferase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities were measured in liver fractions prepared from male and female Fischer-344 rats at the ages 4, 14, and 29 months. The activity of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, and overall rates of glutathione synthesis were unaffected by aging. In contrast, the activity of gamma-glutamyltransferase, the key enzyme in glutathione degradation, was markedly influenced by animal age; activity increased with age in male rats and decreased with age in female rats. Age-associated alterations also were observed in activities of hepatic enzymes needed to maintain glutathione in its reduced form. Glutathione reductase activity was greater in old female rats and glucose-6-phosphate dehydrogenase activity was greater in old male rats than in young and middle-aged rats of the same sex. Age-dependent changes in glutathione metabolizing enzymes could have important toxicological implications.