Hepatic glutathione (GSH) concentration was significantly higher in rats and mice compared to either fathead minnows or rainbow trout. In rodents, the concentration of GSH approximated the Km of hepatic glutathione peroxidase (GPx), whereas in fish GSH concentration was less than the Km of GPx. The significantly lower Km for oxidized glutathione (GSSG) of glutathione reductase compared to the Km for GSH of the peroxidase is consistent with the large ratio of reduced‐to‐oxidized glutathione in all four species. The concentration of GSH in rodent liver far exceeds the Km for hepatic glutathione‐S‐transferase (GST), which contrasts with that observed for fish. Furthermore, the greater activity of renal gamma‐glutamyl transpeptidase in rodents compared to fish suggests that, once formed, glutathione conjugates are rapidly hydrolyzed, leading to greater mer‐capturic acid production in rats and mice. Collectively, these data suggest that rodents are quite capable of conducting GSH‐dependent detoxification of prooxidants and electrophiles, whereas in fish GSH‐dependent metabolism appears to be self‐limited by the availability of endogenous GSH. Accordingly, the data suggest that fish may be disproportionately more susceptible than rodents to xenobiotics that are eliminated principally by GSH‐dependent metabolic detoxification.
- Enzyme kinetics