XENOBIOTIC-METABOLIZING ENZYMES OF THE KIDNEY

The kidney possesses most of the common xenobiotic metabolizing enzyme s, and is thus able to make an important contribution to the body's me tabolism of drugs and foreign compounds. An overview of the renal loca lization, catalytic activity, developmental regulation, induction, and sex and species differences for the key enzymes involved in phase I a nd phase II of xenobiotic metabolism is presented. In general, the cat alytic activities of the various renal enzymes are lower than those of the liver, although there are exceptions, such as the enzymes involve d in the processing of glutathione conjugates to their mercapturic aci ds. Xenobiotic metabolizing enzymes are not evenly distributed along t he nephron; cytochromes P-450 and those enzymes involved in the conjug ation of glutathione, glucuronic acid, or sulfate are primarily locali zed in the proximal tubules. However, some isozymes of cytochrome(s) P -450 and glutathione S-transferases are selectively localized in cells of the thick ascending limb and distal tubules, whereas prostaglandin H synthase is concentrated in the collecting ducts in the medulla. Th us, the proximal tubule, the principal site of xenobiotic biotransform ation, is particularly susceptible to chemical insult, and the localiz ation of prostaglandin synthase in the inner medulla and papilla may b e a contributary factor to the toxicity produced by chemicals in this part of the nephron. Many of the enzymes discussed, in addition to met abolizing foreign compounds, have important endogenous functions in th e kidney, such as the regulation of salt and water balance and the syn thesis of vitamin D.