Xenobiotic metabolizing enzymes of the kidney

ABSTRACT-The kidney possesses most of the common xenobiotic metabolizing enzymes, and is thus able to make an important contribution to the body's metabolism of drugs and foreign compounds. An overview of the renal localization, catalytic activity, developmental regulation, induction, and sex and species differences for the key enzymes involved in phase I and phase I1 of xenobiotic metabolism is presented. In general, the catalytic activities of the various renal enzymes are lower than those of the liver, although there are exceptions, such as the enzymes involved in the processing of glutathione conjugates to their mercapturic acids. Xenobiotic metabo-lizing enzymes are not evenly distributed along the nephron; cytochromes P-450 and those enzymes involved in the conjugation of glutathione, glucuronic acid, or sulfate are primarily localized in the proximal tubules. However, some isozymes of cytochrorne(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. Thus, the proximal tubule, the principal site of xenobiotic biotrans-formation, is particularly susceptible to chemical insult, and the localization of prostaglandin synthase in the inner medulla and papilla may be a'contributary factor to the toxicity produced by chemicals in this part of the nephron. Many of the enzymes discussed, in addition to metabolizing foreign compounds, have important endogenous functions in the kidney, such as the regulation of salt and water balance and the synthesis of vitamin D. epoxide hydrolases; renal prostaglandin H synthase; renal cysteine conjugate p-lyase; renal flavin monooxygenases h'eyr.ords. Renal cytochromes P-450; renal glutathione S-transferases; renal glucuronosyl transferases; renal sulfotransferases; rena