Selective changes in cytochrome P-450 and UDP-glucuronosyltransferase subpopulations following partial hepatectomy in rats

Abstract

Following 65% hepatectomy in adult male rats, the cytochrome P-450 in the residual liver decreased continuously from 1.0 to approximately 0.5 nmol/mg protein over a period of 2 to 3 days, and then recovered slowly to presurgety values by 14 days. In contrast UDP-glucuronosyltransferase activity (per mg protein) declined (25 to 40% depending on the aglycone used to assay the enzyme) for only 1 day, with a rapid recovery to presurgery values by 5 days. Transferase activity toward estrone overshot control values during recovery and was elevated above its presurgery value at 7 days. The changes in drugmetabolizing enzymes were accompanied by a surge inmitosis which peaked at 2 days. The extent of the decline in cytochrome P-450 and the increase in the mitotic index were proportional to the amount of liver removed. The decline in cytochrome P-450 was selective for cytochrome P-450 which elutes in the void volume upon anion-exchange high-pressure liquid chromatography of solubilized microsomes. Accompanying the decline in cytochrome P-450 in this eluate was a decline in protein(s) with a molecular weight of 51,500. The decline in cytochrome P-450 also caused disproportionate decreases in microsomal ethylmorphine N-demethylase activity and metabolic-intermediate complex formation from norbenzphetamine and SKF 525-A, but not in p-nitroanisole O-demethylase activity, metabolic-intermediate complex formation from isosafrole or metyrapone binding to cytochrome P-450.