Selective changes in cytochrome P-450 and UDP-glucuronosyltransferase subpopulations following partial hepatectomy in rats.
Selective changes in cytochrome P-450 and UDP-glucuronosyltransferase subpopulations following partial hepatectomy in rats.
复制标题
大鼠部分肝切除术后细胞色素 P-450 和 UDP-葡萄糖醛酸基转移酶亚群的选择性变化。
DOI：
10.1016/0041-008x(85)90299-6
复制
发表时间：
1985
影响因子：
3.8
通讯作者：
Franklin,MR
中科院分区：
文献类型：
--
作者：
Iversen,PL;Liu,Z;Franklin,MR
在成年雄性大鼠中进行65%肝切除术后，残留肝脏中的细胞色素P-450在2至3天内从1.0 nmol/mg蛋白质连续下降至约0.5 nmol/mg蛋白质，然后在14天内缓慢恢复至应激前值。相反，UDP-葡萄糖醛酸基转移酶活性（每毫克蛋白质）下降（25至40%，取决于用于测定酶的糖苷配基）仅1天，5天后迅速恢复到术前值。在恢复过程中，雌酮转移酶活性超过对照值，并在7天时升高至高于术前值。药物代谢酶的变化伴随着有丝分裂高峰，高峰出现在第2天。细胞色素P-450的下降程度和有丝分裂指数的增加与肝脏的切除量成正比。细胞色素P-450的下降是选择性的细胞色素P-450，其在溶解的微粒体的阴离子交换高压液相色谱后的空隙体积中洗脱。伴随着细胞色素P-450的下降，在这一时期，蛋白质的分子量为51，500。细胞色素P-450的下降也导致微粒体乙基吗啡N-脱甲基酶活性和去甲苄非他明和SKF 525-A的代谢中间体复合物形成不成比例的降低，但对硝基苯甲醚O-脱甲基酶活性、异黄樟油素或甲吡酮与细胞色素P-450结合的代谢中间体复合物形成不成比例的降低。
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.