Dihydrouracil dehydrogenase activity in normal, differentiating and regnerating liver and in hepatomas.
Dihydrouracil dehydrogenase activity in normal, differentiating and regnerating liver and in hepatomas.
复制标题
正常、分化和再生肝脏以及肝癌中的二氢尿嘧啶脱氢酶活性。
作者：
S. Queener;H. Morris;G. Weber
比较了二氢尿嘧啶脱氢酶活性（4,5-二氢尿嘧啶：NADP氧化还原酶，EC 1.3.1.2）在正常肝脏（发育大鼠和部分肝切除大鼠）和肿瘤肝脏（不同生长速度的肝癌谱）中的行为。在10万× g上清液中测定酶活性。该酶对底物尿嘧啶的亲和力在肝癌中与同一菌株的正常对照大鼠的肝脏中相似。对照组和肿瘤肝的pH最适值为7.2。大鼠肝脏、胸腺、肠黏膜、脾脏、肾脏、脑、骨骼肌和心脏的二氢尿嘧啶脱氢酶活性分别为2.0、1.1、0.9、0.7、0.6、0.4、0.2和0.1µmol /hr/g（湿重）。在分化肝中，平均细胞的酶活性比新生儿的水平提高了2.7倍，达到成年大鼠肝脏的活性。在部分肝切除术后24小时的再生肝脏中，酶活性下降到假手术对照组的74%。在肝癌谱中，二氢尿嘧啶脱氢酶活性随肝癌生长速率的增加而下降。在生长最迅速的肿瘤（9618A2, 3683F）中，活性约为相同品系、性别、年龄和体重的对照大鼠肝脏中的15%或更少。由于再生肝的增殖速度与快速生长的肝癌相当，因此在肿瘤中观察到的明显减少似乎是肿瘤细胞生长所特有的。二氢尿嘧啶脱氢酶被认为是尿嘧啶分解代谢途径中的限速酶；因此，该酶活性的降低与肝癌生长速度的增加密切相关，为分子相关概念提供了进一步的证据。
Summary The behavior of dihydrouracil dehydrogenase activity (4,5-dihydrouracil:NADP oxidoreductase, EC 1.3.1.2) was compared in proliferating normal liver (from developing rats and from partially hepatectomized rats) and in neoplastic liver (spectrum of hepatomas of different growth rates). The enzyme activity was determined in the 100,000 × g supernatant fluid. The affinity of the enzyme to the substrate, uracil, was similar in the hepatomas to that in the liver of control normal rats of the same strain. The pH optimum of the control and neoplastic livers was at 7.2. The activities of dihydrouracil dehydrogenase in rat liver, thymus, intestinal mucosa, spleen, kidney, brain, skeletal muscle, and heart were 2.0, 1.1, 0.9, 0.7, 0.6, 0.4, 0.2, and 0.1 µmoles/hr/g, wet weight, of tissue at 37°, respectively. In the differentiating liver, the enzyme activity of the average cell increased 2.7-fold from the level observed in the newborn to reach the activity of the liver of adult rat. In the regenerating liver at 24 hr after partial hepatectomy, the enzyme activity decreased to 74% of that of the sham-operated controls. In the spectrum of hepatomas, dihydrouracil dehydrogenase activity decreased in parallel with the increase in hepatoma growth rate. In the most rapidly growing tumors (9618A2, 3683F), the activities were about 15% or less of those in liver of control rats of the same strain, sex, age, and weight. Since the regenerating liver proliferates at a rate comparable to that of the rapidly growing hepatoma, the marked decrease observed in the tumor appears to be specific to neoplastic cell growth. Dihydrouracil dehydrogenase is considered the rate-limiting enzyme in the catabolic pathway of uracil; therefore, the close linking of the decrease in the activity of this enzyme with the increase in hepatoma growth rate provides further evidence in support of the Molecular Correlation Concept.