Kelling C K, Van Rafelghem M J, Drake R L, Menahan L A, Peterson R E
School of Pharmacy, University of Wisconsin, Madison 53706.
J Biochem Toxicol. 1986 Sep;1(3):23-37. doi: 10.1002/jbt.2570010304.
Perfluorodecanoic acid (PFDA) administration to adult male rats increased both the activity of hepatic malic enzyme and liver weight in a dose-dependent manner. Hepatomegaly and augmented activity of malic enzyme in liver were apparent within one day following PFDA administration and reached a plateau by three days posttreatment. Malic enzyme quantity per liver in PFDA-treated rats was elevated within one day following dosing and increased continually throughout five days posttreatment. Administration of PFDA to rats in the fed state also led to an increase in the specific activity of hepatic malic enzyme that peaked at three days following dosing. When compared to the fed condition, rats fasted for 48 hours had a decrease in both relative liver weight and the quantity of supernatant protein per liver. The total activity (U/liver) and specific activity of malic enzyme in the liver were also reduced in the fasted state. During the 24 hours after treatment in rats fasted for 48 hours, the body weight as well as the absolute and relative liver weight of animals receiving vehicle declined continuously in the absence of feed. Following the administration of PFDA to fasted rats, body weight was maintained until eight hours posttreatment but then declined at a rate similar to that found with the vehicle-treated group. Absolute and relative liver weight in PFDA-treated rats were increased significantly at eight hours posttreatment when compared to those receiving vehicle, and this increment was maintained throughout the rest of the 24 hours following dosing. While the activity and enzyme content of hepatic malic enzyme decreased in the vehicle-treated group, administration of PFDA to rats fasted for 48 hours prevented their decline. The specific activity of hepatic malic enzyme in 48 hours fasted rats receiving PFDA was also elevated significantly at 16 hours posttreatment. Thus, the administration of PFDA to the adult male rat in both the fed and fasted nutritional states was found to regulate hepatic malic enzyme by not only increasing enzyme quantity but also by augmenting the specific activity, (ie, catalytic state) of the enzyme.
给成年雄性大鼠施用全氟癸酸（PFDA）会以剂量依赖的方式增加肝脏苹果酸酶的活性和肝脏重量。在施用PFDA后的一天内，肝脏肿大和肝脏中苹果酸酶活性增强就很明显，并在治疗后三天达到平台期。PFDA处理的大鼠肝脏中苹果酸酶的量在给药后一天内升高，并在治疗后的五天内持续增加。给处于进食状态的大鼠施用PFDA也会导致肝脏苹果酸酶的比活性增加，在给药后三天达到峰值。与进食状态相比，禁食48小时的大鼠相对肝脏重量和每肝脏上清液蛋白量均降低。禁食状态下肝脏中苹果酸酶的总活性（U/肝脏）和比活性也降低。在禁食48小时的大鼠治疗后的24小时内，接受赋形剂的动物在没有食物的情况下体重以及绝对和相对肝脏重量持续下降。给禁食大鼠施用PFDA后，体重在治疗后八小时内保持稳定，但随后以与赋形剂处理组相似的速率下降。与接受赋形剂的大鼠相比，PFDA处理的大鼠在治疗后八小时绝对和相对肝脏重量显著增加，并且这种增加在给药后的其余24小时内一直保持。虽然赋形剂处理组肝脏苹果酸酶的活性和酶含量降低，但给禁食48小时的大鼠施用PFDA可防止其下降。接受PFDA的48小时禁食大鼠肝脏苹果酸酶的比活性在治疗后16小时也显著升高。因此，发现在进食和禁食营养状态下给成年雄性大鼠施用PFDA不仅通过增加酶量而且通过增强酶的比活性（即催化状态）来调节肝脏苹果酸酶。
