Sisková K, Bilka F, Adameová A, Balazová A, Mydla M, Pauliková I
Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic.
Pharmazie. 2012 Apr;67(4):345-50.
Butyrylcholinesterase (EC 3.1.1.8, BChE) is highly active in plasma, skin and lung, the tissues that first contact xenobiotics, supporting a role for BChE in detoxication of xenobiotics including medicaments. A possible involvement of BChE in lipid metabolism has been suggested. Elevated BChE activity in obese individuals correlates with some parameters of lipid metabolism including increased levels of triacylglycerols (TAG) and cholesterol. The aim of this study was to estimate the BChE activity in rats on subcellular and inter-organ levels under the conditions of untreated and treated primary hypertriacylglycerolemia with the TAG lowering agent fenofibrate. No changes in BChE activity were observed in obese animals. However fenofibrate administration led to significant increase of BChE activity in all examined tissues (plasma, liver, white adipose tissue). The impact of lipid metabolic imbalance on BChE biotransformation ability was tested by measuring the rate of hydrolysis of 0,1 to 8 mM concentrations of the antimicrobial agent N-(2-benzoyloxyethyl)-ethyldimethylammonium bromide (BCH2). The results revealed a complete shift in the BChE kinetics in all studied models. In animals with hypertriacylglycerolemia the Km value of liver BChE rised 4,6-fold, but the total enzyme efficiency expressed as Vmax/Km dropped 40% comparing to control. In contrast, in animals treated with fenofibrate the BChE efficiency increased in liver 1,6-fold. We conclude here that BChE detoxification capacity is essentially altered under conditions of disturbed lipid metabolism. Clinically, this knowledge could be important in a view of xenobiotic elimination, especially when routinely prescribed medicaments are concerned.
丁酰胆碱酯酶（EC 3.1.1.8，BChE）在血浆、皮肤和肺等最先接触外源性物质的组织中具有高活性，这支持了BChE在包括药物在内的外源性物质解毒过程中的作用。有人提出BChE可能参与脂质代谢。肥胖个体中升高的BChE活性与脂质代谢的一些参数相关，包括三酰甘油（TAG）和胆固醇水平的升高。本研究的目的是在未治疗和用TAG降低剂非诺贝特治疗原发性高三酰甘油血症的条件下，在亚细胞和器官间水平评估大鼠的BChE活性。在肥胖动物中未观察到BChE活性的变化。然而，给予非诺贝特导致所有检测组织（血浆、肝脏、白色脂肪组织）中BChE活性显著增加。通过测量0.1至8 mM浓度的抗菌剂N-(2-苯甲酰氧基乙基)-乙基二甲基溴化铵（BCH2）的水解速率，测试了脂质代谢失衡对BChE生物转化能力的影响。结果显示，在所有研究模型中BChE动力学发生了完全改变。在患有高三酰甘油血症的动物中，肝脏BChE的Km值升高了4.6倍，但以Vmax/Km表示的总酶效率与对照组相比下降了40%。相反，在用非诺贝特治疗的动物中，肝脏中BChE效率提高了1.6倍。我们在此得出结论：在脂质代谢紊乱的情况下，BChE的解毒能力发生了本质改变。从临床角度来看，鉴于外源性物质的消除，尤其是涉及常规处方药物时，这一知识可能很重要。
