Abstract：
Over the course of the last twenty years, there has been a growing recognition of the pig\'s potential as a valuable model for studying human drug metabolism. This study aimed to investigate the expression, enzymatic activity, inhibitory susceptibility, and cellular localization of carboxylesterases (CES) in porcine lung tissue not yet explored. Our results showed that CESs hydrolysis activity followed Michaelis-Menten kinetics in both cytosolic and microsomal fractions of porcine lung tissues (N = 8), with comparable hydrolysis rates for tested substrates, namely 4-nitrophenyl acetate (pNPA), 4-methylumbelliferyl acetate (4-MUA), and fluorescein diacetate (FD). We also determined the CESs hydrolysis activity in a representative sample of the porcine liver that, as expected, displayed higher activity than the lung ones. The study demonstrated variable levels of enzyme activities and interindividual variability in both porcine lung fractions. Inhibition studies used to assess the CESs\' involvement in the hydrolysis of pNPA, 4-MUA, and FD suggested that CESs may be the enzymes primarily involved in the metabolism of ester compounds in the pig lung tissue. Overall, this study provides insight into the distribution and diversity of CES isoforms involved in substrate hydrolysis across different cellular fractions (cytosol and microsomes) in porcine lungs.
摘要：
在过去的二十年里，人们越来越认识到猪作为研究人类药物代谢有价值的模型的潜力。本研究旨在探讨其表达，酶活性，抑制性易感性，和羧酸酯酶（CES）在猪肺组织中的细胞定位尚未探索。我们的结果表明，在猪肺组织的胞浆和微粒体部分（N=8）中，CESs的水解活性遵循米氏-Menten动力学，对于测试的底物，具有可比的水解速率，即乙酸4-硝基苯酯（pNPA），乙酸4-甲基伞形酯（4-MUA），和荧光素二乙酸酯(FD)。我们还确定了猪肝脏代表性样品中的CESs水解活性，正如预期的那样，显示出比肺更高的活性。该研究证明了两种猪肺部分中不同水平的酶活性和个体间变异性。用于评估CESs参与pNPA水解的抑制研究，4-MUA,FD提示CESs可能是猪肺组织中主要参与酯化合物代谢的酶。总的来说,这项研究提供了有关CES同工型在猪肺中不同细胞部分（细胞溶胶和微粒体）中参与底物水解的分布和多样性的见解。
