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Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase
Authors:Andrew W Brown  Jiliang Hang  Patrick H Dussault  Timothy P Carr
Institution:1. Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE 68583-0806, USA;2. Department of Chemistry, University of Nebraska, Lincoln 68583-0304, NE, USA;1. School of Chemistry & Chemical Engineering, Sun Yat-sen University, 135 Xingangxi Lu, Guangzhou 510275, China;2. College of Bioscience and Biotechnology, Hunan Agricultural University, Furong District, Changsha 410428, China;1. Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China;2. Department of Research and Development, Conba Pharmaceutical Co., Ltd., Hangzhou 310050, China;1. Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;2. Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;3. Molecular Medicine Program, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand
Abstract:Consumption of plant sterols or stanols (collectively referred to as phytosterols) and their esters results in decreased low-density lipoprotein cholesterol, which is associated with decreased atherosclerotic risk. The mechanisms by which phytosterols impart their effects, however, are incompletely characterized. The objective of the present study is to determine if pancreatic cholesterol esterase (PCE; EC 3.1.1.13), the enzyme primarily responsible for cholesterol ester hydrolysis in the digestive tract, is capable of hydrolyzing various phytosterol esters and to compare the rates of sterol ester hydrolysis in vitro. We found that PCE hydrolyzes palmitate, oleate and stearate esters of cholesterol, stigmasterol, stigmastanol and sitosterol. Furthermore, we found that the rate of hydrolysis was dependent on both the sterol and the fatty acid moieties in the following order of rates of hydrolysis: cholesterol>(sitosterol=stigmastanol)>stigmasterol; oleate>(palmitate=stearate). The addition of free phytosterols to the system did not change hydrolytic activity of PCE, while addition of palmitate, oleate or stearate increased activity. Thus, PCE may play an important but discriminatory role in vivo in the liberation of free phytosterols to compete with cholesterol for micellar solubilization and absorption.
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