Impact of detergents on the activity of acetylcholinesterase and on the effectiveness of its inhibitors
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Martina Zimmermann
Abstract
Acetylcholinesterase (AChE) plays a central role in the development of Alzheimer's disease: AChE inhibition for preventing the characteristic dwindling of acetylcholine levels constitutes the current standard treatment for the disorder. Amongst the diverse risk factors contributing to the degenerative process, high cholesterol causes a reduction in the effectiveness of the otherwise therapeutic inhibitors of AChE. Our biochemical study on the activity of AChE elucidates the effect of amphiphilic molecules on the activity and kinetics of AChE, and sheds light onto the nature of the impact of these amphiphilic molecules on enzyme-inhibitor interactions. Using kinetic studies we discovered that detergents alter the enzymatic activity of AChE through an uncompetitive mechanism. Additional experiments using AChE inhibitors (amphiphilic procaine hydrochloride, hydrophobic tetrabutylammonium bromide) in the absence or presence of detergent further illustrate the detergent-enzyme-solvent interactions. The results contribute to the understanding of the importance of hydrophobic-lipophilic interactions for the correct function of AChE and its inhibitors. We present a model system for the study of lipid-related alterations in the activity of isolated AChE in the central nervous system. This model may also be used to assess and predict the effectiveness of AChE inhibitors, which are traditionally used for the treatment of cognitive impairment, under pathological (high-cholesterol) conditions.
©2009 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Editor's Note
- Editor's Note
- Protein Structure and Function
- Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence
- Biochemical characterization of the catalytic domains of three different clostridial collagenases
- Impact of detergents on the activity of acetylcholinesterase and on the effectiveness of its inhibitors
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- Glycosphingolipids from bovine milk and milk fat globule membranes: a comparative study. Adhesion to enterotoxigenic Escherichia coli strains
- Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells
- Cell Biology and Signaling
- Heavy metals induce phosphorylation of the Bcl-2 protein by Jun N-terminal kinase
- Fibroblast growth factor 2 (FGF-2) is a novel substrate for arginine methylation by PRMT5
- Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling
- Active immunisation against gastric inhibitory polypeptide (GIP) improves blood glucose control in an animal model of obesity-diabetes
- Novel Techniques
- Applicability of superfolder YFP bimolecular fluorescence complementation in vitro
Articles in the same Issue
- Editor's Note
- Editor's Note
- Protein Structure and Function
- Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence
- Biochemical characterization of the catalytic domains of three different clostridial collagenases
- Impact of detergents on the activity of acetylcholinesterase and on the effectiveness of its inhibitors
- The ADP-ribosylating thermozyme from Sulfolobus solfataricus is a DING protein
- Membranes, Lipids, Glycobiology
- Glycosphingolipids from bovine milk and milk fat globule membranes: a comparative study. Adhesion to enterotoxigenic Escherichia coli strains
- Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells
- Cell Biology and Signaling
- Heavy metals induce phosphorylation of the Bcl-2 protein by Jun N-terminal kinase
- Fibroblast growth factor 2 (FGF-2) is a novel substrate for arginine methylation by PRMT5
- Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling
- Active immunisation against gastric inhibitory polypeptide (GIP) improves blood glucose control in an animal model of obesity-diabetes
- Novel Techniques
- Applicability of superfolder YFP bimolecular fluorescence complementation in vitro
