(30) H 2O 2 modifies membrane structure and activity of acetylcholinesterase

Abstract

The main factor of Alzheimer disease (AD) is β-amyloid peptide (Aβ). It is known to affect acetylcholinesterase (AChE) through lipid peroxidation (LPO) initiated with H 2O 2 which is formed as a result of Aβ activity. The direct action of H 2O 2 on the enzyme is also possible. For membrane bound AChE of erythrocytes we observed inhibition under H 2O 2 action which was replaced by activation at small H 2O 2 concentrations. At higher substrate concentrations the inversion of the effect came at smaller concentrations of H 2O 2. For soluble erythrocytic AChE inhibition took place (caused by K m increase). Soluble enzyme from Electric Eel revealed inhibition, which was not replaced by activation at any concentration of peroxide. Low H 2O 2 concentrations caused intensification of lipid peroxidation in microsomes. The magnitude of the changes in LPO rate was within the range of the changes, where LPO system fulfills the control function for cell metabolism. With the help of ESR technique of spin probes it was found the rigidization under H 2O 2 action of close to surface area of lipid bilayer in erythrocytic and brain cell membranes. Summing up we can say that H 2O 2 modifies membrane structure and activity of AChE. Whether or not it will contribute to AD pathogenesis or is the manifestation of compensatory processes—the possible subject of discussion and further investigation.