title: [Kinetics of the N,N-dimethyl-2-phenylaziridinium reaction with a muscarinic cholinoreceptor and acetylcholinesterases].
abstract: Kinetics of the reaction of N,N-dimethyl-2-phenylaziridinium ions with soluble acetylcholinesterases from cobra venom and electric eel as well as with the membrane-bound acetylcholinesterase and the muscarinic acetylcholine receptor from the cerebral cortex of rat brain was investigated at pH 7,5 and 25 degrees C in 0,15 M phosphate buffer. The inhibition reaction involves the non-covalent binding step followed by the irreversible alkylation step. The spontaneous hydrolysis of the aziridinium compound and the reversible inhibition of the enzymes with the hydrolytic product were taken into account in data treatment. The aziridinium ions were found to bind with similar effectiveness in the active centers of acetylcholinesterases and the muscarinic acetylcholine receptor, however, for the latter the alkylation step is more than 10-fold faster. This difference can be explained by different solvation effects exerted by the active centers of these proteins. The rate constants of the protein alkylation reaction are compared with the kinetic data for decomposition reaction of the aziridinium ion in several solvent-water mixtures, studied separately in the case of five solvents. The basicity of the solvents was found to be the most important factor accelerating the solvolysis.
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000478:Alkylation; D000818:Animals; D001388:Aziridines / Q000378:metabolism* / Q000494:pharmacology; D001389:Azirines / Q000378:metabolism*; D001665:Binding Sites; D002540:Cerebral Cortex / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004546:Elapid Venoms / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001388:Aziridines; D001389:Azirines; D002800:Cholinesterase Inhibitors; D004546:Elapid Venoms; D011976:Receptors, Muscarinic; C001054:N,N-dimethyl-2-phenylaziridinium; D000110:Acetylcholinesterase
vernacular_title: Kinetika reaktsii N,N-dimetil-2-fenilaziridiniia s muskarinovym kholinoretseptorom i atsetilkholinésterazami.