Author/Editor		Štalc, A; Šentjurc, M
Title		A contribution to the mechanism of action of SAD-128
Type		članek
Source		Biochem Pharmacol
Vol. and No.		Letnik 40, št. 11
Publication year		1990
Volume		str. 2511-7
Language		eng
Abstract		SAD-128 was found to be an effective protector of acetylcholinesterase against inhibition by soman, due to its ability to function as a reversible inhibitor and allosteric modifier of the AChE active site. It also attenuated aging of the soman-inhibited enzyme. In order to study the connection between some of these effects of SAD-128 and structural changes in acetylcholinesterase and/or the membrane to which the enzyme is bound, the influences of SAD-128 on the EPR spectra of the spin labelled enzyme and of the membrane were studied under various conditions and the results correlated with the kinetic parameters. SAD-128 increases the fluidity of human erythrocyte membranes but not that of the Torpedo marmorata electric organ. Similarly, the binding properties of membrane acetylcholinesterase for SAD-128, expressed in terms of the Hill coefficient, differ for the two preparations. Some structural changes in the enzyme active site were also observed in the presence of SAD-128. The high protective effect of SAD-128 against AChE inhibition was confirmed by the EPR method regardless of the organophosphorus inhibitor tested. On the other hand, the effect of SAD-128 on the retardation of irreversible inhibition of the enzyme essentially depends on the inhibitor used. From present results it can be concluded that the protective effects of SAD-128 against inhibition of m-AChE are related to the structural changes of the active site and can be additionally moderated by the microviscosity changes of the membrane.
Descriptors		CHOLINESTERASE INHIBITORS PYRIDINIUM COMPOUNDS BINDING SITES ELECTRIC ORGAN ELECTRON SPIN RESONANCE SPECTROSCOPY MEMBRANE FLUIDITY ORGANOPHOSPHORUS COMPOUNDS