Eid_1981_Biochemistry_20_2251

Methyl(acetoxymethyl)nitrosamine and methyl-(butyroxymethyl)nitrosamine are respectively substrate KM 10(-2 M and competitive inhibitor Ki 2 x 10(-3 M of electric eel acetylcholinesterase EC 3.1.1.7 Irradiation of an incubation mixture of this enzyme with either nitrosamine leads to an irreversible loss of enzyme activity The inactivation rates are dependent on photolysis wavelength light intensity and inhibitor concentration Experiments where acetylcholinesterase was radioactively labeled by 14C methyl(acetoxymethyl)nitrosamine show that the incorporation of 1 mol of radioactive label per active site is sufficient to cause complete enzyme inactivation irrespective of the reaction conditions used Methyl(acetoxymethyl)nitrosamine shows no affinity while methyl(butyroxymethyl)nitrosamine is a competitive inhibitor Ki 2 x 10(-3 M but no irreversible inhibition is induced by the action of light We propose that a suicide type of inhibition Bloch K 1969 Acc Chem Res 2 193-198 is responsible for the inactivation of acetylcholinesterase based on photoactivation of nitrosamines only when associated with an acidic hydrogen of the active site