engleski

Mechanism of interaction of oximes with acetylcholinesterase and butyrylcholinesterase

The binding of pyridinium and imidazolium oximes, coumarin derivatives and 4, 4"-bipyridine to the allosteric and catalytic sites of cholinesterases are discussed. The two binding sites in acetylcholinesterase (AChE) were studied by evaluating the kinetics of competition between substrates (choline and thiocholine esters) and the ligands. In the presence of the ligands, phosphorylation of AChE by organophosphorus compounds decreased. The extent of decrease varied with the enzyme/ligand dissociation constants of both the allosteric and catalytic binding sites. Phosphorylation of the catalytic site did not alter the affinity of the allosteric site for the ligands studied. The same approach when applied to butyrylcholinesterase (BuChE) suggested that BuChE might also have two binding sites for the ligands. This was shown by the kinetics of inhibition with 4, 4"-bipyridine of the human serum BuChE phenotypes. UU, FS and AA phenotypes had about the same affinity for 4, 4"-bipyridine and also for pyridinium oximes P2AM and HI-6. Oximes catalysed the non-enzymic hydrolysis of acetylthiocholine thereby causing a limiting factor in studies of enzyme activity at high substrate and oxime concentrations.

acetylcholinesterase; butyrylcholinesterase; oximes; binding sites on cholinesterases; reversible inhibition of cholinesterases; protection against phosphorylation; organophosphorus compounds

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