Characterization of human erythrocyte membrane-bound acetylcholinesterase inhibition by cisplatin at reversible phase.

Acetylcholinesterase (AChE) is a perfect hydrolyzing enzyme, and it has been recently reported [Al-Jafari et al 1995; Kamal and Al-Jafari, 1996] that cisplatin, which is cytotoxic, has the ability to inhibit the AChE activity in vitro. I therefore studied the characterization of this inhibition with respect to establishment of kinetic parameters at the reversible stage only. Conventional kinetic methods have been used in the present study. Some secondary replots, equilibrium schemes and some equations for this type of inhibition are novel for precise kinetic analysis in this inhibition system. The Michaelis-Menten constant (Km) for the hydrolysis of acetylthiocholine iodide (ASCh) was found to be 0.0994 mM and the Vmax was 1.179 mumol/minute/mg protein. The Kmapp and Vmaxapp were both decreased by increasing cisplatin concentrations. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the pure uncompetitive type. The value of Ki was estimated as 3.593 mM by the primary and secondary replots of the Lineweaver-Burk plot and Dixon plot. The Kiapp decreased while Vmaxiapp increased with increases in the ASCh concentration. This opens the possibilities for explaining the mechanism of AChE interaction with cisplatin as well as approaches towards understanding the causes of the neuro-type side effects of this drug.