KINETICS OF HUMAN ERYTHROCYTE ACETYLCHOLINESTERASE INHIBITION BY CIS-DIAMMINEDIAQUAPLATINUM(II)

This work addresses the kinetic studies for the interaction of cis-dia mminediaquaplatinum (II) {cis-[Pt(NH3)2(H2O)2](2+)}, (DDP) with human erythrocyte acetylcholinesterase (AChE). The K-S for the hydrolysis of acetylthiocholine iodide (ASCh) by AChE was 0.077 mM in the control s ystem, the value decreased by 14-38% in the DDP treated systems. The V -max was 1.34 mu mole/min/mg protein for the control system while it w as decreased by 26-57% in the DDP treated systems. The Lineweaver-Burk plot, Dixon plot and their secondary replots indicated that the natur e of the inhibition was of the linear mixed type, i.e. uncompetitive a nd noncompetitive. The values of K-i and K-i were estimated as 0.203 a nd 0.096 mM, respectively. The estimated values of K-i and K-1 in the present investigation were compared with reported values for human ery throcyte and camel retina AChE inhibition by some antineoplastic drugs : cisplatin, cyclophosphamide and methotrexate.