Kinetics of the inhibition of acetylcholinesterase in camel retina by cisplatin.
The inhibitory effect of cisplatin (CDDP) on camel retina acetylcholinesterase (AChE) was characterized. The CDDP effect was independent of the time of incubation with AChE before the addition of substrate, indicative of reversible inhibition. Moreover, dilution data prove that CDDP is a reversible inhibitor of camel retina AChE. Cisplatin inhibited AChE activity of camel retina in a concentration- and time-dependent manner, the IC50 values being 5.32 and 0.196 mM at 5 min and 24 h incubation times, respectively. The IC50 has dual components, i.e. directly proportional and inversely proportional to 0-1.5 h and 1.5-24 h incubation periods, respectively. The Michaelis-Menten constant (Km) for the hydrolysis of acetylthiocholine iodide (ASCh) was found to be 0.0796 mM and Vmax was 0.668 micromol/min/mg protein. Kmapp and Vmaxapp both decreased as the CDDP concentration increased. 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 0.811 mM by the primary and secondary replots of the Lineweaver-Burk and Dixon plots. Kiapp decreased while Vmaxiapp increased after increasing the ASCh concentration.
Al-Jafari
A A
AA
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. jafari@ksu.edu.sa
Al-Khwyter
F
F
Kamal
M A
MA
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002162:Camelus; D002945:Cisplatin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D012160:Retina / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000110:Acetylcholinesterase; D002945:Cisplatin