Kinetic analysis of the toxicological effect of tacrine (Cognex) on human retinal acetylcholinesterase activity.
For the first time, kinetic parameters of the effect of tacrine, an anti-cholinesterase inhibitor of therapeutic potential in Alzheimer's disease has been studied on human retinal acetyl-cholinesterase (AChE). Tacrine inhibited the AChE activity in a concentration dependent manner, the IC(50) being about 45 nM. The Michaelis-Menten constant (K(m)) for the hydrolysis of acetylthiocholine iodide was found to be 0.120 mM and this value was increased by 4-52.8% in the presence of tacrine. V(max) was observed to be 2.23 micromol/h per mg protein for the control system, while it was decreased by 14.73-56.25% in the tacrine treated systems. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the mixed type, i. e. a combination of competitive and noncompetitive inhibition. The values of K(i) and K(I) were estimated to be as 37.76 and 64.36 nM, respectively.
Alhomida
A S
AS
Department of Biochemistry, College of Science, King Saud University, PO Box 2455, 11451, Riyadh, Saudi Arabia.
Al-Rajhi
A A
AA
Kamal
M A
MA
Al-Jafari
A A
AA
D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D018697:Nootropic Agents / Q000633:toxicity*; D012160:Retina / Q000187:drug effects / Q000201:enzymology*; D013619:Tacrine / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D005136:Eye Proteins; D018697:Nootropic Agents; D013619:Tacrine; D000110:Acetylcholinesterase