Simvastatin Vocork), Mr 419) and lovastatin (Mevacorffi, Mr 404) are widely used cholesterol-lowering drugs that work by competitively inhibiting 3-hydroxy-3-methyl. /1coemyme A reducta., which catalyze a major rate-limiting step in the cholesterol bMsynthesis pathway.Their Ki values are 0.1 . and 3.4 ., respectively. These drugs have also been shown to reversibly ivhibit acetyltholinesterase (AChE, EC 3.1.1.7).
Another AChE inhibitor is done. (Ariceptill, Mr 379) which has been approved to treat the symptoms of Alzheimer's disease, the idea being that it helps overcome a depleted cholinergic system, especially in the cerebral cortex.
The following data are representative of studies of these inhibitors using AChE purified from the Pacific electric ray. Each reaction was 1.0 ml and contained 12 fmol AChE.
Use all the above d. and Excel to make a diagnostic Lineweaver-Burk plot, with trend line equations displayed on the plot, to answer the following questions:
a. What are K., Vet,,, and K„, for the ray AChE? (There is 1 active site per molecule.)
b. What is the analytic efficiency of the enzyme? How does this compare to the most efficient enzymes? (Express any differen. in terms of orders of magnitude.)
c. What type of AChE inhibitor is each of the inhibitors? Justify your answers.
d. What are the K's for the three inhibitors? Which is the better inhibitor? Justify your answer.
e. The typical dose for each of these drugs is a 10-20 mg tablet daily. At this dosage would an Alzheimm's patient expect any effect on their dementia from the statin they take for hypercholmteremia? Explain why? Math calculation not needed, but you may do so.