Problem Set 8

1. Draw two plots (A and B together, then A and C together) that show how an enzyme-catalyzed reaction rate (velocity) varies with substrate concentration. For Case A, there is no inhibitor present. For Case B, there is a competitive inhibitor present. For Case C, there is a noncompetitive inhibitor present. Be sure to show the K_M and the V_max for each of the three cases on the two plots. Clearly describe the difference between competitive and noncompetitive inhibitors.

2. Examination of a receptor interaction study of three drugs undergoing clinical trials revealed K_d’s of 40 nM, 2 mM, and 900 pM for Drugs A, B, and C respectively. Drug A was found to have greatest efficacy, while Drug B was found to have the lowest efficacy.

a. Draw a dose-response plot that illustrates the curves for drugs A, B and C.

b. Clearly define what is specifically meant by a drug’s efficacy and potency

c. Describe the relative potency and efficacy for drugs A, B, and C; clearly support your answer.

d. Compare the relative affinities of the three drugs for the receptor binding site and clearly support your answer.

3. The K_M for an enzyme catalyzed reaction at a temperature of 310K was found to be 10 mM. Determine the substrate concentration at which 80% of the enzyme molecules have their active sites occupied by the substrate.

4. A recent enzyme-catalyzed reaction study revealed the following reaction rates for various substrate concentrations. An enzyme concentration of 10 mM was used for all runs. Using the data listed in the table below, answer each of these questions:

[S] mM	Velocity (M/min)
0.10	3.33
0.20	5
0.50	7.14
0.80	8
1.00	8.33
2.00	9.09

a. Construct a Lineweaver-Burk plot of these data; show both the data and the plot.

b. Do a linear fit to these data; determine the slope and intercept.

c. Determine K_M and V_max

d. Determine the turnover number for the enzyme used in this reaction.