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Q58 — TAK1 Kinase and Takinib — Competitive vs Non-Competitive Inhibition

Theoretical 2 Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license
Enzyme Kinetics & Regulation

TAK1 is a protein kinase which transfers a phosphate group from ATP to a substrate. In order to elucidate the action mechanism of Takinib, a novel inhibitor of TAK1, two experiments were carried out. In experiment A, TAK1 was added to the solution of ATP, Takinib and TAK1 substrate, and the initial reaction rate was measured for different ATP concentrations and different amounts of Takinib. In experiment B, TAK1 was pre-incubated with 5 μM ATP for 3 hours and then the same steps as in experiment A were carried out with the pre-incubated TAK1. The results of experiments A and B are summarized below, with the amount of inhibitor used indicated to the right.

Figure. Panel A: initial reaction rate vs [ATP] for TAK1 not pre-incubated, at 0, 10, and 50 nM Takinib — Vmax drops with increasing Takinib while the curves rise at a similar rate. Panel B: same but with TAK1 pre-incubated with ATP for 3 hours — curves converge to a similar Vmax regardless of Takinib concentration. Figure. Dependence of initial reaction rate on starting ATP concentration, at different Takinib doses, without (A) and with (B) ATP pre-incubation.

Determine whether the following statements are true or false:

A. If TAK1 is pre-incubated with 5 μM ATP for 3 hours, then Takinib, added later, acts as a competitive inhibitor.
B. In both experiments, Takinib significantly affects TAK1's Michaelis constant with respect to ATP.
C. Experiments A and B indicate that TAK1 has another interaction site, in addition to the enzymatic active center.
D. If TAK1 was not pre-incubated, then the presence of Takinib could be compensated by an excess of ATP.
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Question reproduced from IBO 2022, Theoretical Paper 2, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)