Biochemistry 9

The correct answer is:

B) Delavirdine

The Lineweaver-Burk plot can be used to visualize the type of inhibition that a drug exerts on an enzyme. Understanding how an enzyme's V and K_m are represented in the plot is essential for answering these types of questions on the exam.

V is the velocity, or the rate at which an enzyme works on its substrate; V_max is the enzyme's maximum rate. On the Lineweaver-Burk plot, the y-axis is 1/V, or the inverse of the velocity. The y-intercept (where the line crosses the y-axis) is 1/V_max. Thus, the steeper the slope of the line, the higher the y-intercept, the larger the value of 1/V_max, and the smaller the enzyme's velocity V_max.

K_m represents the inverse of an enzyme's affinity for a substrate S (so an increasing Kmindicates a decreasing affinity for substrate). On the Lineweaver-Burk plot, the x-axis is 1/[S], or the inverse concentration of the substrate. The x-intercept (where the line crosses the x-axis) is 1/Km. Thus, as the line shifts to the right, the x-intercept approaches 0, Kmincreases, and the enzyme's affinity for substrate decreases.

The two most common types of inhibition are competitive inhibition and noncompetitive inhibition.

A competitive inhibitor structurally looks like the enzyme's normal substrate and will compete with the substrate for the enzyme's active site. A competitive inhibitor therefore lowers the enzyme's affinity for the substrate, increasing K_m. There is no effect on V_max. On the Lineweaver-Burk plot, since only K_m increases, the x-intercept approaches 0 but the y-intercept (1/V_max) remains unchanged.

A noncompetitive inhibitor will inhibit the enzyme at a site that is different than the active site, lowering the enzyme's V_max. There is no effect on K_m. On the Lineweaver-Burk plot, since only V_max decreases, the y-intercept (1/V_max) increases but the x-intercept (-1/K_m) remains unchanged.

In this question, the red line in the plot demonstrates noncompetitive inhibition: the x-intercept (-1/K_m) is unchanged, and the y-intercept (1/V_max) has increased. Delavirdine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which binds to a site that differs from the active site of HIV reverse transcriptase and noncompetitively inhibits the enzyme.

Answer choice A: Darunavir, is incorrect. Darunavir inhibit HIV protease and does not inhibit reverse transcriptase.

Answer choice C: Didanosine, is incorrect. Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) and resembles the normal nucleoside substrates of HIV reverse transcriptase, thereby competitively inhibiting the enzyme. The Lineweaver-Burk plot in the question displays noncompetitive inhibition, not competitive inhibition.

Answer choice D: Dolutegravir, is incorrect. Dolutegravir inhibits HIV integrase and does not inhibit reverse transcriptase.

Answer choice E: Zidovudine, is incorrect. Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) and resembles the normal nucleoside substrates of HIV reverse transcriptase, thereby competitively inhibiting the enzyme. The Lineweaver-Burk plot in the question displayed noncompetitive inhibition, not competitive inhibition.

Key Learning Point

On a Lineweaver-Burk plot, competitive inhibition is marked by a rightward-shift (x-intercept approaches 0, y-intercept is unchanged), whereas noncompetitive inhibition is marked by an increase in slope (y-intercept increases, x-intercept is unchanged). Non-nucleoside reverse transcriptase inhibitors (NRTIs) such as delavirdine inhibit HIV reverse transcriptase noncompetitively.