An enzyme has Km = 2 mM and Vmax = 100 nmol/min in the absence of inhibitor. A competitive inhibitor is added. What do you expect to observe?
AKm = 2 mM (unchanged), Vmax = 50 nmol/min (decreased)
BKm = 5 mM (increased), Vmax = 100 nmol/min (unchanged)
CKm = 5 mM (increased), Vmax = 50 nmol/min (decreased)
DKm = 2 mM (unchanged), Vmax = 100 nmol/min (unchanged), but reaction is slower at all substrate concentrations
Competitive inhibition's defining kinetic signature is increased apparent Km with unchanged Vmax. The inhibitor competes with substrate for the active site, making the enzyme harder to saturate — requiring more substrate to reach half-maximal velocity (higher Km). But at infinitely high substrate concentration, substrate overwhelms the inhibitor and saturates every enzyme molecule, so the theoretical maximum velocity is unchanged. Option A describes noncompetitive inhibition. Option C describes mixed inhibition. Option D is incorrect because at low substrate concentrations the inhibitor does reduce observed velocity — the curve shifts, but Vmax is the asymptote.
Question 2 Multiple Choice
A Lineweaver-Burk plot (1/V vs 1/[S]) is generated for an enzyme with and without an inhibitor. The two lines have the same y-intercept but different x-intercepts and slopes. What does this pattern indicate?
ANoncompetitive inhibition — Vmax is unchanged (same y-intercept) and Km increases (different x-intercept)
BCompetitive inhibition — Vmax is unchanged (same y-intercept) and apparent Km increases (different x-intercept)
CUncompetitive inhibition — both Km and Vmax decrease proportionally, producing parallel lines
DIrreversible inhibition — the enzyme is permanently modified, reducing Vmax
On a Lineweaver-Burk plot, the y-intercept is 1/Vmax and the x-intercept is −1/Km. Same y-intercept means same Vmax; different x-intercepts mean different apparent Km values. This is the diagnostic fingerprint of competitive inhibition. Noncompetitive inhibition shows different y-intercepts (reduced Vmax) but the same x-intercept (unchanged Km). Uncompetitive inhibition produces parallel lines (both intercepts change proportionally). The convergence at the y-axis uniquely identifies competitive inhibition.
Question 3 True / False
A competitive inhibitor can be fully overcome by adding enough substrate, returning the reaction velocity to Vmax.
TTrue
FFalse
Answer: True
This is the defining pharmacological and kinetic feature of competitive inhibition. Because the inhibitor and substrate compete reversibly for the same active site, increasing substrate concentration shifts the competition in favor of substrate — at sufficiently high [S], essentially all enzyme molecules are occupied by substrate rather than inhibitor, and the reaction proceeds at Vmax. This is why competitive inhibitors have reduced effectiveness when substrate concentrations are high, and why the Ki must be interpreted relative to Km when predicting drug efficacy in vivo.
Question 4 True / False
Competitive inhibition reduces Vmax because the inhibitor prevents some enzyme molecules from ever binding substrate, permanently reducing the pool of active enzyme.
TTrue
FFalse
Answer: False
This describes irreversible inhibition, not competitive inhibition. Competitive inhibitors bind reversibly and do not permanently block any enzyme molecule. At any moment, a competitively inhibited enzyme oscillates between states: sometimes inhibitor-bound (inactive), sometimes substrate-bound (active), sometimes free. Adding more substrate increases the fraction of time spent in the substrate-bound state. Because no enzyme is permanently removed from the active pool, Vmax is unchanged — at saturating [S], all enzyme eventually turns over at the full rate.
Question 5 Short Answer
Why does competitive inhibition increase the apparent Km without changing Vmax? Explain in terms of what is happening at the molecular level.
Think about your answer, then reveal below.
Model answer: Km is the substrate concentration at which the reaction proceeds at half of Vmax. A competitive inhibitor occupies the active site some fraction of the time, effectively reducing the probability that any given active site is available for substrate. To reach 50% saturation of available enzyme molecules, you now need more substrate — hence apparent Km increases. But Vmax is the velocity when every enzyme molecule is saturated with substrate. If substrate concentration is high enough to outcompete the inhibitor for every active site, all enzyme molecules turn over at full speed. The inhibitor slows the approach to saturation (raises Km) but doesn't change the ceiling (Vmax), because it cannot permanently block any enzyme molecule.
Km and Vmax measure different things: Km measures how much substrate is needed to approach saturation (affected by competition for the site), while Vmax measures the catalytic capacity of saturated enzyme (unaffected because the inhibitor is reversible and substrate wins at high concentration). This explains the clinical utility of competitive inhibitors: their effectiveness depends predictably on the ratio of substrate to inhibitor concentration.