Competitive Inhibition

Competitive inhibition occurs when an inhibitor and the substrate compete for the same binding site on an enzyme, so that only one can occupy the active site at a time. Because more substrate can outcompete the inhibitor, competitive inhibition raises the apparent Km while leaving the maximal velocity Vmax unchanged.

Definition

Competitive inhibition is a form of reversible inhibition in which the inhibitor binds the free enzyme at or near the active site in mutual exclusion with the substrate, increasing the apparent Km without altering Vmax.

Scope

The entry covers the binding logic of competitive inhibitors, their characteristic effect on Michaelis-Menten parameters, the inhibition constant Ki, and how competitive inhibition is distinguished from other reversible types. It is a methodological and biochemical reference, not clinical guidance.

Core questions

• Does increasing substrate concentration overcome the inhibition?
• Is Vmax preserved while the apparent Km rises?
• Where does the inhibitor bind relative to the substrate site?

Key concepts

• Mutual exclusion of inhibitor and substrate
• Unchanged Vmax, increased apparent Km
• Inhibition constant (Ki)
• Surmountability by excess substrate
• Lineweaver-Burk lines intersecting on the 1/v axis

Key theories

Mutual-exclusion binding model

Competitive inhibition is modelled by the inhibitor and substrate binding the free enzyme in mutually exclusive fashion; the steady-state treatment predicts an unchanged Vmax and an apparent Km scaled by the factor (1 + [I]/Ki).

Mechanisms

A competitive inhibitor binds the free enzyme, typically at or overlapping the active site, preventing substrate binding while it is bound. Because binding is reversible and mutually exclusive, raising substrate concentration shifts the equilibrium toward the enzyme-substrate complex and can fully overcome inhibition; hence Vmax is unchanged while the apparent Km increases by the factor (1 + [I]/Ki) (Goldstein, 1944; Cornish-Bowden, 2012). On a double-reciprocal (Lineweaver-Burk) plot the lines for different inhibitor concentrations intersect on the 1/v axis. For competitive inhibitors the Cheng-Prusoff relationship links the measured IC50 to Ki and substrate concentration (Cheng & Prusoff, 1973).

Clinical relevance

Many drugs are competitive inhibitors that resemble the natural substrate and compete for the active site; understanding surmountability helps explain why their effect can depend on substrate or co-factor levels (Copeland, 2013). This entry describes the mechanism for reference and education and does not give dosing or treatment advice.

History

The kinetic distinction of competitive inhibition from other reversible types was formalised within the steady-state framework of enzyme kinetics by the 1940s (Goldstein, 1944), and the relationship between the experimentally convenient IC50 and the intrinsic constant Ki for competitive inhibitors was set out by Cheng and Prusoff in 1973 (Cheng & Prusoff, 1973).

Key figures

• Avram Goldstein
• Athel Cornish-Bowden
• Yung-Chi Cheng
• William Prusoff

Seminal works

• goldstein-1944
• cheng-prusoff-1973

Frequently asked questions

How can you tell an inhibitor is competitive?

Adding more substrate overcomes the inhibition, the maximal velocity Vmax is unchanged, and the apparent Km rises; on a double-reciprocal plot the lines for different inhibitor levels meet on the 1/v axis.

Why does Vmax stay the same in competitive inhibition?

Because at very high substrate concentrations the substrate outcompetes the inhibitor for the active site, so the enzyme can still reach its full maximal rate.