Enzymes speed up cellular reactions, but their rates can be reduced by inhibitors. Competitive and noncompetitive inhibition alter catalysis in distinct ways, helping explain regulation, toxicity, and how many medicines work.

Core idea: inhibitors reduce enzyme activity

What an inhibitor does

Inhibition changes how readily enzyme–substrate complexes form and how efficiently the enzyme converts substrate to product, without changing the reaction’s overall free-energy change.

Key enzyme regions involved

• Active site: where substrate binds and catalysis occurs; binding depends on shape and chemical compatibility.

• Allosteric site: a separate binding site that can change active-site shape or dynamics when occupied.

Allosteric regulators bind at a site distinct from the active site and change enzyme conformation. In the inhibition panel, allosteric binding alters active-site shape so substrate binding and/or catalysis is reduced, illustrating the structural basis of noncompetitive (allosteric) inhibition. Source

Competitive inhibition

Where it binds and what it competes with

Competitive inhibitors bind the active site, so they directly compete with the substrate for occupancy. This tends to work best when inhibitor structure or charge resembles the substrate enough to fit the active site.

Effects on reaction rate (AP-level interpretation)

• At a given substrate concentration, reaction rate decreases because fewer active sites are available for substrate binding.

• Increasing substrate concentration can reduce the inhibitor’s impact by making substrate binding more likely than inhibitor binding.

• Maximum possible rate can still be reached if enough substrate is present.

Kinetic consequences (conceptual)

• Apparent $K_m$ increases: more substrate is needed to achieve half-maximal rate because binding is being competed away.

• $V_{max}$ unchanged: with sufficient substrate, the enzyme can still achieve the same maximum rate.

Noncompetitive inhibition

Where it binds and how it changes the enzyme

Noncompetitive inhibitors bind an allosteric site, not the active site. Binding shifts enzyme conformation or flexibility so that:

• the active site’s shape/chemistry becomes less effective at binding substrate, and/or

• catalysis becomes less efficient even if the substrate can still bind.

Effects on reaction rate (AP-level interpretation)

• Adding more substrate does not fully overcome inhibition, because the inhibitor is not competing for the same binding site.

• The proportion of enzyme molecules rendered less active depends on inhibitor concentration and affinity for the allosteric site.

Kinetic consequences (conceptual)

• $V_{max}$ decreases: the effective concentration of functional enzyme is lowered.

• $K_m$ often unchanged in the idealised “pure” noncompetitive model because substrate binding affinity may be similar; however, some real enzymes show mixed behaviour.

Connecting inhibition to enzyme-rate models (when graphs are used)

The Michaelis–Menten framework helps describe how inhibitors shift enzyme performance as substrate concentration changes.

Lineweaver–Burk (double-reciprocal) plots highlight inhibition patterns by comparing intercepts and slopes. Competitive inhibition keeps the same y-intercept ($1/V_{max}$) but changes the x-intercept ($-1/K_m$), while pure noncompetitive inhibition raises the y-intercept (lower $V_{max}$) with an unchanged x-intercept. Source

Inhibitors change the observed relationship between $v$ and $[S]$ by altering substrate binding competition (competitive) or by lowering the fraction of active enzyme (noncompetitive).

Michaelis–Menten curves show how inhibitors change reaction velocity as substrate concentration increases. Competitive inhibition shifts the curve rightward (higher apparent $K_m$) while preserving $V_{max}$, whereas noncompetitive inhibition lowers $V_{max}$ (reduced maximal velocity) with minimal change in $K_m$. Source

How to distinguish competitive vs noncompetitive (experimental logic)

Using substrate changes

• If raising substrate concentration substantially restores rate, inhibition is consistent with competitive binding at the active site.

• If rate remains depressed even at high substrate concentration, inhibition is consistent with noncompetitive allosteric action.

Using enzyme concentration changes

• Increasing enzyme concentration can increase overall rate in either case, but noncompetitive inhibition may still cap achievable performance per enzyme molecule because $V_{max}$ per functional enzyme population is reduced.