Enzyme Inhibition and Metabolic Control
Competitive inhibition raises apparent Km without lowering Vmax. Pure non-competitive inhibition lowers Vmax without changing Km. Reversible end-product inhibition lets accumulated products reduce their own production.
What a learner can do afterwards
- Predicts how competitive, pure non-competitive and uncompetitive inhibition affect Vmax and apparent Km.
- Explains why separate-site binding alone does not establish pure non-competitive inhibition and why extra substrate does not restore its Vmax.
- Describes reversible end-product inhibition as a feedback control loop.
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Measure initial rates at fixed enzyme concentration, temperature and pH. Hold inhibitor concentration fixed as substrate varies. In reversible competitive inhibition, substrate and inhibitor cannot bind the enzyme together. This can involve the active site or mutually exclusive binding at separate sites. More substrate reduces inhibition: Vmax stays unchanged, while apparent Km rises.
Vmax is the limiting rate at high substrate concentration. Km is the substrate concentration giving half of that curve's Vmax. Suppose the control has Vmax 12 rate units and Km 3 mmol/L. A competitive inhibitor leaves Vmax at 12 but raises apparent Km to 9 mmol/L. Both curves reach 6 rate units at their own Km; the inhibited reaction needs more substrate.
A pure non-competitive inhibitor binds away from the active site with equal affinity to free enzyme and enzyme with substrate bound. Substrate can still bind, but inhibitor-bound enzyme cannot catalyse the reaction. Vmax falls and Km stays unchanged. Extra substrate cannot restore the control Vmax because it does not prevent this inhibitor from binding.
Separate-site binding alone does not prove pure non-competitive inhibition. Pure non-competitive inhibition is a special case of mixed inhibition. Other mixed inhibitors lower Vmax and may raise or lower apparent Km. An uncompetitive inhibitor binds only to the enzyme-substrate complex; Vmax and apparent Km decrease by the same factor.
In end-product inhibition, accumulated product inhibits an earlier regulatory enzyme, often at an allosteric site away from the active site. Production slows. If product use exceeds production, the product pool falls. With reversible binding, less product then remains bound and enzyme activity can recover. This feedback does not require enzyme destruction or a pure non-competitive rate pattern.
ATP and ADP help regulate cellular respiration. High ATP availability can inhibit some regulatory enzymes, reducing further ATP production. A rise in ADP relative to ATP can activate some enzymes and increase respiration. The response depends on the enzyme and other conditions. ATP does not inhibit every enzyme, and ADP does not directly remove every inhibitor.
In competitive inhibition, substrate and inhibitor binding are mutually exclusive. Raising substrate reduces inhibitor occupancy, so the rate approaches the unchanged control Vmax. A pure non-competitive inhibitor can also bind enzyme with substrate bound. Extra substrate cannot prevent its inhibition, so the rate approaches a lower Vmax. Increasing substrate changes the measured rate; it does not raise competitive Vmax.
Competitive inhibition raises apparent Km. Pure non-competitive inhibition lowers Vmax. Reversible product feedback adjusts pathway activity.
Lesson, questions and flashcards written for this dataset. Khan Academy articles on enzyme kinetics and regulation and OpenStax's Regulation of Cellular Respiration were consulted for biological facts.
Readings and flashcards written for this dataset. Khan Academy and OpenStax were consulted for biological facts. The linked video Competitive inhibition is credited to Khan Academy.
More to read
Compare the two rate measurements
An inhibition experiment needs a fair comparison. Measure initial rates at several substrate concentrations while keeping enzyme concentration, temperature and pH the same. Within an inhibited series, keep inhibitor concentration fixed too.
For each series, identify Vmax, the limiting rate at high substrate concentration. Then find the substrate concentration giving half of that series's Vmax. This is Km, or apparent Km when describing an inhibitor's observed effect.
Competitive inhibition leaves Vmax unchanged and raises apparent Km. Pure non-competitive inhibition lowers Vmax without changing Km. Uncompetitive inhibition lowers both by the same factor. Other mixed inhibition can lower Vmax while raising or lowering apparent Km. A lower maximum alone therefore cannot identify pure non-competitive inhibition.
Follow the product pool
A product pool depends on both formation and use. If a pathway forms product faster than the cell uses it, the pool grows. An accumulated product may bind to an earlier regulatory enzyme and slow further formation. This is end-product inhibition.
Slower formation does not by itself mean that the existing pool falls. Product use must exceed formation for that to happen. As the pool falls, reversible inhibitor binding can decrease and the enzyme can recover activity.
The product often binds at an allosteric site, separate from the active site. This location does not establish the precise Vmax and Km pattern. Feedback regulation need not behave like the pure non-competitive model.
Binding and catalysis are different events
A substrate can bind without being converted into product. That distinction helps explain inhibition.
In the active-site model of competitive inhibition, substrate and inhibitor cannot occupy the active site together. Increasing substrate concentration favours substrate occupancy, so the limiting rate can approach the uninhibited Vmax.
In pure non-competitive inhibition, the inhibitor has equal affinity for free enzyme and enzyme with substrate bound. Substrate can bind, but inhibitor-bound enzyme cannot catalyse the reaction. Increasing substrate therefore does not restore the control Vmax.
These reversible models do not require permanent protein damage. Nor must a competitive inhibitor have exactly the substrate's shape: what matters here is their competition for binding.
ATP availability can affect respiration
Cells consume ATP and replenish it through processes including cellular respiration. Regulation helps the replenishment rate respond to changing demand.
ATP can inhibit some regulatory enzymes. When ATP is readily available, this feedback can reduce further ATP production. A rise in ADP relative to ATP can activate some enzymes and favour faster respiration.
The response occurs at particular regulated steps. It does not mean that ATP inhibits every enzyme, or that ADP directly removes every inhibitor. Substrate supply and other conditions also affect the rate.
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