Enzymes are Biological catalyst that speeds up the rate of
reaction without undergoing any change by itself.
Reversible inactivation: Inhibitor
forms an unstable, non-covalently bonded, enzyme inhibitor complex. Lost
activity can be regained.
Irreversible inactivation: Inhibitor
forms strong covalent bonds so that it cannot be dislodged. Therefore the
enzyme activity lost forever.
Three major types of
Reversible Inhibition
1. Competitive (Inhibitor binds to Active site)
2. Non Competitive (Inhibitor binds to Allosteric site)
3. Uncompetitive Inhibition (Inhibitor binds to ES complex)
Competitive Inhibition
or Isosteric inhibition
- The inhibitor structural homologue competes with the substrate for the same active site of an enzyme.
- Depends on relative concentration of inhibitor and its affinity
- Binds to free enzyme
- Can be reversed by adding more substrate so that inhibitor is out competed.
Lowering Km; decreases
affinity (increases Km value) and Vmax remains the same;
as Vmax can be achieved by adding more substrate
What is Km of
an enzyme?
Michaelis
constant (Km): The substrate concentration at which the reaction
rate is half of V max
Km value is different for
different enzymes
Km refers to the affinity of
an enzyme for its substrate
Smaller the value higher is
the affinity
Non-Competitive
Inhibition
- The inhibitor binds to allosteric site
- It never blocks E-S formation
- This binding causes conformational change preventing the conversion of E-S complex to E-P complex
- It is not fully reversible inhibition some re-activators to delock non competitive inhibitor
- Km remains same (no change in affinity) & Vmax decreases as many ES complex will not form the product due to inhibitor binding to the allosteric site
- Eg : Heavy metals like Hg++, Pb++, drugs, pesticides, cyanide on cytochrome oxidase – can be removed by using a chelating agent EDTA
Uncompetitive
Inhibition
- The inhibitor binds to E-S complex
- Inhibitor binds to E-S complex and not with free enzyme and facilitates tight E-S binding preventing enzyme action
- Cannot be overcome by increasing substrate concentration
- Decreases Km value (increases affinity) &Vmax
- Eg: Inhibition of placental alkaline phosphatase by phenylalanine