3.2.1 Models of Enzyme Action

The mechanism of enzyme action can be explained with the help of two different models:

1. Lock and Key Model (Fischer's Model, 1894)

Definition: Emil Fischer proposed the Lock and Key model in 1894. According to this model, the enzyme is a lock and the substrate is a key.

Key Points:

• As the key has a similar shape to that of the keyhole of the lock, in the same manner, the substrate has a similar shape to the active site of the enzyme.
• The substrate binds tightly to the active site of the enzyme, just like the key into its lock.
• If the shape of the substrate and active site are not similar, the substrate will not be able to bind to the enzyme.
• An enzyme is a rigid structure and the shape of the active site will not change or modify during the binding process.
• In some books and diagrams, you may find the reverse, i.e., key as the enzyme and lock as the substrate.

• The notched portion of the key is equivalent to the active site on the enzyme.
• It reflects that enzymes are highly specific in their action and each enzyme can carry out only one particular reaction.

• The enzymes which work according to this model are called non-regulatory enzymes.
• However, this model is exercised by a very small number of enzymes.
• Examples: Sucrase, Maltase

• It assumes that the active site is rigid.
• It does not explain how enzymes can catalyze reactions with related substrates.
• It does not explain the flexibility of enzymes.

2. Induced Fit Model (Koshland's Model, 1959)

Definition: Koshland proposed the Induced Fit model in 1959. According to this model, the active site is flexible; therefore, it is modified as the substrate interacts with the enzyme.

Key Points:

• The amino acids which make up the active site are molded into a precise shape which enables the enzyme to perform its catalytic function more effectively.
• The change which is induced in the shape of the active site is responsible for the conversion of substrate into product.
• As the reaction is completed, the active site regains its original shape.
• This is the flexibility of active site which allows more than one type of related substrates to be attached on active site.
• Therefore, an enzyme can carry out more than one type of related reactions.

Example: - Carbonic anhydrase can add O₂ to haemoglobin as well as can control the formation of carbonic acid and bicarbonate in blood.

• Enzymes which follow the induced fit mechanism are called regulatory or allosteric enzymes.
• Example: Hexokinase

• It explains the flexibility of enzymes.
• It explains how enzymes can catalyze reactions with related substrates.
• It explains how enzymes can carry out more than one type of related reactions.

Comparison of Lock and Key Model and Induced Fit Model

Enzyme Specificity

Definition: Enzyme specificity is the ability of an enzyme to catalyze only one particular reaction or a group of closely related reactions.

Types of Specificity:

• Example: Urease acts only on urea.
• Equation: Urea + Water → (Urease) → Ammonia + Carbon dioxide

2. Relative specificity: One enzyme catalyzes a group of related substrates. - Example: Lipases act on different lipids.

3. Stereochemical specificity: Enzyme acts on only one stereoisomer. - Example: D-amino acid oxidase acts only on D-amino acids.

Example of Enzyme Action

Urease: Urea + Water Urease→ Ammonia + Carbon dioxide

Carbonic Anhydrase: Hb + 4O₂ Carbonic anhydrase→ HbO₂ (Oxyhaemoglobin) CO₂ + H₂O Carbonic anhydrase→ H₂CO₃ H₂CO₃ Carbonic anhydrase→ H⁺ + HCO₃^-

Intermediate Level

Enzyme Action in Detail

Lock and Key Model in Detail

Induced Fit Model in Detail

Enzyme Specificity in Detail

Important Points

• 1. The substrate first binds to the active site of the enzyme to form an enzyme-substrate (ES) complex.
• 2. Then the substrate is converted into product while it is attached to the enzyme (EP complex).
• 3. Finally, the product is released, thus allowing the enzyme to start all over again.
• E + Senzyme + substrate ⇌ ESenzyme-substrate complex ⇌ EPenzyme-product complex → E + Penzyme + product
• 4. 3.2.1 Models of Enzyme Action:
• - The mechanism of enzyme action can be explained with the help of two different models.
• 5. Lock and Key Model:
• - Emil Fischer proposed Lock and key model (in 1894).
• - According to this model, the enzyme is a lock and the substrate is a key.
• - As the key has a similar shape to that of the keyhole of the lock, in the same manner, the substrate has a similar shape to the active site of the enzyme.
• - The substrate binds tightly to the active site of the enzyme, just like the key into its lock.
• - If the shape of the substrate and active site are not similar, the substrate will not be able to bind to the enzyme.
• - An enzyme is a rigid structure and the shape of the active site will not change or modify during the binding process.
• - In some books and diagrams you may find the reverse i.e., key as the enzyme and lock as the substrate.
• - Actually, the notched portion of the key is equivalent to the active site on the enzyme.
• - It reflects that enzymes are highly specific in their action and each enzyme can carry out only one particular reaction.
• - The enzymes, which work according to this model, are called non-regulatory enzymes.
• - However, this model is exercised by a very small number of enzymes, for example sucrase, maltase etc.
• - The ability of enzyme to catalyze one specific reaction is perhaps its most significant property.
• - Although, many enzymes show a broad range of specificity towards the substrate they catalyze.
• - When one enzyme can catalyze only one substrate and essentially no others it is called absolute specificity e.g., urease.
• - Equation: Urea + Water → (Urease) → Ammonia + Carbon dioxide
• 6. Induced Fit Model:
• - Koshland proposed Induced fit model (in 1959).
• - According to this model the active site is flexible; therefore, it is modified as the substrate interacts with enzyme.
• - The amino acids, which makeup the active site are molded into a precise shape which enables the enzyme to perform its catalytic function more effectively.
• - The change which is induced in the shape of active site is responsible for the conversion of substrate into product.
• - As the reaction is completed the active site regains its original shape.
• - This is the flexibility of active site which allows more than one type of related substrates to be attached on active site and therefore, an enzyme can carry out more than one type of related reactions.
• - The example is carbonic anhydrase which can add O₂ to haemoglobin as well as can control the formation of carbonic acid and bicarbonate in blood.
• - Enzymes, which follow the induced fit mechanism, are called regulatory or allosteric enzymes for example hexokinase.

Remember

• - Enzyme action: E + S → ES → EP → E + P
• - Lock and Key Model: Fischer (1894); rigid active site; substrate fits exactly
• - Induced Fit Model: Koshland (1959); flexible active site; substrate induces a change
• - Lock and Key: Non-regulatory enzymes (e.g., sucrase, maltase)
• - Induced Fit: Regulatory or allosteric enzymes (e.g., hexokinase, carbonic anhydrase)
• - Absolute specificity: One enzyme, one substrate (e.g., urease)
• - Relative specificity: One enzyme, related substrates (e.g., lipases)
• - Stereochemical specificity: One enzyme, one stereoisomer (e.g., D-amino acid oxidase)

Common Mistakes

• 1. Confusing Lock and Key and Induced Fit models – Lock and Key = rigid; Induced Fit = flexible.
• 2. Thinking the active site is always rigid – The active site is flexible in the Induced Fit model.
• 3. Forgetting the scientists who proposed the models – Fischer (Lock and Key, 1894); Koshland (Induced Fit, 1959).
• 4. Confusing absolute and relative specificity – Absolute = one substrate; Relative = related substrates.
• 5. Thinking all enzymes follow the Lock and Key model – Only a small number of enzymes follow this model.
• 6. Forgetting the examples – Sucrase, Maltase (Lock and Key); Hexokinase, Carbonic anhydrase (Induced Fit).
• 7. Thinking enzymes are consumed in the reaction – Enzymes are not consumed; they are reused.
• 8. Confusing ES and EP complexes – ES = enzyme-substrate complex; EP = enzyme-product complex.
• 9. Thinking the enzyme changes permanently – The enzyme regains its original shape after the reaction.
• 10. Forgetting the role of activation energy – Enzymes lower the activation energy of the reaction.
• 11. Thinking all enzymes have the same specificity – Different enzymes have different specificities (absolute, relative, stereochemical).
• 12. Confusing the lock and key roles – Enzyme = lock; Substrate = key (or vice versa in some books).

Quick Revision

• The substrate first binds to the active site of the enzyme to form an enzyme-substrate (ES) complex.
• Then the substrate is converted into product while it is attached to the enzyme (EP complex).
• Finally, the product is released, thus allowing the enzyme to start all over again.
• E + S → ES → EP → E + P
• The mechanism of enzyme action can be explained with the help of two different models.
• Lock and Key Model:
• Emil Fischer proposed Lock and key model (in 1894).
• According to this model, the enzyme is a lock and the substrate is a key.
• As the key has a similar shape to that of the keyhole of the lock, in the same manner, the substrate has a similar shape to the active site of the enzyme.
• The substrate binds tightly to the active site of the enzyme, just like the key into its lock.
• If the shape of the substrate and active site are not similar, the substrate will not be able to bind to the enzyme.
• An enzyme is a rigid structure and the shape of the active site will not change or modify during the binding process.
• In some books and diagrams you may find the reverse i.e., key as the enzyme and lock as the substrate.
• Actually, the notched portion of the key is equivalent to the active site on the enzyme.
• It reflects that enzymes are highly specific in their action and each enzyme can carry out only one particular reaction.
• The enzymes, which work according to this model, are called non-regulatory enzymes.
• However, this model is exercised by a very small number of enzymes, for example sucrase, maltase etc.
• When one enzyme can catalyze only one substrate and essentially no others it is called absolute specificity e.g., urease.
• Equation: Urea + Water → (Urease) → Ammonia + Carbon dioxide
• Induced Fit Model:
• Koshland proposed Induced fit model (in 1959).
• According to this model the active site is flexible; therefore, it is modified as the substrate interacts with enzyme.
• The amino acids, which makeup the active site are molded into a precise shape which enables the enzyme to perform its catalytic function more effectively.
• The change which is induced in the shape of active site is responsible for the conversion of substrate into product.
• As the reaction is completed the active site regains its original shape.
• This is the flexibility of active site which allows more than one type of related substrates to be attached on active site and therefore, an enzyme can carry out more than one type of related reactions.
• The example is carbonic anhydrase which can add O₂ to haemoglobin as well as can control the formation of carbonic acid and bicarbonate in blood.
• Enzymes, which follow the induced fit mechanism, are called regulatory or allosteric enzymes for example hexokinase.

60-Second Revision

• Enzyme action: E + S → ES → EP → E + P
• Lock and Key Model: Fischer (1894); rigid active site; substrate fits exactly
• Induced Fit Model: Koshland (1959); flexible active site; substrate induces a change
• Lock and Key: Non-regulatory enzymes (e.g., sucrase, maltase)
• Induced Fit: Regulatory or allosteric enzymes (e.g., hexokinase, carbonic anhydrase)
• Absolute specificity: One enzyme, one substrate (e.g., urease)
• Relative specificity: One enzyme, related substrates (e.g., lipases)
• Stereochemical specificity: One enzyme, one stereoisomer (e.g., D-amino acid oxidase)
• Warning: Lock and Key model has a rigid active site; Induced Fit model has a flexible active site. Fischer proposed Lock and Key (1894); Koshland proposed Induced Fit (1959). Enzymes are not consumed in the reaction. The enzyme regains its original shape after the reaction. Absolute specificity = one substrate; Relative specificity = related substrates.