Enzyme

• Like a catalyst, they increase the rate of biological reactions (10⁶ to 10¹² times faster). But, they are not changed at the end of the reaction.

• They are made of proteins.

• Lower the activation energy for the reaction.

• Less energy is required to convert reactants to products.

• Most of enzymes are globular proteins (water soluble).

• Proteins are not the only biological catalysts.

• Most of enzymes are specific. (Trypsin: cleaves the peptide bonds of proteins) 

• Some enzymes are localized according to need.  (digestive enzymes: stomach)

Names of Enzymes

•  By replacing the end of the name of reaction or reacting compound with the suffix  « -ase ». 

  • Oxidoreductases: oxidation-reduction reactions (oxidase-reductase).

  • Transferases: transfer a group between two compounds.

  • Hydrolases: hydrolysis reactions.

  • Lyases: add or remove groups involving a double bond without hydrolysis.

  • Isomerases: rearrange atoms in a molecule to form a isomer.

  • Ligases: form bonds between molecules.

• Substrate: the compound or compounds whose reaction an enzyme catalyzes.

• Active site: the specific portion of the enzyme to which a substrate binds during reaction.

Enzyme Catalyzed Reaction

An enzyme catalyzes a reaction by,

• Attaching to a substrate at the active site (by side chain (R) attractions).

• Forming an Enzyme-Substrate Complex (ES).

• Forming and releasing products.

• E + S ---- ES ---- E + P

Lock and Key Model

•  Enzyme has a rigid, nonflexible shape.

•  An enzyme binds only substrates that exactly fit the active site.

• The enzyme is analogous to a lock.

• The substrate is the key that fits into the lock

Induced Fit Model

• Enzyme structure is flexible, not rigid.

• Enzyme and substrate adjust the shape of the active site to bind substrate.

• The range of substrate specificity increases.

• A different substrate could not induce these structural changes and no catalysis would occur.

Factors affecting enzyme activity

Activity of enzyme: how fast an enzyme catalyzes the reaction.

1. Temperature

2. pH

3. Substrate concentration

4. enzyme concentration

5. Enzyme inhibition

Temperature

•  Enzymes are very sensitive to temperature.

•  At low T, enzyme shows little activity (not an enough amount of energy for the catalyzed reaction). 

• At very high T, enzyme is destroyed (tertiary structure is denatured).

• Optimum temperature: 37°C or body temperature.

pH

•  Optimum pH: is 7.4 in our body.

•  Lower or higher pH can change the shape of enzyme. (active site change and substrate cannot fit in it)

•  But optimum pH in stomach is 2.

• Stomach enzyme (Pepsin) needs an acidic pH to digest the food.

• Some damages of enzyme are reversible.

Substrate and enzyme concentration

Enzyme Concentration ^ - Rate of Reaction ^

Substrate Concentration ^ -

First: Rate of Reaction ^

End: Rate of reaction reaches to its maximum: all of the enzymes are combined with substrates.

Enzymes inhibition

Inhibitors cause enzymes to lose catalytic activity.

1. Competitive inhibitor

2. Noncompetitive inhibitor

Competitive Inhibitor

•  Inhibitor has a structure that is so similar to the substrate.

•  It competes for the active site on the enzyme.

•  Solution: increasing the substrate concentration.

Noncompetitive Inhibitor

•  Inhibitor is not similar to the substrate.

•  It does not compete for the active site.

•  When it is bonded to enzyme, change the shape of enzyme (active site) and substrate cannot fit in the active site (change tertiary structure).

•  Like heavy metal ions (Pb²⁺, Ag⁺, or Hg²⁺) that bond with –COO^-, or –OH groups of amino acid in an enzyme.

•  Penicillin inhibits an enzyme needed for formation of cell walls in bacteria: infection is stopped.

•  Solution: some chemical reagent can remove the inhibitors. 

Competitive and Noncompetitive Inhibitor

Enzyme cofactors

Metal ions:

• bond to side chains

  • obtain from foods.

  • Fe²⁺ and Cu²⁺ are gain or loss electrons in redox reactions.

  • Zn²⁺ stabilize amino acid side chain during reactions. 

• Enzyme and cofactors work together.

• Catalyze reactions properly.

Vitamins and Coenzymes

• Vitamins are organic molecules that must be obtained from the diet. (our body cannot make them)

• Water-soluble vitamins: have a polar group (-OH, -COOH, or …)

  • They are not stored in the body (must be taken).

  • They can be easily destroyed by heat, oxygen, and ultraviolet light (need care).

• Fat-soluble vitamins: have a nonpolar group (alkyl, aromatic, or …)

  • They are stored in the body (taking too much = toxic).

  •  A, D, E, and K are not coenzymes, but they are important: vision, formation of bone, proper blood clotting.

Zymogens (Proenzymes)

Inactive enzyme that becomes an active

enzyme after a chemical change (remove or change some polypeptides).

Trypsinogen (inactive enzyme – Pancreas) 🡪Trypsin (active enzyme – Small Intestine)

Digestive enzyme (hydrolyzes the peptide bonds of proteins)

Enzymes in medicine

Most of enzymes are in cells.

•  Small amounts of them are in body fluids (blood, urine,…).

• Level of enzyme activity can be monitored.

• Certain enzymes are present in higher amounts in particular cells.

• If these cells are damaged or die, the enzymes are released into the bloodstream and can be detected.

Inhibitors can be useful drugs.

• Penicillin inhibits the enzyme that forms cell walls of bacteria, destroying the bacterium.

• ACE (angiotensin-converting enzyme) causes blood vessels to narrow, increasing blood pressure.

• ACE inhibitors are given to those with high blood pressure to prevent ACE’s synthesis from its zymogen.

• HIV protease is an essential enzyme that allows the virus to make copies of itself.

• HIV protease inhibitors interfere with this copying, decreasing the virus population in the patient.