Enzymes: Biological Catalysts

• Enzymes are biological catalysts accelerating chemical reactions in living organisms, essential for life-sustaining metabolic processes.
• Enzymes are highly specific, efficient, and regulated, making them indispensable for cellular function.
• Enzymes are typically proteinaceous molecules, with some exceptions like RNA-based ribozymes.
• Enzymes catalyze biochemical reactions by reducing the activation energy required.
• Enzymes are not consumed in reactions, allowing them to be reused multiple times.
• Enzymes exhibit high specificity for substrates.
• Enzymes accelerate reactions without altering the equilibrium.
• Enzyme activity is regulated by environmental conditions and cellular signals.
• Enzymes weaken bonds to lower activation energy, facilitating reactions.
• The substance an enzyme acts on is called the substrate.
• The active site is a restricted region of an enzyme molecule that binds to the substrate.

Lock and Key Hypothesis

• The fit between the substrate and the enzyme's active site is exact, like a key fitting into a lock.
• A temporary enzyme-substrate complex is formed.
• Products released from the active site have a different shape than the substrate.
• The active site is then moulded into a precise conformation.
• The chemical environment is made suitable for the reaction
• Substrate bonds are stretched to facilitate the reaction by lowering the activation energy
• This can explain enzyme specificity and activity loss when enzymes denature.

Induced Fit Hypothesis

• A change in the shape of an enzyme's active site is induced by the substrate binding.
• The change involves alterations in the configuration of the active site.
• This explains how enzymes react with a variety of similar substrates.

Classes of Enzymes

• Enzymes are classified into six major classes based on reaction type.
• This classification follows the International Union of Biochemistry and Molecular Biology (IUBMB) standards.

Oxidoreductases

• Catalyze oxidation-reduction reactions via electron/hydrogen atom transfer
• Examples include:
  • Dehydrogenases (e.g., lactate dehydrogenase)
  • Oxidases (e.g., cytochrome c oxidase)

Transferases

• Transfer functional groups (e.g., methyl, phosphate) from one molecule to another
• Examples include:
  • Kinases (e.g., hexokinase)
  • Transaminases (e.g., alanine aminotransferase)

Hydrolases

• Catalyze hydrolysis reactions using water to break bonds
• Examples include:
  • Lipases (break down lipids)
  • Proteases (break down proteins)

Lyases

• Catalyze the removal or addition of groups to double bonds without hydrolysis or oxidation
• Examples include:
  • Decarboxylases (e.g., pyruvate decarboxylase)
  • Dehydratases (e.g., fumarase)

Isomerases

• Catalyze the rearrangement of atoms within a molecule (isomerization)
• Examples include:
  • Racemases (convert L- to D-isomers)
  • Epimerases (e.g., phosphoglucomutase)

Ligases (Synthetases)

• Catalyze the joining of two molecules, often coupled with ATP hydrolysis
• Examples include:
  • DNA ligase (joins DNA strands)
  • Synthetases (e.g., aminoacyl-tRNA synthetase)

General Properties of Enzymes

Catalytic Efficiency

• Enzymes significantly increase reaction rates by up to 10^17 times faster than uncatalyzed reactions

Specificity

• Enzymes are highly specific for their substrates due to the active site's precise structure.

Types of Specificity

• Absolute: Acts on only one substrate (e.g., urease acts only on urea).
• Group: Acts on a group of related substrates (e.g., hexokinase acts on hexose sugars).
• Bond: Acts on a specific type of bond (e.g., peptidases cleave peptide bonds).

Regulation

• Enzyme activity is tightly regulated by allosteric regulation
• Allosteric regulation involves the binding of effectors at allosteric sites.
• Covalent modification, such as phosphorylation and glycosylation, are ways that enzyme activity is tightly regulated
• Feedback inhibition means reactions are regulated because End products inhibit earlier enzymes in a pathway.

Temperature and pH Sensitivity

• Enzymes have optimal temperature and pH ranges.
• Deviations can lead to denaturation or reduced activity.

Cofactors and Coenzymes

• Many enzymes require non-protein molecules for activity
• Cofactors include inorganic ions (e.g., Mg2+, Zn2+).
• Coenzymes are organic molecules (e.g., NAD+, FAD).

Functions of Enzymes

Metabolism

• Enzymes drive catabolic (breakdown) and anabolic (synthesis) pathways
• Examples include:
  • Glycolysis (breakdown of glucose)
  • DNA polymerase (DNA synthesis)

Digestion

• Digestive enzymes break down food into absorbable nutrients
• Examples include:
  • Amylase (breaks down carbohydrates)
  • Pepsin (breaks down proteins)

Cellular Signaling

• Enzymes regulate signal transduction pathways
• Examples include:
  • Kinases (phosphorylate proteins)
  • Phosphatases (dephosphorylate proteins)

Detoxification

• Enzymes neutralize toxins and drugs
• Examples include:
  • Cytochrome P450 (metabolizes drugs in the liver)
  • Catalase (breaks down hydrogen peroxide)

Immune Response

• Enzymes play roles in immune defense mechanisms
• Examples include:
  • Lysozyme (breaks bacterial cell walls)
  • Proteases in antigen processing

DNA Replication and Repair

• Enzymes ensure accurate DNA replication and repair
• Examples include:
  • DNA polymerase (synthesizes DNA)
  • DNA ligase (repairs DNA breaks)