Enzymes: Biological Catalysts

• Enzymes are thermo-labile biological catalysts that remain chemically unchanged during reactions
• Enzymes are proteins and highly specific in their action
• Enzymes are synthesized by living cells but can act intracellularly or extracellularly

Terminology of Enzymes

• Hydrolytic enzymes are named by adding "ase" to the substrate they act upon
  • The substrate being the substance acted upon
  • Example: sucrase, lipase, and lactase
• For other enzymes, the name consists of the substrate, mechanism of action, and "ase"
  • Example: succinate dehydrogenase

Chemical Nature of Enzymes

• All enzymes are proteins and can be either simple or conjugated
• Simple protein enzymes consist of protein only, such as pepsin and maltase
• Conjugated protein enzymes consist of a protein part (apoenzyme) and a non-protein part
  • The whole enzyme is called holoenzyme
  • The non-protein part can be firmly attached (prosthetic group) or loosely attached (coenzyme)
• Coenzymes usually contain vitamin B as part of their structure
  • Examples include:
    • Co I: Nicotinamide adenine dinucleotide (NAD), acts as hydrogen carrier
    • Co II: Nicotinamide adenine dinucleotide phosphate (NADP), acts as hydrogen carrier
    • FMN: Flavin mononucleotide, acts as hydrogen carrier
    • FAD: Flavin adenine dinucleotide, acts as hydrogen carrier

Mechanism of Action of Enzyme

• Enzymes bind to their specific substrate, forming an enzyme-substrate complex
• This binding lowers the activation energy needed to convert the substrate to a product
• The intermediate complex decomposes, yielding the product and releasing the enzyme
• Each enzyme has an active site where it binds to its specific substrate

Classification of Enzymes

• Enzymes are classified into six major classes based on the reaction they catalyze:
  • Oxidoreductases: Catalyze oxidation-reduction reactions between two substrates
    • Oxidases: Use oxygen as an electron acceptor without incorporating it into the substrate
    • Dehydrogenases: Remove hydrogen
    • Oxygenases: Directly incorporate oxygen into the substrate
    • Peroxidases: Use H2O2 as an electron acceptor
  • Transferases: Catalyze the transfer of a group from one substrate to another
    • Methyltransferases
    • Aminotransferases: Transfer NH2 from amino acids to keto acids
    • Kinases: Transfer phosphate from ATP to a substrate or vice versa
    • Phosphorylases: Transfer inorganic phosphate (Pi) to a substrate
  • Hydrolases: Catalyze hydrolysis (breakdown of a chemical bond by addition of water)
    • Phosphatases: Remove (cleave) phosphate from a substrate
    • Esterases: Cleave ester bonds like those in nucleic acids (nucleases) and lipids (lipases)
    • Proteases: Cleave amide bonds such as those in proteins (peptidases)
  • Lyases: Catalyze the removal of a group
  • Decarboxylases: Catalyze the removal of CO2
  • Isomerases: Catalyze the interconversion of one substrate to its isomer
  • Ligases: Catalyze the joining of two substrates using energy

Factors Affecting Enzyme Activity

• Concentration of the substrate: The velocity of enzyme action is directly proportional to the concentration of the substrate
• Concentration of the enzyme: The reaction velocity is directly proportional to the enzyme concentration, up to a certain point
• Effect of temperature: Each enzyme has an optimum temperature at which its action is maximum; activity decreases above or below this temperature
• Effect of pH: Each enzyme has an optimum pH; activity decreases above or below this pH
• Activators: Enzyme activators are inorganic ions; chloride ions activate amylase, and magnesium ions activate kinases

Enzyme Inhibition

• Non-specific inhibitors: Act on all enzymes or a wide variety of enzymes; include agents that precipitate or denature proteins
• Specific inhibitors: Act on one enzyme or a small number of enzymes
  • Competitive inhibitors: Similar in structure to the substrate and compete for the active site
    • Example: Sulfonamide is similar to para-amino benzoic acid and is a bacteriostatic drug
    • Example: Dicumarol is similar to vitamin K and prevents prothrombin synthesis, acting as an in-vivo anticoagulant
  • Non-competitive inhibitors: Not similar to the substrate and don't compete for the active site
    • Allosteric Modifiers: Molecules bind non-covalently at sites other than active sites
    • Feedback Inhibition: The end product of a series of metabolic reactions directly inhibits the first enzyme
    • Feedback Regulation: The end product of a series of metabolic reactions inhibits the gene controlling the synthesis of the first enzyme