Enzymes

• Enzymes


  Complex catalysts that control reactions in the body
• Enzymes


  • Work in aqueous solution
  • Must work efficiently and in excellent yields
  • Must be reliable
• Catalysts


  Speed up the rate of a reaction without being consumed itself during the reaction
• Enzymes


  Special types of proteins
• How enzymes work


  1. Bind the substrate(s)

  2. Bind other molecules (cofactors) which help with the reaction

  3. Do the reaction

  4. Release the product

  
• An enzyme will only catalyse a certain type of reaction using certain substrates

  
• Example of an enzyme

  • Carbonic anhydrase enzyme speeds up the reaction of carbon dioxide with water by over 1 million times
• Most enzymes have "ase" at the end of their name
• Active site


  Where the recognition and catalytic abilities of enzymes come about through specific interactions with functional groups

  
• Esterase enzymes


  • Found in the bloodstream and throughout the body
  • Hydrolyse any drug containing an ester which enters the bloodstream
• Pro-drugs


  Often activated by esterases - dosed as an ester, the esterase would then hydrolyse the drug and it would become the active form
• How esterase enzymes work


  1. Bind the substrate and a molecule of water

  2. Acidic and basic groups in the active site catalyse the reaction

  3. Reaction occurs in a concerted manner, confined to the active site

  
• In a lab, the ester hydrolysis reaction would need to be heated to get it to go, whereas the enzyme-catalysed reaction occurs at body temperature in a highly effective and concerted manner
• Metalloenzymes


  Enzymes that contain tightly bound metal ions (usually from the transition block) which can bind substrates in specific orientations, carry out redox reactions, and stabilise negative charges
• Carbonic anhydrase


  • A metalloenzyme with Zn2+ tetrahedrally coordinated to 3 histidine residues and a water
• Enzymes and drugs


  • Enzymes bring about drug metabolism
  • Enzymes activate pro-drugs
  • Enzymes can themselves be drug targets
  • Some disease states arise through the malfunctioning of an enzyme
• Enzyme inhibitors


  Molecules that can bind in the enzyme and prevent substrates or cofactors from binding, preventing the normal catalysed reaction

  
• Reversible inhibitors


  Bind in the active site in a similar way to the substrate, competing with the substrate for binding

  
• Irreversible inhibitors


  Bind to the enzyme permanently, e.g. by forming covalent bonds, so the inhibition cannot be overcome by increasing substrate concentration

  
• Competitive inhibition


  Substrate and inhibitor molecules compete for the same binding site
• Non-competitive inhibition


  Inhibitor binds at an allosteric site, changing the shape of the active site and preventing substrate binding, without directly competing with the substrate

  
• Aspirin


  • A pro-drug for salicylic acid, which inhibits the enzyme cyclooxygenase (COX) to alleviate pain and inflammation by reducing prostaglandin production