C1.1

• Enzymes


  Organic catalysts
• Metabolism


  All the chemical reactions within an organism
• Anabolism


  Energy is used to build simple organic molecules into complex organic molecules
• Catabolism


  Energy is used to break down complex organic molecules into simple organic molecules
• Anabolic reactions


  • Condensation reaction so releases water
  • Requires energy input
  • Examples: Photosynthesis, glycogen formation, protein synthesis
• Catabolic reactions


  • Break down macromolecules into monomers by hydrolysis (uses water)
  • Releases energy when it occurs
  • Example: Digestion
• Functions of ATP


  • Supplying energy to synthesize macromolecules
  • Supplying energy for mechanical motion (muscle movement)
  • Providing energy for the movement of substances across a sodium potassium pump
• Globular proteins


  Have a very specific shape that matches the shape of the enzyme's substrate
• Active site


  The area in which the enzyme matches the enzyme's substrate. If denatured, the function will be lost.
• Induced-fit model (lock and key)


  Represents the enzyme's active site, key represents the substrate
• When the enzyme and the substrate interacts with one another, it would change the shape of the enzyme and the substrate</b>

  
• The changes in the substrate causes stress on its chemical bonds and the bonds become destabilized, favoring reaction
• Activation Energy


  The energy required to destabilize the existing bonds in a substrate so that a reaction can take place
• Activation Energy


  • Substrates that present with larger amounts of activation energy tends to proceed more slowly than the substrates with lower amounts due to the energy barrier as fewer molecules collides with sufficient energy to overcome the initial
• Ways to overcome the energy barrier


  1. Increasing the energy of reacting molecules, thus increasing the rate of collisions with the addition of heat

  2. Lowering the activation energy that is required to stress particular chemical bonds in reactants so that the bonds are broken more easily
• Reactions proceed till there is an established equilibrium between reactants and products
• Enzyme action


  E + S ⇌ ES → EP
• Mechanism of enzyme action


  1. Surface of substrate makes contact with the active site of the enzyme

  2. The enzyme and substrate change shape to provide a fit

  3. A temporary complex called the enzyme-substrate complex is formed

  4. Activation energy (energy required to change the bonds) is lowered, and the substrate is altered by transformation

  5. The transformed substrate, the product is released from active site

  6. Unchanged enzyme combines with other substrate molecules to repeat the process

  
• Effect of temperature on enzymes


  • When the enzyme reaches its upper limit temperature, it starts to lose its 3D shape because the intermolecular bonds are being stressed and broken. This is called DENATURATION.

  
• Effect of pH on enzymes


  • Active site contains a few amino acids charged either positively or negatively. H+ ions (more acidic) and OH- ions (more basic) can change the pH of the enzyme, making it less efficient and causing the bonds to break, making the enzyme lose its shape. Enzymes in humans are usually neutral.

  
• Effect of substrate concentration on enzymes


  • If concentration of reactant molecules increase, more molecules will react and collide with each other, with a greater energy (vice versa for smaller concentrations)

  
• The measurement of any enzyme-catalyzed reaction is by for example measuring the rate at which glucose is produced
• Intracellular and extracellular reactions


  • Intracellular reactions: Enzymes within the cell, e.g. Glycolysis and the Krebs cycle
  • Extracellular Reactions: Enzymes outside of a cell, e.g. Chemical digestion within the gut/digestive system
• Multienzyme complexes


  A group of enzymes work together
• Metabolic efficiency is not 100% - 35% is available for organism's cellular activity, and remaining is transferred as heat, which is very efficient for endotherms to survive temperatures that they can tolerate.
• Linear metabolic pathways


  Ends with a product that is different from the initial reactant/substrate, e.g. Glycolysis starts with one 6-carbon compound, and ends with two 3-carbon compounds
• Cyclic metabolic pathways


  Begins and ends with the same substance, e.g. Krebs cycle begins with 4-carbon compound and ends with the same
• Non-competitive inhibition


  Involves an inhibitor that does not compete for active site, it rather interacts with another site on the enzyme. It causes a change in the active site making it non-functional. Metallic ions are an example of non-competitive inhibitors.
• Allosteric site


  The site on the enzyme where the inhibitor binds, which is not the active site.
• Competitive inhibition


  A molecule competes with a substrate for the active site. When the competitive inhibitor occupies the active site, the rate of chemical change decreases.
• Competitive inhibition


  • Is affected by substrate concentration and can be overcome by the substrate concentration being significantly larger than the inhibitor. More substrate molecules bind to the active site, and chemical reactions may proceed rapidly.

  
• Statins


  • Competitive inhibitors that occupy the active site of an enzyme responsible for the biosynthesis of cholesterol in the liver, lowering the risk of cardiovascular disease.
• Feedback inhibition


  Prevents the cell from wasting chemical resources and energy by making more of a substance than the actual requirement. When in high concentrations, the end product binds with the allosteric site of first enzyme, bringing inhibition → reactivating the enzyme ⟶ allosteric enzyme
• Isoleucine in feedback inhibition


  • Plants and bacteria synthesize this amino acid by using feedback inhibition. The pathway is inactive when large amounts of isoleucine is present, as isoleucine combines with the allosteric site of threonine deaminase, the first enzyme. The active site then is altered and can no longer combine with initial substrate threonine. When isoleucine concentration is low, threonine deaminase can combine with threonine, allow the pathway to proceed.

  
• Penicillin by Dorothy Hodgkin provided the structure of penicillin allowing the greater production levels for the infection-treating medicine
• Mechanism based inhibition


  Penicillin and antibiotics inhibit an enzyme called transpeptidase which catalyses the formation of bacterial cell walls. When used as an irreversible inhibitor, it inactivates the transpeptidase by bonding to a chemical group at active site. The defective cell wall prevents the bacterial reproduction and causes death of bacterial cells. Human cells are not affected as we do not have a cell wall.