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  1. 1. Function & Composition Catalytic Reactions Specificity Rate of Reaction RegulationEnzyme
  2. 2. Topics Function & Composition Catalytic Reaction Enzyme Specificity Factor affecting enzymatic rate of reaction Enzyme Regulation
  3. 3. Enzyme Function Enzyme: biological catalyst that speed up rates of reaction that would otherwise be too slow to support life Catalyst:a chemical agent that changes the rate of a reaction without being consumed by the reaction Enzymes are unaffected by the reaction and are reusable
  4. 4. Enzyme Function Enzymes act on substrates at their active site Substrate: reactant that enzyme acts on Active site: a pocket where the substrate binds; catalytic center where substrate is converted to product
  5. 5. Active Site  R-groups on amino acids of the enzyme interact with the substrate at the active site
  6. 6. Enzyme Composition Almost all enzymes are composed of proteins Exception: ribozyme  RNA that catalyze reactions on other RNA  Hydrolysis at phosphodiester bond
  7. 7. Enzyme Names Most enzymes have an –ase ending The root name suggests what molecule it acts upon Example: ATPase
  8. 8. Catalytic Reactions Chemical reactions between molecules involve both bond breaking and forming. Example: sucrose hydrolysis  bond between glucose and fructose is broken  new bonds formed with H+ and OH-
  9. 9. Exergonic reaction A reaction that releases energy But reaction still needs an initial investment of energy to break bonds in the reactant Energy usually supplied in the form of heat (thermal energy)
  10. 10. Activation Energy (EA) Amount of energy needed to push the reactants over an energy barrier. Reactants absorb energy becoming unstable  Thermal agitation increase speed of molecules and number & strength of collisions  Peak of instability = transition state Eventually bond breaks
  11. 11. Change in Free Energy (ΔG) New bonds release more energy than the initial investment to break bonds. Difference in free energy between products and reactants is the ΔG. ΔG is negative in an exergonic reaction.
  12. 12. Enzymes lower EA Allows transition state to occur at a lower temperature which speeds up the reaction. ΔG is unchanged
  13. 13. Mechanism for Lowering EA1. Proximity & Orientation2. Bond strain3. Microenvironment4. Covalent Catalysis
  14. 14. 1. Proximity & Orientation active site brings reactants closer together and in the correct orientation
  15. 15. 2. Bond strain active site bends bonds in substrate making it easier to break
  16. 16. 3. Microenvironment R-groups at the active site provides a favourable environment for the reaction Eg: acidic amino acids  low pH  proton donorshttp://twistedsifter.com/2010/08/libraries-around-the-world/ Thomas Fisher Rare Book Library. University of Toronto.
  17. 17. 4. Covalent Catalysis Enzymes may bind covalently to substrates in an intermediate step before returning to normal
  18. 18. Enzyme Specificity: Substrate Substrate specific: recognize one specific substrate  can even distinguish between particular configurations (e.g. enantiomers)  exception: racemase (an isomerase) which recognize both enantiomers and will interconvert between the two forms but the reverse is not true: a given substrate may be acted on by a number of different enzymes substrate specificity due to the fit between the active site and the substrate
  19. 19. Induced-Fit Model As the substrate binds, the enzyme changes shape leading to a tighter fit, bringing chemical groups in position to catalyze the reaction. Binding of a substrate induces a favourable change in the shape of the active site
  20. 20. Video: Enzyme SpecificityTutorial Animation http://www.wiley.com//legacy/college/boyer/ 0470003790/animations/enzyme_binding/enz yme_binding.htm
  21. 21. Sequence of events E + S  ES  ES*  EP  E + P1. Substrate binds to available active site pocket forming the enzyme substrate (ES) complex2. Enzyme changes shape to envelope substrate(s): ES* (transition state)3. Reaction occurs producing products: Enzyme product (EP) complex4. Products lose affinity for the active site: E + P5. Enzyme is set for another substrate: E + S
  22. 22. Enzyme Specificity: Reaction Reaction specific: Enzyme catalysis is specific for one chemical reaction  Example: Sucrase is an enzyme that only catalyzes the hydrolysis of sucrose Most metabolic enzymes can catalyze a reaction in both the forward and reverse direction
  23. 23. Factors Affecting Reaction Rate A single enzyme molecule can catalyze thousands or more reactions a second Limitations to enzyme activity and thus reaction rate:  Substrate concentration  Temperature  pH  Availability of cofactors
  24. 24. Enzyme Type Simple enzyme: composed only of protein component Complex enzyme: an enzyme that requires a cofactor to function in addition to its protein component  Apoenzyme: Inactive form of the enzyme because it is missing the cofactor  Holoenzyme: Active form of the enzyme; with cofactor
  25. 25. Types of Cofactors Inorganic: metal ions  Most common: Zn, Fe, Cu Organic: usually from vitamins or their derivatives  Prosthetic group: covalently/permanently bonded to apoenzyme (e.g. heme)  Coenzyme: non-covalently/reversibly bound to apoenzyme (e.g. NADH)
  26. 26. Types of Cofactors Cofactor Inorganic Organic e.g. metal ions (vitamin derivative) Prosthetic group Coenzyme (covalently bound) (non-covalently bound) e.g. heme e.g. NADH
  27. 27. Enzyme Regulation Inhibitors:  Competitive  Noncompetitive Allosteric Regulation Cooperativity
  28. 28. Inhibitors A molecule that binds to an enzyme preventing it from catalyzing reactions. If binding involves covalent bonds, then inhibition is often irreversible. If binding is weak, inhibition may be reversible. Reversible inhibition of enzymes is a natural part of the regulation of metabolism.
  29. 29. Competitive Inhibition Inhibitor binds to the same site as the substrate Think: How do you overcome a competitive inhibitor?
  30. 30. Effect of competitive inhibitor onsaturation curve
  31. 31. Application of competitive inhibition:overcoming alcoholism
  32. 32. Noncompetitive Inhibition inhibitor binds somewhere other than the active site alters enzyme conformation rendering the active site unreceptive or less effective Think: Can you overcome noncompetitive inhibition by adding more substrate?
  33. 33. Effect of noncompetitive inhibitoron saturation curve
  34. 34. Video: Enzyme InhibitionTutorial Animation http://www.wiley.com//legacy/college/boyer/ 0470003790/animations/enzyme_inhibition/e nzyme_inhibition.htm
  35. 35. Allosteric Regulation Regulating an enzyme’s activity with a molecule that binds to the enzyme at a site removed from the active site The players:  Allosteric enzyme: has an allosteric site  Allosteric site: a specific binding site on the enzyme that is not the active site  Allosteric regulator: activator or inhibitor that binds to allosteric site
  36. 36. Allosteric Enzyme constructed of two or more polypeptide chains (subunits) each subunit has its own active site allosteric sites are often located where subunits join protein oscillates between an active and an inactive conformational shape
  37. 37. Allosteric Regulators  Allosteric regulators either inhibit or stimulate an allosteric enzyme’s activity by binding weakly to an allosteric siteAllosteric activator: stabilizesthe conformation that has afunctional active siteAllosteric inhibitor: stabilizesthe conformation that lacksan active site (inactive form)
  38. 38. Example of Allosteric RegulationFeedback inhibition metabolic pathway is turned off by its end product (acts as an inhibitor) product is abundant: pathway turned off product is rare: pathway is active
  39. 39. Tutorials
  40. 40. Cooperativity binding of a substrate to one active site stabilizes favorable conformational changes at all the other subunits can only occur in enzymes with multiple subunits amplifies the response of enzymes to substrates, priming the enzyme to accept additional substrates
  41. 41. HW Question Compare noncompetitive inhibition and allosteric inhibition. Compare allosteric activation and cooperativity. Remember: “Compare” means you’re looking at both similarities and differences. And the similarities should indicate the relationship between the 2 items and the reasons why they are being compared in the first place.