Mechanism of enzyme action

Mechanism of enzyme action

• 1.
  Mechanism of Enzyme Action
• 2.
  Enzymes • Biocatalyst • Proteinin nature • Active Sites • Efficiency • Specificity • Holoenzymes • Regulation • Location 3D Model of an Enzyme
• 3.
  Mechanism of EnzymeAction • An enzyme allows a reaction to proceed rapidly under conditions prevailing in the cell by providing an alternate reaction pathway with a lower free energy of activation. • The enzyme does not change the free energies of the reactants or products and, therefore, does not change the equilibrium of the reaction. • It does accelerate the rate with which equilibrium is reached. • The rate enhancement (ratio of the rates of the catalyzed and uncatalyzed reactions) is given by eΔΔG ‡ cat/RT
• 4.
  Catalytic Mechanisms 1. Acid–basecatalysis 2. Covalent catalysis 3. Metal ion catalysis 4. Proximity and orientation effects 5. Preferential binding of the transition state complex
• 5.
  Acid–Base Catalysis
• 6.
  Bovine Pancreatic RNaseA • Secreted by pancreas into small intestine • Hydrolyzes RNA to component nucleotides X-Ray structure of bovine pancreatic RNase A
• 9.
  Covalent Catalysis
• 10.
  Covalent Catalysis Examples
• 11.
  Metal Ion Catalysis CarbonicAnhydrase Mechanism
• 12.
  Catalysis Through Proximityand Orientation Effects Intermolecular Reaction Intramolecular Reaction is 24 times faster
• 13.
  Orientation of SN2reaction Any deviation from this optimal geometry would increase the free energy of the transition state and reduces the rate of the reaction.
• 14.
  Catalysis Through PreferentialBinding of the Transition State Complex • An enzyme may bind the transition state of the reaction it catalyzes with greater affinity than its substrates or products! • The more tightly an enzyme binds its reaction’s transition state relative to the substrate, the greater is the rate of the catalyzed reaction relative to that of the uncatalyzed reaction. • Where transition state stabilization makes only a minor contribution to rate enhancement the enzyme promotes the reaction by instead stabilizing the so-called near attack conformation, a step along the reaction coordinate in which the reactants are properly oriented and in van der Waals contact but have not yet reached the transition state.
• 15.
  Proof! Proline Analogs Proline racemaseis inhibited by the planar analogs of proline, pyrrole- 2-carboxylate and Δ-1-pyrroline-2-carboxylate, both of which bind to the enzyme with 160-fold greater affinity than does proline. These compounds are therefore thought to be analogs of the transition state in the proline racemase reaction.
• 16.
  References • Voet, D.;Voet, J.; Pratt, C.W.; Fundamentals of Biochemistry Life at the Molecular Level, 5th Edition, Wiley • Berg, J.M.; Tymoczko, J.L.; Stryer, L; Biochemistry, 7th Edition, W.H. Freeman and Company New York • Harvey, R.A.; Ferrier, D.R.; Lippincott’s Illustrated Reviews: Biochemistry, 5th Edition, Wolters Kluwer • Nelson, D.L.; Cox, M.; Lehninger Principles of Biochemistry, 7th Edition, W.H. Freeman
• 17.
  Thank You.