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Transcript
Enzymes and the Arrhenius Equation Enzymes Catalysts for Biochemical Reactions Enzymes bring reactants together in the proper orientation for reaction to occur. Enzymes speed up the reaction by stabilizing the transition state. Reaction proceeds via a different mechanism in the presence of the enzyme. k=Ae-Ea/RT Enzymes lower the activation energy by allowing the reaction to proceed via a different mechanism. Enzymes increase the fraction of productive collisions by binding the reacants in the proper orientation for reaction to occur. A = pZ Enzymes How Do Enzymes Work? Reaction Mechanisms By Stabilizing the Transition State The enzyme surrounds the forming transition state with favorable interactions. Stabilization of this transition state by binding to the enzyme results in a lower activation energy, and thus a faster rate of reaction for the enzyme-catalyzed reaction. Uncatalyzed Reaction S P Energy Energy ES ES Catalyzed Reaction E + S ES ES P + E S P S P Reaction Progress Key: S = substrate E = enzyme ES = enzyme-substrate complex P = product Reaction Progress Enzyme-catalyzed reaction Uncatalyzed reaction Substrate Binding Enzyme Activity The Active Site Enzymes bind the substrate (reactants) in the active site. This is a cleft that is lined with an array of polar, non-polar, and charged amino acids arranged in such a way as to interact favorably, and selectively, with the substrate. The Native Structure Acetylcholinesterase HIV Protease Enzymes fold into a specific shape called the native structure. If the enzyme is unfolded from this structure (denatured), it no longer functions as a catalyst. The native structure is held together largely by a combination of non-covalent interactions (H-bonding, charge-charge, dispersion, etc.). If the pH or temperature conditions change from the optimal ones, these interactions are disturbed and the enzyme will denature and no longer act as a catalyst. 1 Case Study Acetylcholine Acetylcholinesterase A Neurotransmitter •Essential for nerve transmission at neuromuscular junctions (nerve-muscle connections) •Removes excess acetylcholine (neurotransmitter) from synapse allowing neuron to reload and fire next nerve impulse. •Target of nerve agents (Sarin, Tabun, Soman, etc) :O: CH3 H3C + N .. CH2 CH2 O .. CH3 C CH3 Ester Group Ammonium Group Acetylcholine is a neurotransmitter; a chemical messenger that propagates the nerve impulse across a synapse (gap between neurons). Nerve Transmission Nerve Transmission Receptors Resting State Acetylcholinesterase (AChE) clears the excess ACh out of the synapse by hydolytic cleavage. When the synaptic ACh concentration is reduced, acetylcholine diffuses away from the receptors (Le Chatelier's principle). Acetylcholine (ACh) diffuses across the synapse. When ACh binds to receptors on the other side of the synapse, it triggers changes in ion concentration that result in an electrical impulse. This signal is passed on to the next nerve and the process repeats itself down the line. = Acetylcholine (ACh) Acetylcholinesterase plays a major role in the nerve transmission process. The excess ACh present in the synapse must be removed so that the nerve cell is ready for the next nerve impulse. = Acetylcholinesterase (AChE) Reaction Catalyzed by Acetylcholinesterase Acetylcholinesterase Reverse of Condensation Reaction Catalytic Triad CH 3 H3C N + CH 3 Histidine 440 O CH 2 CH 2 O C CH 3 + H 2O Acetylcholine N + CH 3 Serine 200 O CH 3 H3C CH2 CH 2 O H + H O C Inhibitor CH 3 Glutamate 199 These three amino acids, the catalytic triad, are located at the active site and play a crucial role in catalysis. 2 Nerve Agents Nerve Agents Nerve agents work by reacting with the OH group of the active-site serine that is required for catalytic activity. This disables (inhibits) the enzyme. Sarin O F P CH3 F P CH3 CH3CH2 O P CH3 S HC CH3 H3C CH CH3 H3C C CH3 CH3 CH2 H3C CH N CH CH3 CH3 Sarin O CH2 HO ..: O O O Active Site ser VX Soman O Inhibition of Acetylcholinesterase F P CH3 O O ser CH2 O P CH3 + HF O CH CH3 CH CH3 CH3 CH3 Inactivated Enzyme CH3 Exercises 1. Draw the Lewis structure of the dipeptide Val-Ser. (Hint: The structures of these amino acids appear on the “Examples of Amino Acids” slide in this presentation.) 2. The amino acid valine has a hydrocarbon sidechain. In the native (folded) structure of a water-soluble protein, would you expect to find the majority of the valines on the exterior of the protein or in the interior. Explain your answer. 3. Which terms of the Arrhenius Equation are favorably affected by the action of enzymes? 4. A chemist measures the rate of an enzyme-catalyzed reaction as a function of temperature and obtains a relationship such as that shown in the plot below. Provide an explanation. Is this the relationship between rate and temperature that is found for reactions that do not involve enzymes? Rate Temperature 3