10 1 MCB 450 Lecture 10 Principles of Enzyme Catalysis Free Energy and Equilibria Keq and G in Living Cells Activation Energy Enzyme Substrate Interactions Note Reading for Lecture 11 pre lecture 11 Qs is Chapter 7 Sections 1 and 2 10 2 Chemical reactions in cells 1000s of different reactions go on in cells nutrient molecules are degraded chemical energy is conserved and transformed macromolecules are made from simple precursors Must take place at a rate that meets a cell s needs Must be specific A particular reactant should always yield a specific product Side reactions producing useless or toxic by products must be minimized Enzymes accelerate reactions and are highly specific Most reactions in biological systems don t take place in the absence of enzymes which are catalysts Enzymes greatly enhance reaction rates Enzymes are highly specific in substrates the chemical reaction they catalyze the reactant s they work with 10 3 107 fold rate enhancement by carbonic anhydrase carbonic anhydrase 106 molecules CO2 hydrated sec carbonic anhydrase 0 13 molecules CO2 hydrated sec carbonic acid Carbonic anhydrase action facilitates transport of CO2 from the tissues where it is produced to the lungs where it is exhaled 10 4 Rate enhancements by enzymes RATIO OF THE RATE OF AN ENZYME CATALYZED REACTION TO THE UNCATALYZED RATE MEASURE OF CATALYTIC POWER Orotic acid is decarboxylated with a half time t of 78 million years in neutral aqueous solution at room temp 1 2 10 5 Enzyme specificity Example proteases for trypsin for thrombin MORE SPECIFIC THAN TRYPSIN CLEAVES ONLY ARG GLY BONDS IN PARTICULAR PEPTIDE SEQUENCES 10 6 More about enzymes Most are proteins except small group of catalytic RNAs Catalytic activity depends on integrity of enzyme s native conformation Usually present in very small amounts because they are not consumed in reactions Activity of many enzymes is regulated Many enzymes named by adding suffix ase to the name of their substrate or a word describing their activity Some enzymes require no chemical groups for activity other than their own Some enzymes require additional cofactors for activity 10 7 Classes of enzymes 1 Oxidoreductases transfer electrons between molecules catalyze oxidation reduction reactions 2 Transferases transfer functional groups between molecules 3 Hydrolases cleave molecules by the addition of water Book has hydrolyase http www studyblue com notes note n lecture 3 enzymes deck 996730 e g Trypsin 3 4 21 4 Chymotrypsin 3 4 21 1 10 8 Classes of enzymes 4 Lyases add atoms or functional groups to a double bond or remove them to form double bonds 5 Isomerases move functional groups within a molecule 6 Ligases join two molecules at the expense of ATP hydrolysis http www studyblue com notes note n lecture 3 enzymes deck 996730 10 9 Enzyme cofactors Catalytic activity of many enzymes depends on presence of small molecules called cofactors Enzyme minus its cofactor apoenzyme Complete catalytically active enzyme plus its cofactor holoenzyme Two subdivisions of cofactors 1 Coenzymes small organic molecules derived from vitamins can serve as transient carriers of electrons or specific functional groups 2 Metals A coenzyme that is very tightly bound to an enzyme a prosthetic group The same coenzyme can be used by a variety of enzymes Different enzymes that use the same cofactor usually carry out similar chemical transformations 10 10 Enzyme cofactors 10 11 Some thermodynamic considerations Free energy change G When a reacting system is not at equilibrium the tendency to move towards equilibrium represents a driving force the magnitude of which can be expressed as the free energy change of the reaction G To understand how enzymes operate we need to consider two thermodynamic properties of the reaction 1 G difference between the free energy content of the products and the free energy content of the reactants G determines whether the reaction will occur spontaneously reactants 2 The free energy required to initiate the conversion of into products This determines the rate of the reaction ENZYMES AFFECT THIS 10 12 In biochemistry G is the criterion for predicting equilibrium and spontaneity favorability of a biochemical reaction G energy available to do work in a chemical reaction The larger the value for G the farther away the reaction is from equilibrium 10 13 Predicting spontaneity of a reaction from G For reaction A B C D Greaction Gproducts Greactants G 0 Reaction is at equilibrium and there is no net change in the concentrations of reactants and products no net flow in the forward reverse directions G 0 Reaction will spontaneously proceed to a state of lower G i e towards equilibrium G 0 Reaction will proceed spontaneously in the forward direction G 0 Reaction will proceed spontaneously in the reverse direction or 10 14 Progress curve for an exergonic reaction When the products contain less free energy than the reactants the reaction will proceed spontaneously and have a negative G Spontaneously means that the reaction will take place without energy input reaction actually releases energy and is called exergonic 10 15 Progress curve for endergonic reaction When the reactants contain less free energy than the products the reaction will not proceed spontaneously and will have a positive G Input of free energy is needed to drive the reaction which is called endergonic 10 16 G provides information about the spontaneity of a reaction but not its rate When a reacting system is at equilibrium there is no net change in the concentrations of reactants and products and G 0 G of a reaction depends only on the free energy of the products free energy of the reactants final state initial state G of a reaction is independent of the path molecular mechanism of the transformation G provides no information about the rate of a reaction A ve G says a reaction can occur spontaneously but does not say whether the reaction will proceed at a perceptible rate The rate of a reaction depends on the free energy of activation G 10 17 More thermodynamic considerations Equilibrium constant Keq For reaction A B C D Keq C D A B The composition of a reacting system mix of chemical reactants products tends to continue to change until equilibrium is reached At the equilibrium concentration of reactants and products rates of the forward and reverse reactions are equal and no further net change occurs in the system The concentrations of reactants and products at equilibrium define Keq The standard
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