10-1 MCB 450 Lecture 10 Principles of Enzyme Catalysis Free Energy and Equilibria Keq and ΔG in Living Cells Activation Energy Enzyme-Substrate Interactions Note: Reading for Lecture 11 (& pre-lecture 11 Qs) is Chapter 7 Sections 1 and 2.1000s 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: the chemical reaction they catalyze the reactant(s) they work with (= substrates) Enzymes accelerate reactions under physiological conditions 10-2 Chemical reactions in cellscarbonic acid + carbonic anhydrase: 106 molecules CO2 hydrated / sec ~107 fold rate enhancement by carbonic anhydrase 10-3 Carbonic anhydrase action facilitates transport of CO2 from the tissues where it is produced to the lungs where it is exhaled - carbonic anhydrase: 0.13 molecules CO2 hydrated / sec*Orotic acid is decarboxylated with a half-time (t1/2) of 78 million years in neutral aqueous solution at room temp. 10-4 Rate enhancements by enzymes * RATIO OF THE RATE OF AN ENZYME-CATALYZED REACTION TO THE UNCATALYZED RATE = MEASURE OF CATALYTIC POWERfor$thrombin$for$trypsin$10-5 Enzyme specificity Example: proteases MORE SPECIFIC THAN TRYPSIN: CLEAVES ONLY ARG-GLY BONDS IN PARTICULAR PEPTIDE SEQUENCES- 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 αα - Some enzymes require additional cofactors for activity 10-6 More about enzymes10-7 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!http://www.studyblue.com/notes/note/n/lecture-3-enzymes/deck/996730 4. Lyases add atoms or functional groups to a double bond, or remove them to form double bonds 10-8 Classes of enzymes 5. Isomerases move functional groups within a molecule 6. Ligases join two molecules at the expense of ATP hydrolysis10-9 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 transformations10-10 Enzyme cofactors- 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, ΔG. - To understand how enzymes operate, we need to consider two thermodynamic properties of the reaction: 1. ΔG = difference between the free energy content of the products and the free energy content of the reactants ΔG determines whether the reaction will occur spontaneously 2. The free energy required to initiate the conversion of reactants into products This determines the rate of the reaction Free energy change, ΔG 10-11 ENZYMES AFFECT THIS Some thermodynamic considerations∆G = energy available to do work in a chemical reaction The larger the value for ∆G, the farther away the reaction is from equilibrium In biochemistry, ΔG is the criterion for predicting equilibrium and spontaneity / favorability of a biochemical reaction 10-1210-13 Predicting spontaneity of a reaction from ΔG For reaction A + B C + D ΔG = 0: Reaction is at equilibrium and there is no net change in the concentrations of reactants and products (no net flow in the forward or reverse directions) ΔG ≠ 0: Reaction will spontaneously proceed to a state of lower G (i.e. towards equilibrium)…. ΔG < 0: Reaction will proceed spontaneously in the forward (→) direction ΔG > 0: Reaction will proceed spontaneously in the reverse (←) direction ∆Greaction = ∆Gproducts - ∆GreactantsProgress curve for an exergonic reaction 10-14 - When the products contain less free energy than the reactants, the reaction will proceed spontaneously and have a negative ΔG - "Spontaneously" means that the reaction will take place without energy input (reaction actually releases energy), and is called "exergonic"Progress curve for endergonic reaction 10-15 - When the reactants contain less free energy than the products the reaction will not proceed spontaneously, and will have a positive ΔG - Input of free energy is needed to drive the reaction, which is called "endergonic"- When a reacting system is at equilibrium, there is no net change in the concentrations of reactants and products, and ΔG = 0 - ΔG of a reaction depends only on the [free energy of the products] – [free energy of the reactants] (final state) (initial state) - ΔG of a reaction is independent of the path (molecular mechanism) of the transformation - ΔG provides no information about the rate of a reaction. A –ve ΔG 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 ΔG ΔG provides information about the spontaneity of a
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