PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 4110-1MCB 450Lecture 10Principles of Enzyme CatalysisFree Energy and EquilibriaKeq and G in Living CellsActivation EnergyEnzyme-Substrate InteractionsNote: 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 precursorsMust take place at a rate that meets a cell's needsMust be specific:A particular reactant should always yield a specific productSide-reactions producing useless or toxic by-products must be minimizedEnzymes accelerate reactions and are highly specificMost reactions in biological systems don't take place in the absence of enzymes, which are catalystsEnzymes greatly enhance reaction ratesEnzymes are highly specific in: the chemical reaction they catalyzethe reactant(s) they work with (= substrates)Enzymes accelerate reactions under physiological conditions10-2 Chemical reactions in cellscarbonic acid+ carbonic anhydrase:106 molecules CO2 hydrated / sec ~107 fold rate enhancement by carbonic anhydrase10-3Carbonic anhydrase action facilitates transport of CO2 from the tissueswhere 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) of78 million years in neutral aqueous solution at room temp.10-4 Rate enhancements by enzymes*RATIO OF THE RATE OF AN ENZYME-CATALYZED REACTIONTO THE UNCATALYZED RATE = MEASURE OF CATALYTIC POWERfor thrombinfor trypsin10-5 Enzyme specificityExample: proteasesMORE SPECIFIC THAN TRYPSIN:CLEAVES ONLY ARG-GLY BONDS INPARTICULAR 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 amountsbecause 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 activity10-6 More about enzymes10-7 Classes of enzymes 1. Oxidoreductasestransfer electrons between molecules: catalyze oxidation-reduction reactions2. Transferasestransfer functional groups between molecules3. Hydrolasescleave molecules by the addition of water(Book has hydrolyase)http://www.studyblue.com/notes/note/n/lecture-3-enzymes/deck/996730e.g., Trypsin 3.4.21.4Chymotrypsin 3.4.21.1http://www.studyblue.com/notes/note/n/lecture-3-enzymes/deck/9967304. Lyasesadd atoms or functional groups to a double bond,or remove them to form double bonds10-8 Classes of enzymes 5. Isomerasesmove functional groups within a molecule6. Ligasesjoin two molecules at the expense ofATP 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 vitaminscan serve as transient carriers of electrons or specific functional groups2. 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 usuallycarry 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, 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 reactantsG determines whether the reaction will occur spontaneously2. The free energy required to initiate the conversion of reactantsinto productsThis determines the rate of the reactionFree energy change, G10-11ENZYMES AFFECT THISSome thermodynamic considerations∆G = energy available to do work in a chemical reactionThe larger the value for ∆G, the farther away the reaction is from equilibriumIn biochemistry, ΔG is the criterion for predicting equilibrium and spontaneity / favorabilityof a biochemical reaction 10-1210-13 Predicting spontaneity of a reaction from GFor reaction A + B C + D 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 or reverse directions) G ≠ 0: Reaction will spontaneously proceed to a state of lower G(i.e. towards equilibrium)….G < 0: Reaction will proceed spontaneouslyin the forward () directionG > 0: Reaction will proceed spontaneouslyin the reverse () direction∆Greaction = ∆Gproducts - ∆GreactantsProgress curve for an exergonic reaction10-14 - 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"Progress curve for endergonic reaction10-15 - When the reactants contain less free energy than the productsthe 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"- 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
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