Forms of InhibitionSequential Mechanisms (Single Displacement)Cleland NomenclatureHow to distinguish sequential mechanisms: product inhibition studiesCHEM 451 1st Edition Lecture 9Outline of Last Lecture I. One-intermediate model with reversible stepsa. Haldane RelationshipII. Two-intermediate modela. The “Black Box” AnalogyIII. The Hairpin Ribozymea. Measuring docking rate constants by FRETOutline of Current Lecture I. Forms of Inhibitiona. Lineweaver-Burk PlotsII. Cleland NomenclatureIII. Sequential MechanismsIV. Ping Pong MechanismsCurrent LectureForms of InhibitionCompetitive Uncompetitive Non-competitiveDefinition Inhibitor resembles substrate and binds directly to binding siteInhibitor binds to enzyme-substrate complex.Binds enzyme AS WELL AS enzyme-substrate complexv0wherewhereLineweaver-Burk equationThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Slopeα KMVmaxKMVmaxα KMVmaxY-intercept1Vmaxα 'Vmaxα 'VmaxWhat stays constanty-intercept Slope NoneWhat varieswith [I]Slope increases as [I] increasesy-intercept increases as [I] increasesSlope increases as [I] increasesy-intercept increases as [I] increasesConverges at:y-intercept (does not converge) To the left of y-interceptSequential Mechanisms (Single Displacement)Sequential Mechanisms – all substrates must combine with enzyme before any product can be released.Examples: trypsin binds polypeptide and water; alcohol dehydrogenase and NAD+; coenzyme is the leading reactant. Cleland NomenclatureSubstrates: ABCD in order that they add to enzymeProducts: PQRS in order that they leave enzymeStable enzyme forms: EFG; by itself cannot convert to another stable enzyme.Ordered Bi Bi: have a compulsory order of substrate addition to enzyme. A and B are said to be the leading and following substrates, respectively. Random Bi Bi: no preference for the order of substrate additionHow to distinguish sequential mechanisms: product inhibition studiesLineweaver-Burk plots are the same for random and ordered Bi Bi. Plot the Lineweaver-Burk plots, treating B and A as inhibitors on one another. Any mixed inhibition means that the sequential mechanism is ordered. The slope of each is independent of the concentration of the
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