BCHM 3050 1st Edition Lecture 12 Outline of Last Lecture I How does liquidy syrup inside candies form II Substrate Concentration has the Greatest Effect III Initial Velocity is Fastest IV Importance of Vmax and Km V Significance of Km VI Experimental Determination of Vmax and Km VII The Michaelis Menton Equation VIII Lineweaver Burk Plots Outline of Current Lecture I General Mechanisms of Enzyme Regulation II Three Main Types of Inhibitors a Competitive b Non competitive c Uncompetitive III Designer Drugs for AIDS IV Covalent Modification of Enzymes V Allosteric Regulation of Enzymes VI Other Factors that Regulate Enzyme Activity Current Lecture These 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 I General Mechanisms of Enzyme Regulation a Genetic Regulation i Majority of enzymes are proteins so they are regulated ii Enzyme activity is controlled by genetics DNA iii DNA decides how much enzyme will be available when it will react b Substrate vs Product Availability i Can tip the balance towards the product by altering the amount of enzyme present or the concentration of substrate ii Add inhibitors to decrease enzyme activity or recognize the presence of an inhibitor and take it away to increase rate of reaction c Mechanisms of Inhibition i Suicide Inhibitors are those that not only bind to the active site of an enzyme but more importantly react with the active site to become permanently bound to the enzyme ii Modern rational drug design uses this strategy in making new drugs iii Penicillin is a good example of a suicide inhibitor i e it inhibits transpeptidase from building bacterial cell walls iv Inhibitor can directly take over the enzyme form an Enzyme InhibitorySubstrate complex gets very low products v Inhibitors come and go but this is reversible so eventually you get a product II Three Main Types of Inhibitors a Competitive i Competitive Inhibitor looks very similar to the substrate so it competes with the substrate to try to bind to the activation site and block out substrate ii If Malonate binds to the active site the enzyme changes in shape inactivating enzyme iii Competitive inhibitory causes more substrate needing to be added iv Put in more substrate to get the same product of the reaction v Km increases in the presence of an inhibitor which means you need much more of the substrate to achieve the same level of affinity vi Vmax is not alerted by competitive inhibitor b Non competitive i Non Competitive Inhibition doesn t bind to active site doesn t affect Km and reduces Vmax ii This inhibitor is more permanent than competitive inhibitors not reversible c Uncompetitive i Un Competitive Inhibitor binds only to the enzyme substrate complex lowers both Km and Vmax ii Km decreases but velocity also decreases III Designer Drugs for AIDS a The HIV virus is a complex enveloped or coated virus that causes AIDS b Targeting the Protease enzyme c Original genetic material is RNA rather than DNA in the HIV virus uses reverse transcriptase single stranded RNA is easier to manipulate d Send inhibitors to enzyme protease to try to target the virus e Aspartate protease simply means that aspartic acid two residiues in the active site are involved in proteolysis f Inactivate the protease not allow the virus to continue g Protease was a drug target h Protease breaks the bond between Tyr and Pro IV i Can now design an inhibitor against the protease to inhibit the enzyme function j Inhibitor is blocking the active site of the protease Covalent Modification of Enzymes a Covalent Modification the reversible attachment of a functional group onto a protein or enzyme via a covalent bond i Very few amino acids are in inhibited this way ii Enzymes of glycogen metabolism storage or breakdown are regulated by phosphorylation dephosphorylation iii Removing disulfide bond between cysteines inactivates enzymes V Allosteric Regulation of Enzymes a Allosteric includes non competitive and uncompetitive inhibitors and activators can be allosteric b Allosteric means other site c Activator curve becomes more hyperbolic and shift to the left d Inhibitor curve shifts to the right VI Other Factors that Regulate Enzyme Activity a Availability of co factors i Metal ions ii Co enzymes iii pH iv Temperature
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