Essential Elements of Biochemistry BCHM 3050 Dr Srikripa Chandrasekaran Lecture 2 6 15 Notes Enzymes Part 3 Mechanisms of Enzyme Regulation Activation Inhibition Modification I General Mechanisms of Enzyme Regulation A Genetic Regulation The amount of enzyme that is used is regulated B Substrate vs Product Availability Can produce more product by introducing more enzyme If you do not want an enzyme to go crazy overactive then you can introduce an inhibitor which can stop or slow down the enzyme C Mechanism of Inhibition An enzyme inhibitor substrate complex is not very efficient Usually inhibitors usually bind to the free enzyme or to the enzyme substrate complex Inhibitors come and go they can bind to the enzyme or the enzyme substrate complex but then they can let go so that some product is eventually produced II Three Main Types of Inhibitors A Competitive Inhibitors Competes with the enzyme to bind to the active site of the enzyme in order to completely block the enzyme from binding to the substrate Km increases Vmax remains the same Binding to the active site If malonate binds to the enzyme the enzyme changes shape slightly in order to correctly fit the malonate This blocks the enzyme from binding to the substrate Half the Vmax Km To achieve the same affinity you need a very high amount of substrate concentration With the inhibitor the Km is higher which means you need much more substrate in order to achieve the same velocity and affinity Km is increased with inhibitor essentially this is a waste of substrate As you increase the inhibitor the Km increases A competitive inhibitor increases the Km but does not alter the Vmax B Non Competitive Inihibitor Km remains the same Vmax decreases Binding to the enzyme or the enzyme substrate complex but not to the active site Cannot reverse this inhibitor A non competitive inhibitor is more permanent C Un Competitive Inhibitor Km decreases Vmax decreases Binding to the enzyme substrate complex but not active site cannot bind to a free enzyme Binds only to the enzyme substrate complex cannot bind to a free enzyme Un competitive inhibitor lowers the Km and the Vmax the tighter the substrate binds to the enzyme the more the Km and the Vmax both decrease Designer HIV Protease Inhibitors A Can combine competitive inhibitors and non competitive inhibitors in order to have both inhibitor types work together and make it more difficult for resistance to be developed Covalent Modification of Enzymes A Covalent modification When you stick a functional group on the enzyme so that it cannot function any more this inactivates the enzyme very few enzymes get inhibited by being covalently modified B When you modify an amino acid enzyme you can inactive it C Sometimes an enzyme needs a phosphate groups to function so if you remove the phosphate group then you inactivate that enzyme Allosteric Regulation of Enzymes A Sometimes inhibitors can bind to a site other than the active site of the enzyme and these types of inhibitors are called allosteric B Substrate Velocity Curves for an Allosteric Enzyme 1 With an inhibitor the curve will shift to the right 2 With an activator the curve will shift to the left Effects of Temperature A Some enzymes functional at extreme temperatures B Many enzymes become denatured at extremely high temperatures this is why fevers are very dangerous III IV V VI
View Full Document
Unlocking...