How Enzymes Lower the E A. Barrier. Substrate Specificity of Enzymes. Enzymes catalyze reac.ons by lowering the E A barrier

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1 How Enzymes Lower the E A Barrier Enzymes catalyze reac.ons by lowering the E A barrier do not affect the change in free energy ( G) Instead hasten reac.ons that would occur eventually Fig Free energy Course of reaction without Reactants Course of reaction with E A without E A with is lower G is unaffected by Progress of the reaction Products Substrate Substrate Specificity of Enzymes The reactant that an acts on The binds to its substrate, forming an substrate complex Ac>ve site region on the where the substrate binds Induced fit Forma.on of substrate complex triggers conforma.onal change in brings chemical groups of the ac.ve site into posi.ons that enhance their ability to catalyze the reac.on By contor.ng and stressing bonds in substrate

2 Fig Substrate Enzyme Enzyme-substrate complex (a) (b) Catalysis in the Enzyme s Ac>ve Site s Ac>ve Site In an enzyma.c reac.on, the substrate binds to the ac.ve site of the The ac.ve site can lower an E A barrier by Orien.ng substrates correctly Straining substrate bonds Providing a favorable microenvironment Covalently bonding to the substrate Fig Substrates enter active site; changes shape such that its active site enfolds the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates Enzyme-substrate complex 3 can lower E A and speed up a reaction. 6 Active site is available for two new substrate molecules. Enzyme 5 Products are released. 4 Substrates are converted to products. Products

3 Effects of Temperature and ph Each has An op.mal temperature for func.on Taq polymerase at 95 C An op.mal ph for func.on Pepsinogen/pepsin at ph 2 Not necessarily the same for all s Fig Rate of reaction Optimal temperature for typical human Optimal temperature for of thermophilic (heat-tolerant) bacteria Temperature (ºC) (a) Optimal temperature for two s Rate of reaction Optimal ph for pepsin (stomach ) Optimal ph for trypsin (intestinal ) ph (b) Optimal ph for two s Cofactors Cofactors nonprotein helpers may be inorganic (such as a metal in ionic form) or organic Co organic cofactor include vitamins Vitamin C ascorbic acid

4 Enzyme Inhibitors Compe>>ve inhibitors bind to the ac.ve site of an, compe.ng with the substrate Block ac.ve site Noncompe>>ve inhibitors bind to another part of an cause to change shape altering ac.ve site Examples of inhibitors include toxins, poisons, pes.cides, and an.bio.cs Fig Substrate Competitive inhibitor Enzyme (a) Normal binding (b) Competitive inhibition Noncompetitive inhibitor (c) Noncompetitive inhibition Allosteric Regula>on of Enzymes Allosteric regula>on may either inhibit or s.mulate an s ac.vity occurs when a regulatory molecule binds to a protein at one site and affects the protein s func.on at another site Can be a form of non compe..ve inhibi.on

5 Allosteric Ac>va>on and Inhibi>on Most allosterically regulated s are made from individual polypep.de subunits Each with its own ac.ve site Each has ac.ve and inac.ve forms binding of an ac.vator stabilizes the ac.ve form of the binding of an inhibitor stabilizes the inac.ve form of the Allosteric with four subunits (one of four) Regulatory site (one of four) Activator Active form Stabilized active form Oscillation Nonfunctional active site Inhibitor Inactive form (a) Allosteric activators and inhibitors Stabilized inactive form Coopera>vity Allosteric Regula>on a form of allosteric regula.on that can amplify ac.vity binding by a substrate to one ac.ve site stabilizes favorable conforma.onal changes at all other subunits Substrate Inactive form Stabilized active form (b) Cooperativity: another type of allosteric activation

6 Feedback Inhibi>on Feedback inhibi>on the end product of a metabolic pathway shuts down the pathway Feedback inhibi.on prevents a cell from was.ng chemical resources by synthesizing more product than is needed Fig Initial substrate (threonine) available Threonine in active site Isoleucine used up by cell Feedback inhibition Isoleucine binds to allosteric site Enzyme 1 (threonine deaminase) Intermediate A Enzyme 2 of 1 no longer binds Intermediate B threonine; pathway is Enzyme 3 switched off. Intermediate C Enzyme 4 Intermediate D Enzyme 5 End product (isoleucine) You should now be able to: 1. Dis.nguish between the following pairs of terms: catabolic and anabolic pathways; kine.c and poten.al energy; open and closed systems; exergonic and endergonic reac.ons 2. In your own words, explain the second law of thermodynamics and explain why it is not violated by living organisms 3. Explain in general terms how cells obtain the energy to do cellular work 4. Explain how ATP performs cellular work 5. Explain why an investment of ac.va.on energy is necessary to ini.ate a spontaneous reac.on 6. Describe the mechanisms by which s lower ac.va.on energy 7. Describe how allosteric regulators may inhibit or s.mulate the ac.vity of an