Energy and Metabolism

1. Energy and Metabolism

2. The Energy of Life • The living cell generates thousands of different reactions • Metabolism • Is the totality of an organism’s chemical reactions • Arises from interactions between molecules • An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics

3. Course of reaction without enzyme EA without enzyme EA with enzyme is lower Reactants Free energy ∆G is unaffected by enzyme Course of reaction with enzyme Products Progress of the reaction Enzymes Lower the EA Barrier

4. Enzymes Are Biological Catalysts that… • Are proteins that carry out most catalysis in living organisms. • Are highly specific that can speed up only one or a few chemical reactions. • Have unique three-dimensional shape that enables an enzyme to stabilize a temporary association between substrates. • It is not changed or consumed in the reaction, only a small amount is needed, and can then be reused. • By controlling which enzymes are made, a cell can control which reactions take place in the cell.

5. Substate Active site Enzyme Substrate Specificity of Enzymes • Almost all enzymes are globular proteins with one or more active sites on their surface. • The substrate is the reactant an enzyme acts on • Reactants bind to the active site to form an enzyme-substrate complex. • The 3-D shape of the active site and the substrates must match, like a lock and key

6. Enzyme- substrate complex Substrate Specificity of Enzymes • Binding of the substrates causes the enzyme to adjust its shape slightly, leading to a better induced fit. • Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction • When this happens, the substrates are brought close together and existing bonds are stressed. This reduces the amount of energy needed to reach the transition state.

7. 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site can lower EA and speed up a reaction by • acting as a template for substrate orientation, • stressing the substrate bonds and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. Substrates Enzyme-substrate complex 6 Active site Is available for two new substrate Mole. Enzyme 5 Products are Released. 4 Substrates are converted into Products. Products Figure 8.17 The Catalytic Cycle Of An Enzyme

8. The substrate, sucrose, consists of glucose and fructose bonded together. 3 1 2 4 Fructose Glucose The substrate binds to the enzyme, forming an enzyme-substrate complex. Products are released, and the enzyme is free to bind other substrates. Bond H2O The binding of the substrate and enzyme places stress on the glucose-fructose bond, and the bond breaks. Active site Enzyme The Catalytic Cycle Of An Enzyme

9. Factors Affecting Enzyme Activity • Temperature - rate of an enzyme-catalyzed reaction increases with temperature, but only up to an optimum temperature. • pH - ionic interactions also hold enzymes together. • Inhibitors and Activators

10. Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria Rate of reaction 80 0 20 100 40 Temperature (Cº) (a) Optimal temperature for two enzymes Effects of Temperature and pH • Each enzyme has an optimal temperature in which it can function

11. Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Rate of reaction 5 6 7 8 9 3 4 0 2 1 (b) Optimal pH for two enzymes Figure 8.18 Effects of Temperature and pH • Each enzyme has an optimal pH in which it can function

12. Factors Affecting Enzyme Activity • Inhibitor - substance that binds to an enzyme and decreases its activity – feedback • Competitive inhibitors - compete with the substrate for the same active site • Noncompetitive inhibitors - bind to the enzyme in a location other than the active site • Allosteric sites - specific binding sites acting as on/off switches

13. A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor (b) Competitive inhibition Enzyme Inhibitors • Competitive inhibitors bind to the active site of an enzyme, competing with the substrate

14. A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition Enzyme Inhibitors • Noncompetitive inhibitors bind to another part of an enzyme, changing the function

15. Regulation Of Enzyme Activity Helps Control Metabolism • Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated • To regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymes

16. Regulation Of Enzyme Activity Helps Control Metabolism • Allosteric regulation is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site • Enzymes change shape when regulatory molecules bind to specific sites, affecting function

17. The term allostery comes from the Greek allos, "other", andstereos, "solid (object)", in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site.

18. Allosteric Activation and Inhibition • Most allosterically regulated enzymes are made from polypeptide subunits • Each enzyme has an active and an inactive form

19. Allosteric Activation The binding of an activator stabilizes the active form of the enzyme.

20. Allosteric Inhibition The binding of an inhibitor stabilizes the inactive form of the enzyme

21. Allosteric activaterstabilizes active from Allosteric enyzmewith four subunits Active site(one of four) Regulatorysite (oneof four) Activator Active form Stabilized active form Allosteric activaterstabilizes inactive form Oscillation Inhibitor Non-functionalactivesite Stabilized inactiveform Inactive form (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.

22. Binding of one substrate molecule toactive site of one subunit locks all subunits in active conformation. Substrate Inactive form Stabilized active form (b)Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate. Cooperativity • Is a form of allosteric regulation that can amplify enzyme activity

23. Factors Affecting Enzyme Activity • Activators - substances that bind to allosteric sites and keep the enzymes in their active configurations - increases enzyme activity • Cofactors - chemical components that facilitate enzyme activity • Coenzymes - organic molecules that function as cofactors

24. Regulation of Biochemical Pathways • Biochemical pathways must be coordinated and regulated to operate efficiently. • Advantageous for cell to temporarily shut down biochemical pathways when their products are not needed

26. Positive Feedback in Coagulation

27. Initial substrate(threonine) Active siteavailable Threoninein active site Enzyme 1(threoninedeaminase) Isoleucineused up bycell Intermediate A Feedbackinhibition Active site of enzyme 1 no longer binds threonine;pathway is switched off Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucine binds to allosteric site Enzyme 4 Intermediate D Enzyme 5 End product(isoleucine) In Feedback Inhibition: • The end product of a metabolic pathway shuts down the pathway • When the cell produces increasing quantities of a particular product, it automatically inhibits its ability to produce more of the substance

28. Harmful Effects of Positive Feedback • Positive feedback can be harmful. Two specific examples of these harmful outcomes would be: • Fever can cause a positive feedback within homeostasis that pushes the body temperature continually higher. If the temperature reaches 45 degrees centigrade (113 degrees Fahrenheit) cellular proteins denature bringing metabolism to a stop and death. • Chronic hypertension can favor the process of atherosclerosis which causes the openings of blood vessels to narrow. This, in turn, will intensify the hypertension and bring on more damage to the walls of blood vessels.

29. http://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htmhttp://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htm • http://www.hopkinsmedicine.org/hematology/Coagulation.swf • http://www.youtube.com/watch?v=hb92wr93JrE