1. Chapter 8~ An Introduction to Metabolism

2. Metabolism/Bioenergetics Metabolism: The totality of an organism’s chemical processes; managing the material and energy resources of the cell Enzyme 1Enzyme 2Enzyme 3 A B C D Reaction 1Reaction 2Reaction 3 Starting molecule Product Metabolic Pathway begins with a specific molecule then it is altered by enzymes resulting in a different product

3. Metabolism/Bioenergetics Catabolic pathways: degradative process such as cellular respiration; releases energy by breaking down molecules Anabolic pathways: building process such as protein synthesis; photosynthesis; consumes energy to build complex molecules –Energy released from catabolic pathways can be stored and used to drive anabolic pathways Bioenergetics: study of how organisms manage their energy resources

4. Thermodynamics Energy (E)~ capacity to do work –Kinetic energy~ energy of motion (photons of light, heat/thermal) – Potential energy~ stored energy (chemical) Thermodynamics~ study of E transformations Forms of Energy

5. Energy can be TRANSFORMED! Energy can be transformed from one form to another Entropy is the quantity used as a measure of disorder or randomness Energy Transformation

6. Flow of energy through life Life is built on chemical reactions –transforming energy from one form to another organic molecules  ATP & organic molecules sun solar energy  ATP & organic molecules

7. Laws of Energy Transformation 1st Law of Thermodynamics: conservation of energy; E transferred/transformed, not created/destroyed 2nd Law of Thermodynamics: transformations increase entropy (disorder, randomness, spontaneity)

8. Living Systems are “Open” Systems Matter and energy move in to living systems from the environment. Living systems transform matter and energy and return it to the environment

9. Multi-Step Metabolism To increase control, living systems produce free energy in multiple-step pathways, mediated by enzyme catalysts.

10. Spontaneous Reaction For a process to occur on its own, without outside help, it must increase entropy of the universe

11. What drives reactions? If some reactions are “downhill”, why don’t they just happen spontaneously? –because covalent bonds are stable bonds Stable polymers don’t spontaneously digest into their monomers

12. Getting the reaction started… Breaking down large molecules requires an initial input of energy –activation energy –large biomolecules are stable –must absorb energy to break bonds energy cellulose CO 2 + H 2 O + heat Can cells use heat to break the bonds?

13. Free energy-8.2 Free energy: portion of system’s E that can perform work (at a constant T and P) tells us whether the reaction occurs spontaneously or not ∆G = ∆H –T∆S G= available energy H= enthalpy (total energy) T= temperature in K (*C+273) S= entropy (disorder)

14. Free Energy a measure of the stability of a system –high in free energy= unstable and will move toward a more stable state with less free energy compressed spring to be spontaneous the system must either give up energy (decrease H), give up order (increase S), or both ∆G must be NEGATIVE

15. ∆G = ∆H –T∆S When pushed, ball goes down slide Total enthalpy /energy (H) has decreased H to h When barrier is removed, particles spread out Entropy/disorder (S) has increased s to S REMEMBER: to be spontaneous the system must either give up energy (decrease H), give up order (increase S), or both ∆G must be NEGATIVE

16. ∆G = ∆H –T∆S (x = y - AB) What happens when you decrease y? What happens when you increase A or B? Using this to predict spontaneity: –∆G < 0 (negative= always spontaneous) –∆G> 0 (positive= never spontaneous) –∆G= 0 (system is in equilibrium) 2 nd Law of Thermodynamics: for a process to occur spontaneously, it must increase the entropy of the universe

17. (a) An isolated hydroelectric system (b) An open hydro- electric system (c) A multistep open hydroelectric system  G  0  G  0 Equilibrium vs. Disequilibrium “system”= matter under study “surroundings” = everything else in the universe –“closed system” vs. “open system” Metabolic Equilibrium

18. Why do we need to know about Free Energy? Free energy describes if a reaction is spontaneous (∆G is negative) help to perform work Living organisms must perform work to stay alive, grow and reproduce. All living organisms must possess the ability to obtain energy and to be able to transform that energy into a form that can be used by its cells.

19. Metabolic Reactions Can form bonds between molecules –dehydration synthesis –synthesis –anabolic reactions –ENDERGONIC Can break bonds between molecules –hydrolysis –digestion –catabolic reactions –EXERGONIC breaking down molecules= less organization= lower energy state building molecules= more organization= higher energy state

20. ∆G = ∆H –T∆S Exergonic reaction: net release of free E to surroundings ∆G < 0 Cell Respiration Endergonic reaction: absorbs free E from surroundings ∆G > 0 Photosynthesis SPONTANEOUS NOT SPONTANEOUS

21. Exergonic Reaction The greater the decrease in free energy (∆G ), the greater the amount of work can be done –Cell Respiration C 6 H 12 O 6 + 6 O 2  6 CO 2 + 6 H 2 O ∆G= -686 kcal/mol Endergonic Reaction The magnitude of ∆G is very high to drive the reaction - Photosynthesis 6 CO 2 + 6 H 2 O  C 6 H 12 O 6 + 6 O 2 ∆G= + 686 kcal/mol

22. 2005-2006 Energy needs of life Organisms are endergonic systems –What do we need energy for?  synthesis (biomolecules)  reproduction  active transport  movement  temperature regulation

23. ATPATP 8.3 ATP A cell does 3 main kinds of work –Mechanical –Transport –Chemical Energy Coupling- how cells manage the energy resources to do this work; mediated by ATP the use of exergonic process drives an endergonic process

24. ATP: Adenosine triphosphate ATP hydrolysis: release of free E by the breaking of the weak phosphate bonds between phosphate groups via hydrolysis –ATP  ADP + P –∆G= -7.3 kcal/mol (release of energy when phosphate is broken) highly negative tail

25. How does ATP perform work? ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant The recipient molecule is now called a phosphorylated intermediate weak bonds

26. Figure 8.11 Energy from catabolism (exergonic, energy-releasing processes) Energy for cellular work (endergonic, energy-consuming processes) ATP ADPP i H2OH2O Revolving door through which energy passes during its transfer from catabolic to anabolic

27. 8.4 Enzymes A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction An enzyme is a catalytic protein –Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme- catalyzed reaction

28. How Enzymes Work Enzyme Function Free E of activation / activation energy: (E A ): the E required to break bonds Enzymes catalyze reactions by lowering the E A barrier Enzymes do not affect the change in free energy (∆G); instead, they speed up reactions that would occur eventually

29. Activation Energy Low E A so the thermal energy provided by room temperature is enough for many reactions to reach their transition state High E A the transition state is rarely reached, so the reaction rarely proceeds- these processes need to be heated to proceed Why don't energy-rich molecules, like sucrose, spontaneously degrade into CO 2 and Water? b/c sucrose is very stable! stable molecules have high E A

30. Substrate Specificity of Enzymes The reactant that an enzyme acts on is called the enzyme’s substrate –The enzyme binds to its substrate, forming an enzyme-substrate complex The active site is the region on the enzyme where the substrate binds Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction

31. Catalytic Center In an enzymatic reaction, the substrate binds to the active site of the enzyme –Weak bonds (ionic/hydrogen) catalyze the conversion of a substrate to product which then leaves the active site The active site can lower an E A barrier by –Orienting substrates correctly –Straining substrate bonds –Providing a favorable microenvironment –Covalently bonding to the substrate

32. Substrates Substrates enter active site. Enzyme-substrate complex Enzyme Products Substrates are held in active site by weak interactions. Active site can lower E A and speed up a reaction. Active site is available for two new substrate molecules. Products are released. Substrates are converted to products. 1 2 3 4 5 6

33. Effects of Local Conditions on Enzyme Activity An enzyme’s activity can be affected by –General environmental factors, such as temperature and pH –Chemicals that specifically influence the enzyme

34. Figure 8.16 Optimal temperature for typical human enzyme (37°C) Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria (77°C) Temperature (°C) (a) Optimal temperature for two enzymes Rate of reaction 120 100 80 60 40200 0 12 3 4 5 6 78910 pH (b) Optimal pH for two enzymes Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme)

35. Cofactors Cofactors are non-protein enzyme helpersenzyme –bind permanently or reversible to the enzyme Cofactors may be inorganic (such as a metal in ionic form) or organic –An organic cofactor is called a coenzyme –Coenzymes include vitamins

36. Enzyme Inhibitors- Regulation Enzyme Inhibitors- Regulation Competitive inhibitors bind to the active site of an enzyme, competing with the substrate Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective Examples of inhibitors include toxins, poisons, pesticides, and antibiotics

37. (a) Normal binding(b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Enzyme Competitive inhibitor Noncompetitive inhibitor

38. Allosteric Activation and Inhibition Allosteric Regulation - A protein’s function at one site is affected by the binding of a regulatory molecule to a separate siteRegulation –Most allosterically regulated enzymes are made from polypeptide subunits Each enzyme has active and inactive forms; constantly changing shapes –The binding of an activator stabilizes the active form of the enzyme –The binding of an inhibitor stabilizes the inactive form of the enzyme

40. Cooperativity is a form of allosteric regulation that can amplify enzyme activity One substrate molecule primes an enzyme to act on additional substrate molecules more readily –The binding by a substrate to one active site affects catalysis in a different active site

41. Figure 8.19 Regulatory site (one of four) (a) Allosteric activators and inhibitors Allosteric enzyme with four subunits Active site (one of four) Active form Activator Stabilized active form Oscillation Non- functional active site Inactive form Inhibitor Stabilized inactive form Inactive form Substrate Stabilized active form (b) Cooperativity: another type of allosteric activation Reactants and Products of ATP hydrolysis play a major role in balancing the flow of traffic between anabolic and catabolic pathways

42. Feedback Inhibition Feedback Inhibition In feedback inhibition, the end product of a metabolic pathway shuts down the pathway –metabolic control Feedback inhibition by the use of allosteric molecules prevent a cell from wasting chemical resources by synthesizing more product than is needed

43. Figure 8.21 Active site available Isoleucine used up by cell Feedback inhibition Active site of enzyme 1 is no longer able to catalyze the conversion of threonine to intermediate A; pathway is switched off. Isoleucine binds to allosteric site. Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Intermediate A Intermediate B Intermediate C Intermediate D Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 End product (isoleucine)