Chapter 8~ An Introduction to Metabolism

1. Chapter 8~ An Introduction to Metabolism

2. Enzyme 1 Enzyme 2 Enzyme 3 A D C B Reaction 1 Reaction 2 Reaction 3 Startingmolecule Product Metabolism/Bioenergetics • Metabolism: The totality of an organism’s chemical processes; managing the material and energy resources of the cell 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 organic moleculesATP & organic molecules 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 polymersdon’t spontaneouslydigest into theirmonomers

12. energy 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 Can cells use heat to break the bonds? cellulose CO2 + H2O + heat

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 REMEMBER: to be spontaneous the system must either give up energy (decrease H), give up order (increase S), or both ∆G must be NEGATIVE • 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

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) 2nd Law of Thermodynamics: for a process to occur spontaneously, it must increase the entropy of the universe

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

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 building molecules= more organization=higher energy state breaking down molecules= less organization=lower energy state

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

21. Endergonic Reaction • The magnitude of ∆G is very high to drive the reaction • - Photosynthesis • 6 CO2 + 6 H2O  C6H12O6 + 6 O2 • ∆G= + 686 kcal/mol • Exergonic Reaction • The greater the decrease in free energy (∆G ), the greater the amount of work can be done • Cell Respiration C6H12O6 + 6 O2 6 CO2 + 6 H2O ∆G= -686 kcal/mol

22. Energy needs of life • synthesis (biomolecules) • reproduction • active transport • movement • temperature regulation • Organisms are endergonicsystems • What do we need energy for?

23. ATP 8.3 • 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 highly negative tail • 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)

25. How does ATP perform work? weak bonds • 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

26. Figure 8.11 ATP H2O Energy for cellularwork (endergonic,energy-consumingprocesses) Energy fromcatabolism (exergonic,energy-releasingprocesses) ADP P i 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: (EA): the E required to break bonds • Enzymes catalyze reactions by lowering the EA barrier • Enzymes do not affect the change in free energy (∆G); instead, they speed up reactions that would occur eventually

29. Activation Energy • Low EA so the thermal energy provided by room temperature is enough for many reactions to reach their transition state • High EA 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 CO2 and Water? b/c sucrose is very stable! stable molecules have high EA

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 EA barrier by • Orienting substrates correctly • Straining substrate bonds • Providing a favorable microenvironment • Covalently bonding to the substrate

32. Substrates enter active site. 1 2 Substrates are heldin active site by weakinteractions. Substrates Enzyme-substratecomplex Active site canlower EA and speedup a reaction. 3 6 Activesite isavailablefor two newsubstratemolecules. Enzyme Products arereleased. 5 Substrates areconverted toproducts. 4 Products

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 forenzyme of thermophilic(heat-tolerant)bacteria (77°C) Optimal temperature fortypical human enzyme (37°C) Rate of reaction 120 60 0 20 40 100 80 Temperature (°C) (a) Optimal temperature for two enzymes Optimal pH for pepsin(stomachenzyme) Optimal pH for trypsin(intestinalenzyme) Rate of reaction 0 3 5 7 8 9 10 1 2 4 6 pH (b) Optimal pH for two enzymes

35. Cofactors • Cofactors are non-protein enzyme helpers • 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 • 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 Activesite Competitiveinhibitor Enzyme Noncompetitiveinhibitor

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 site • 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 (b) Cooperativity: another type of allosteric activation (a) Allosteric activators and inhibitors Active site(one of four) Allosteric enzymewith four subunits Substrate Regulatorysite (oneof four) Activator Stabilized activeform Inactive form Stabilized active form Active form Reactants and Products of ATP hydrolysis play a major role in balancing the flow of traffic between anabolic and catabolic pathways Oscillation Inhibitor Non-functionalactive site Inactive form Stabilized inactiveform

42. 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 Initial substrate(threonine) Active siteavailable Threoninein active site Enzyme 1(threoninedeaminase) Isoleucineused up bycell Intermediate A Active site ofenzyme 1 isno longer ableto catalyze theconversionof threonine tointermediate A;pathway isswitched off. Feedbackinhibition Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucinebinds toallostericsite. Enzyme 4 Intermediate D Enzyme 5 End product(isoleucine)