1. 1 An Introduction to Metabolism chapter 8

2. Energy & Matter Universe is composed of 2 things …… Universe is composed of 2 things …… Energy Energy  Ability to do work o Force on an object that causes it to move Matter Matter  Anything that has mass and occupies space  Atoms/elements 2

3. 3 Metabolism transforming matter and energy Metabolism -- totality of an organism’s chemical reactions Metabolism -- totality of an organism’s chemical reactions  Arises from interactions between molecules within the cell

4. 4 Organization of the Chemistry of Life into Metabolic Pathways A metabolic pathway begins with a specific molecule and ends with a product A metabolic pathway begins with a specific molecule and ends with a product Each step is catalyzed by a specific enzyme Each step is catalyzed by a specific enzyme Enzyme 1 AB Reaction 1 Enzyme 2 C Reaction 2 Enzyme 3 D Reaction 3 Product Starting molecule

5. 5 Catabolic pathways -- release energy Catabolic pathways -- release energy  break down complex molecules into simpler compounds Anabolic pathways -- consume energy Anabolic pathways -- consume energy  build complex molecules from simpler ones Bioenergetics -- study of how organisms manage their energy resources Bioenergetics -- study of how organisms manage their energy resources Kinds of Pathways

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7. Chemical Reactions Functionality Functionality  Catabolic  Anabolic Energy Requirements Energy Requirements  Endergonic  Exergonic 7

8. 8 Chemical Reactions Reactions can be categorized as exergonic or endergonic based on energy gain or loss Reactions can be categorized as exergonic or endergonic based on energy gain or loss Chemical reactions require initial energy input (activation energy) Chemical reactions require initial energy input (activation energy)  Molecules need to be moving with sufficient collision speed  The electrons of an atom repel other atoms and inhibit bond formation

9. 9 Energy The ability to do work The ability to do work  Work -- force on an object that causes it to move  What’s moving? Two kinds of energy Two kinds of energy  Kinetic  Potential – can be positional

10. 10 The two fundamental types The two fundamental types  Kinetic -- energy of movement o Heat (thermal energy) -- random movement of atoms or molecules  Potential -- stored energy (can be because of location!) o Chemical energy -- available for release in a chemical reaction What Is Energy?

11. 11 Overview: The Energy of Life Living cell -- miniature chemical factory Living cell -- miniature chemical factory Energy transformed and stored Energy transformed and stored Energy observed in many forms Energy observed in many forms

12. 12 The Laws of Energy Transformation Thermodynamics -- study of energy transformations Thermodynamics -- study of energy transformations  Describe availability & usefulness of energy Closed system -- isolated from its surroundings Closed system -- isolated from its surroundings Open system -- energy and matter can be transferred between the system and its surroundings Open system -- energy and matter can be transferred between the system and its surroundings

13. An open hydroelectric system  G < 0  G = 0 A closed hydroelectric system  G < 0 Closed and open hydroelectric systems can serve as analogies

14. 14 Laws of Thermodynamics First -- In any process, the total energy of the universe remains constant. First -- In any process, the total energy of the universe remains constant.  Principle of conservation of energy  Energy can be transferred and transformed  Energy cannot be created or destroyed Second -- The entropy of an isolated system not in equilibrium will tend to increase over time, approaching a maximum value at equilibrium. Second -- The entropy of an isolated system not in equilibrium will tend to increase over time, approaching a maximum value at equilibrium.  During every energy transfer or transformation, energy is “ lost ” (the amount of useable energy decreases; disorder increases)

15. Thermodynamics 15

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17. Entropy Entropy – randomness Entropy – randomness  Energy conversions increase entropy in the universe Spontaneous processes increase entropy Spontaneous processes increase entropy  Explosions; car rusting Non-spontaneous process – energy input Non-spontaneous process – energy input  Rocks rolling uphill 17

18. Enthalpy Enthalpy (H) – total potential energy of system Enthalpy (H) – total potential energy of system  Total energy = Usable Energy + Unusable Energy Entropy (S) – randomness or disorder (unusable energy) Entropy (S) – randomness or disorder (unusable energy) Free Energy (G) – energy available to do work Free Energy (G) – energy available to do work  ΔG -- change in free energy  ΔG = ΔG final – ΔG initial  A negative ΔG – spontaneous Note – as entropy increases, free energy decreases Note – as entropy increases, free energy decreases 18

19. Free Energy & Stability 19

20. 20 Exergonic Reactions Exergonic reactions release energy Exergonic reactions release energy  Reactants contain more energy than products

21. 21 Exergonic Reactions Exergonic reactions release energy Exergonic reactions release energy  Reactants contain more energy than products

22. 22 Endergonic Reactions Endergonic reactions require an input of energy Endergonic reactions require an input of energy  Products contain more energy than reactants

23. 23 Endergonic Reactions Endergonic reactions require an input of energy Endergonic reactions require an input of energy  Products contain more energy than reactants

24. 24 Coupled Reactions Exergonic reactions drive endergonic reactions Exergonic reactions drive endergonic reactions  The product of an energy-yielding reaction fuels an energy-requiring reaction in a coupled reaction The parts of coupled reactions often occur at different places within the cell The parts of coupled reactions often occur at different places within the cell Energy-carrier molecules transfer the energy within cells Energy-carrier molecules transfer the energy within cells

25. 25 ATP powers cellular work by coupling exergonic reactions to endergonic reactions Cells do work: Cells do work:  Mechanical  Transport  Chemical Cells manage energy resources by energy coupling: the use of an exergonic process to drive an endergonic one Cells manage energy resources by energy coupling: the use of an exergonic process to drive an endergonic one

26. 26 The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) -- cell’s energy shuttle ATP (adenosine triphosphate) -- cell’s energy shuttle ATP provides energy for cellular functions ATP provides energy for cellular functions

27. 27 Hydrolysis of ATP High energy phosphate bonds -- broken by hydrolysis High energy phosphate bonds -- broken by hydrolysis Energy release -- chemical change to a state of lower free energy, not from the phosphate bonds themselves Energy release -- chemical change to a state of lower free energy, not from the phosphate bonds themselves

28. 28 Energy from ATP hydrolysis can be used to drive an endergonic reaction Energy from ATP hydrolysis can be used to drive an endergonic reaction  Overall, the coupled reactions are exergonic

29. NH 2 Glu P i P i P i P i NH 3 P P P ATP ADP Motor protein Mechanical work: ATP phosphorylates motor proteins Protein moved Membrane protein Solute Transport work: ATP phosphorylates transport proteins Solute transported Chemical work: ATP phosphorylates key reactants Reactants: Glutamic acid and ammonia Product (glutamine) made + + +Phosphorylation

30. 30 The Regeneration of ATP ATP -- renewable resource ATP -- renewable resource  regenerated by addition of a phosphate group to ADP The energy comes from catabolic reactions in the cell The energy comes from catabolic reactions in the cell The potential energy stored in ATP drives most cellular work The potential energy stored in ATP drives most cellular work

31. LE 8-12 P i ADP Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy- yielding processes) ATP +

32. 32 Exergonic Reactions Exergonic reactions release energy Exergonic reactions release energy  Spontaneous?

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34. 34 The Activation Energy Barrier Chemical reactions -- bond breaking and bond forming Chemical reactions -- bond breaking and bond forming The initial energy -- free energy of activation, or activation energy (E A ) The initial energy -- free energy of activation, or activation energy (E A ) E A often supplied in the form of heat from the surroundings E A often supplied in the form of heat from the surroundings

35. LE 8-14 Transition state CD A B EAEA Products CD A B  G < O Progress of the reaction Reactants C D A B Free energy

36. 36 How Enzymes Catalyze Reactions Lowering Energy of Activation (E A ) Lowering Energy of Activation (E A ) Enzymes do not affect the change in free-energy Enzymes do not affect the change in free-energy  hasten reactions that would occur eventually Biological catalysts Biological catalysts  Specific for the molecules they catalyze  Activity often enhanced or suppressed by their reactants or products

37. LE 8-15 Course of reaction without enzyme E A without enzyme  G is unaffected by enzyme Progress of the reaction Free energy E A with enzyme is lower Course of reaction with enzyme Reactants Products

38. 38 Catalysts Catalyst -- chemical agent that speeds up a reaction without being consumed by the reaction Catalyst -- chemical agent that speeds up a reaction without being consumed by the reaction Enzyme -- catalytic protein Enzyme -- catalytic protein Example: Hydrolysis of sucrose by sucrase Example: Hydrolysis of sucrose by sucrase Sucrose C 12 H 22 O 11 Glucose C 6 H 12 O 6 Fructose C 6 H 12 O 6

39. 39 Enzymes are a type of protein that acts as a catalyst, speeding up chemical reactions Enzymes are a type of protein that acts as a catalyst, speeding up chemical reactionsEnzymes Substrate (sucrose) Enzyme (sucrose) Fructose Glucose Enzymes can perform their functions repeatedly, functioning as workhorses that carry out the processes of life Enzymes can perform their functions repeatedly, functioning as workhorses that carry out the processes of life

40. LE 8-17 Enzyme-substrate complex Substrates Enzyme Products Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Active site (and R groups of its amino acids) can lower E A and speed up a reaction by acting as a template for substrate orientation, stressing the substrates and stabilizing the transition state, providing a favorable microenvironment, participating directly in the catalytic reaction. Substrates are converted into products. Products are released. Active site is available for two new substrate molecules.

41. LE 8-18 An enzyme’s activity can be affected by: An enzyme’s activity can be affected by:  General environmental factors o temperature o pH  Chemicals that specifically influence the enzyme Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant bacteria) Temperature (°C) Optimal temperature for two enzymes 020 40 6080100 Rate of reaction Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) pH Optimal pH for two enzymes 0 Rate of reaction 1 23 45 67 8 910

42. LE 8-19 Competitive -- bind to the active site of an enzyme Competitive -- bind to the active site of an enzyme Noncompetitive -- bind to another part of an enzyme Noncompetitive -- bind to another part of an enzyme  changes shape  makes active site less effective Substrate Active site Enzyme Competitive inhibitor Normal binding Competitive inhibition Noncompetitive inhibitor Noncompetitive inhibition A substrate can bind normally to the active site of an enzyme. A competitive inhibitor mimics the substrate, competing for the active site. 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.

43. 43 Regulation of enzyme activity helps control metabolism Chemical chaos -- if cell’s metabolic pathways were not tightly regulated Chemical chaos -- if cell’s metabolic pathways were not tightly regulated Cells switch genes on or off that encode specific enzymes Cells switch genes on or off that encode specific enzymes

44. 44 Allosteric Regulation of Enzymes Enzymes -- active and inactive forms Enzymes -- active and inactive forms  The binding of activator -- stabilizes the active form  The binding of an inhibitor -- stabilizes the inactive form

45. 45 LE 8-20a Allosteric enzyme with four subunits Regulatory site (one of four) Active form Activator Stabilized active form Active site (one of four) Allosteric activator stabilizes active form. Non- functional active site Inactive form Inhibitor Stabilized inactive form Allosteric inhibitor stabilizes inactive form. Oscillation Allosteric activators and inhibitors function affected by binding of a regulatory molecule at another site Allosteric regulation

46. 46 Allosteric Regulation Cooperativity -- can amplify enzyme activity Substrate Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation. Cooperativity another type of allosteric activation Stabilized active form Inactive form

47. 47 Feedback Inhibition End product of a metabolic pathway shuts down the pathway End product of a metabolic pathway shuts down the pathway Intermediate A Isoleucine used up by cell Feedback inhibition Active site of enzyme 1 can’t bind theonine pathway off Isoleucine binds to allosteric site Intermediate B Intermediate C Intermediate D End product (isoleucine)