Understanding Metabolism: Energy and Processes in Living Cells

1. Chapter 08 An Introduction to Metabolism

2. Overview: The Energy of Life • The living cell is a miniature chemical factory where thousands of reactions occur • The cell extracts energy and applies energy to perform work • Some organisms even convert energy to light, as in bioluminescence

3. Metabolic pathways in a cell

4. Figure 8.1 What causes the bioluminescence in these organisms Bioluminescence: 특정 유기산에 저장된 에너지를 빛으로 전환하는 과정

5. Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics • Metabolism (물질대사) is the totality of an organism’s chemical reactions • Metabolism is an emergent property of life that arises from interactions between molecules within the cell

6. Enzyme 1 Enzyme 2 Enzyme 3 A D C B Reaction 1 Reaction 2 Reaction 3 Startingmolecule Product Organization of the Chemistry of Life into Metabolic Pathways • A metabolic pathway (대사경로) has many steps • That begin with a specific molecule and end with a product • That are each catalyzed by a specific enzyme

7. Metabolism의 분류 • Catabolic pathways (이화작용 경로) • Break down complex molecules into simpler compounds • Release energy (예: 세포호흡) • Anabolic pathways (동화작용 경로) • Build complicated molecules from simpler ones • Consume energy (예: 단백질합성) 생명체의 대사경로는 에너지를 기반으로 발생하므로 세포의 활동을 이해하기 위해서는 에너지에 대한 기초지식이필요

8. 에너지 형태에는 어떤 것이 있나? • Energy • Is the capacity to cause change • Exists in various forms, of which some can perform work

9. Kinetic energy (운동에너지) • Is the energy associated with motion • Heat or thermal energy (열 또는 열에너지) - Is kinetic energyassociated with the random movement of atoms or molecules • Potential energy (위치 에너지) : 물질의 위치나 구조 덕분에 갖게 되는 저장된 형태의 에너지 • Is stored in the location of matter (활동적이지 않으며 비축된 에너지 형태) • Includes chemical energy stored in molecular structure (예: ATP) • Chemical energy (화학에너지)는 화학반응에서 방출되는 위치에너지

10. A diver has more potentialenergy on the platformthan in the water. Diving convertspotential energy tokinetic energy. • Energy can be converted : From one form to another (에너지 형태는 전환가능함) 운동에너지와 위치에너지 사이의 전환 (Transformations between potential and kinetic energy) Climbing up converts the kineticenergy of muscle movementto potential energy. A diver has less potentialenergy in the waterthan on the platform. Figure 8.2

11. The Laws of Energy Transformation • Thermodynamics (열역학) • Is the study of energy transformations (물질을 포함하는 우주 속에서의 에너지 변환에 관한 학문) System (계) 물질과 에너지의 양방향 이동이 가능: 생물과 같이 열린계 (open system)의 경우 Surroundings (주변부) : system을 뺀 우주의 나머지 부분

12. The First Law of Thermodynamics (에너지 보존의 법칙) • According to the first law of thermodynamics, the energy of the universe is constant • - energy can be transferred and transformed, but it cannot be created or destroyed 에너지전환의 예 Chemicalenergy 곰이 획득한 연어로부터 전환된 화학에너지는 운동에너지 등으로 변환될 수 있음. 그러면 과연 이런 운동에너지의 운명은? (a) First law of thermodynamics Fig. 8.3a

13. The Second Law of Thermodynamics • During every energy transfer or transformation, some energy is unusable, and is often lost as heat • According to the second law of thermodynamics • Every energy transfer or transformation increases the entropy (disorder) of the universe 모든 형태의 에너지 이동이나 전환은 우주의 무질서도 (엔트로피)를 증가시킨다

14. Figure 8.3b Heat (b) Second law of thermodynamics – 곰이 획득한 에너지 중 변환된 형태의 화학에너지는 움직임으로 변환됨. – 대부분은 열 또는 대사의 부산물인 이산화탄소나 물 등의 분자로 바뀌어 주변부로 전달되어 우주의 무질서도를 증가시키게 됨

15. Biological Order and Disorder • Cells create ordered structures from less ordered materials • Organisms also replace ordered forms of matter and energy with less ordered forms • Energy flows into an ecosystem in the form of light and exits in the form of heat • The evolution of more complex organisms does not violate the second law of thermodynamics • Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases (생명체내의 질서 유지에는 에너지가 필요함)

16. Figure 8.4 질서는 생명체의 특성이다 성게 (sea urchin) 선인장

17. Concept 8.2: The free-energy change of a reaction tells us whether the reaction occurs spontaneously • Biologists want to know which reactions occur spontaneously and which require input of energy • To do so, they need to determine energy changes that occur in chemical reactions

18. 자유에너지 변화란무엇인가? • A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell • Free-Energy Change, G (for J. Williard Gibbs, Prof. at Yale Univ. in 1878) 화학반응의 자유에너지 변화를 알게 되면 화학반응이 자발적으로 일어나는 지 아니면 에너지 투입이 필요한 것인지를 이해하게 된다

19. The change in free energy, ∆Gduring a biological process • Is related directly to the enthalpy change(∆H) and the change in entropy(∆S) • ∆G = ∆H – T∆S [T: K(켈빈)단위의 절대온도] •  ∆G은 화학반응이 외부 에너지 공급없이 자발적으로 일어날 수 있는 지 없는 지를 결정하는 데 이용될 수 있음 • ∆G < 0 : 자발적인 반응 (자유에너지 감소; 엔탈피 감소, 엔트로피 증가와 관련됨)

20. Free Energy, Stability, and Equilibrium 생명체는 자유에너지 소모를 통해 안정한 계가 되려고 한다: ∆G = Gfinal - Gfirst • During a spontaneous change • Free energy decreases and the stability of a system increases • 모든 계는 안정도가 높아지는 방향 또는 자유에너지는 감소하는 방향으로 가는 경향 있음 • 안정성이 최고조인 상태를 “평형 (equilibrium)”이라 함

21. 자유에너지, 안정화, 일능력, 자발적인 변화의 관계? • 안정성이 최고조인 상태를 “평형 (equilibrium)”이라 함 포도당의 분해과정 염료 분자 다이빙 • More free energy (higher G)• Less stable• Greater work capacity In a spontaneous change• The free energy of the system decreases (G 0)• The system becomes more stable• The released free energy can be harnessed to do work • Less free energy (lower G)• More stable• Less work capacity (a) Gravitational motion (b) Diffusion (c) Chemical reaction 중력운동 화학반응 확산 계의 안정성이 최고치에 도달한 것이 평형이다 Figure 8.5

22. Reactants Amount of energy released (∆G <0) Free energy Energy Products Progress of the reaction Figure 8.6 (a) Exergonic reaction: energy released 자유에너지 개념은 생명체의 물질대사에도 적용될 수 있다! Exergonic (발열)and Endergonic(흡열)Reactions in Metabolism • An exergonic reaction • Proceeds with a net release of free energy and is spontaneous (자유에너지 방출/자발적)

23. Products Amount of energy released (∆G>0) Free energy Energy Reactants Progress of the reaction Figure 8.6 (b) Endergonic reaction: energy required • An endergonic reaction • Is one that absorbs free energy from its surroundings and is nonspontaneous (주변부로부터 자유에너지 흡수/비자발적)

24. Equilibrium and Metabolism (평형과 물질대사) 평형에 도달하는 것은 생명체에게는 죽음이다 그렇다면 생명체는 어떻게 평형에 도달하지 않고 살아 갈 수 있나?

25. ∆G < 0 ∆G = 0 (a) A isolated hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium. Figure 8.7 A • Reactions in a isolated system • Eventually reach equilibrium • 닫힌 계에서는 평형상태로 가게 되며, 일을 할 수 없게 됨. 페쇄된 수력발전

26. ∆G < 0 (b) An open hydroelectric system. Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equlibrium. Figure 8.7 • Cells in our body (=열린계) • Experience a constant flow of materials in and out, preventing metabolic pathways from reaching equilibrium (물질의 계속적인 출입현상이 일어나므로 대사과정이 평형에 도달하는 것을 방지함) 열린 수력발전

27. ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucoce is brocken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction reaches equilibrium. Figure 8.7 영생의 길은 가능한 가? • An analogy for cellular respiration (세포호흡은 다단계로 구성된 열린 수력발전 계와 유사함) 산소+포도당 이산화탄소+물 세포에서는 연료인 포도당과 산소를 공급받을 수 있고, 이산화탄소 및 물과 같은 노폐물 제거가 지속적으로 가능하다면 평형에 도달하지 않고 생명체로서 영원히 일을 수행할 수 있음

28. Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions • A cell does three main kinds of work • Mechanical (기계적인) : 편모, 섬모의 운동성, 근수축 등 • Transport (수송 작업): 막단백질에 의한 능동수송 등 • Chemical (화학적 작업): 광합성에 의한 중합체 합성 등

29. 어떻게 이런 일들을 할 수 있을까? • Energy coupling (에너지 연계) • Is a key feature in the way cells manage their energy resources to do this work • 세포가 여러 작업을 수행하는 데 있어 에너지 자원을 관리하는 방법 중 하나 • 발열반응을 이용하여 흡열반응을 수행하는 데 필요함 • ATP는 세포내의 대부분의 에너지 연계에 필요한 직접적인 에너지원

30. The Structure and Hydrolysis of ATP • ATP (adenosine triphosphate) is the cell’s energy shuttle • ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups Adenine Phosphate groups Ribose (a) The structure of ATP Figure 8.8

31. Figure 8.8b • Energy is released from ATP (ATP로부터 에너지 방출) • When the terminal phosphate bond is broken Adenosine triphosphate (ATP) Energy Inorganicphosphate Adenosine diphosphate (ADP) (b) The hydrolysis of ATP

32. How ATP Performs Work? • The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP • In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction • Overall, the coupled reactions are exergonic • ATP에 의한 흡열반응의 유도는 인산화를 통해 인산기를 다른 분자(흡열반응의 반응물)에 전이시킴으로써 가능하며 • 결국 연계반응은 발열반응이 된다

33. Glutamic acidconversionto glutamine (a) Conversionreactioncoupledwith ATPhydrolysis (b) (c) Free-energychange forcoupledreaction How ATP drives chemical work: Energy coupling using ATP hydrolysis NH3 NH2 GGlu = +3.4 kcal/mol Glu Glu Glutamine Ammonia Glutamicacid NH3 P 2 1 NH2 ADP ADP P i ATP Glu Glu Glu Phosphorylatedintermediate Glutamicacid Glutamine GGlu = +3.4 kcal/mol NH2 NH3 P i ADP ATP Glu Glu GGlu = +3.4 kcal/mol GATP = 7.3 kcal/mol + GATP = 7.3 kcal/mol Net G = 3.9 kcal/mol Figure 8.9

34. Figure 8.10 Q: How ATP drives transport and mechanical work? Transport protein Solute ATP ADP P i P P i Solute transported (a) Transport work: ATP phosphorylates transport proteins. Cytoskeletal track Vesicle ATP ADP P i ATP Motor protein Protein andvesicle moved (b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed.

35. The Regeneration of ATP (ATP는 전지(배터리)와 같다) • ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP) • The energy to phosphorylate ADP comes from catabolic reactions in the cell • The ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways

36. ATP hydrolysis to ADP + Piyields energy ATP synthesis from ADP + Pi requires energy ATP Energy from catabolism (exergonic, energy yielding processes) Energy for cellular work (endergonic, energy- consuming processes) ADP + P i Figure 8.11 ATP Cycle • Catabolic pathways • Drive the regeneration of ATP from ADP and phosphate + H2O

37. Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers (에너지장벽) • 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

38. How does the enzyme do this? Sucrase Glucose(C6H12O6) Fructose(C6H12O6) Sucrose(C12H22O11)

39. 활성화에너지 장벽? • The activation energy, EA • Is the initial amount of energy needed to start a chemical reaction (화학반응의 개시에 필요한 에너지로 반응물을 전이상태로 끌어 올리는 데 사용됨) • Is often supplied in the form of heat from the surroundings in a system (종종 주변부로부터 열에너지 형태로 공급됨) • 반응속도를 결정하는 장벽 역할 • 열은 단백질변성, 세포죽음을 초래할 수 있고, 모든 반응에 작용하므로 특이성이 없음. • 따라서 생물계에서는 EA장벽을 낮추는 대안으로 효소와 같은 촉매를 사용함

40. Figure 8.12 발열반응의 에너지 흐름도 A B D C Transition state 화학결합이절단된 후 새로운 결합이 생성되며 에너지가 주변으로 방출된다 A B EA D C Free energy Reactants A B 반응물은주변으로부터 충분한 에너지를 획득하여 불안정한 전이상태에 도달하게 되며 화학결합이 끊어지게 된다 G O C D Products Progress of the reaction

41. How Enzymes Lower the EA Barrier? • Enzymes catalyze reactions by lowering the EA barrier • Enzymes do not affect the change in free energy (∆G); instead, they hasten (=hurry) reactions that would occur eventually

42. An enzyme catalyzes reactions By lowering the EA barrier (높지 않은 보통 수준의 온도에서도 반응분자가 쉽게 전이상태에 도달할 수 있게 충분한 에너지를 흡수할 수 있게 EA장벽을 낮춤. 이때 free-energy change에는 영향을 미치지 않음) Course ofreactionwithoutenzyme EAwithoutenzyme EA withenzymeis lower Reactants Course ofreactionwith enzyme G is unaffectedby enzyme Free energy Products Progress of the reaction Figure 8.13

43. 효소의 작용기작은? Substrate Specificity of Enzymes (효소의 기질특이성) • 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(활성부위는 기질의 화학그룹에 맞게 적합한 형태로 전환될 수 있음)

44. Induced fit between an enzyme and its substrate Substrate Active site Enzyme Enzyme-substratecomplex (a) (b) Hexokinase and glucose Figure 8.14

45. 효소의 활성부위는 어떻게 활성화 에너지 장벽을 낮추나? Catalysis in the Enzyme’s Active Site • In an enzymatic reaction, the substrate binds to the active site of the enzyme • The active site can lower an EA barrier by • Orienting substrates correctly(기질의 정확한 배열 유도) • Straining substrate bonds(기질결합을 압박하여 전이상태 안정화) • Providing a favorable microenvironment(우호적인 미세환경 제공) • Covalently bonding to the substrate(촉매반응에 직접 참여하여 기질과 공유결합 형성)

46. 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. 3Active site (and R groups of its amino acids) can lower EA 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 Enzyme-substrate complex 6 Active site Is available for two new substrate Mole. Enzyme 5 Products are Released. 4 Substrates are Converted into Products. Figure 8.15 Products • The catalytic cycle of an enzyme

47. Effects of Local Conditions on Enzyme Activity • The activity of an enzyme • Is affected by general environmental factors • Effects of Temperature and pH • Cofactors: nonprotein enzyme helpers Zn, Fe, Cu (아연, 철, 구리와 같은 무기이온) orcoenzymesuch as vitamins (organic) • Enzyme Inhibitors

48. Enzyme Inhibitors • 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

49. 효소 활성의 억제는 어떻게 일어나나? (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Substrate Activesite Competitiveinhibitor Enzyme Noncompetitiveinhibitor Figure 8.17

50. Concept 8.5: Regulation of enzyme activity helps control metabolism • Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated • A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes