From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press - 열역학 : 물질내의 물리적 화학적 변화를 동반하는 에너지변환을 연구하는 학문 - 생체에너지론 : 생물체내 에너지변환을 연구 - 생화학반응의 3 가지 중요한 인자 : 엔탈피 ( 총 열함량 ), 엔트로피 ( 무질서 ), 자유에너지 ( 화학적 일을 하는데 이용할 수 있는 에너지 ) - 자유에너지 : 화학반응의 자발성을 가름함 4.1 열역학 - 제 1 법칙 : 우주의 총 에너지는 일정, 단지 한 형태에서 다른 형태로 전환될 수 있다. - 제 2 법칙 : 우주의 무질서가 증가함, 화학반응은 무질서도가 증가하는 방향으로 -3 법칙 : 완전한 결정고체의 온도가 절대온도 영도 (0K) 에 근접할 때 무질서도는 0 에 근접하게 된다. -1,2 법칙은 생물계내의 에너지변환에 사용 - 우주 ( 시스템과 주위 ) 에서 열과 에너지변환 - 시스템 ? 열린 시스템 : 물질과 에너지는 시스템과 주위 사이에 교환됨 닫힌 시스템 : 에너지만 교환 - 글루코스분자의 에너지함량은 같다 : 일과 열로 변환

Chapter 4 Section 4.1: Section 4.1: Thermodynamics Section 4.2: Section 4.2: Free Energy Section 4.3: Section 4.3: The Role of ATP Energy Overview From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  Energy is the basic constituent of the universe  Energy is the capacity to do work  In living organisms, work is powered with the energy provided by ATP  Thermodynamics is the study of energy transformations that accompany physical and chemical changes in matter  Bioenergetics is the branch that deals with living organisms From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  Three laws of thermodynamics:  First Law of Thermodynamics—Energy cannot be created nor destroyed, but can be transformed  Second Law of Thermodynamics—Disorder always increases  Third Law of Thermodynamics—As the temperature of a perfect crystalline solid approaches absolute zero, disorder approaches zero From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  Bioenergetics is especially important in understanding biochemical reactions  These reactions are affected by three factors:  Enthalpy—total heat content  Entropy—state of disorder  Free Energy—energy available to do chemical work From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  First two laws are powerful biochemical tools  Thermodynamic transformations take place in a universe composed of a system and its surroundings  Energy exchange between a system and its surroundings can happen in two ways: heat (q) or work (w)  Work is the displacement or movement of an object by force Figure 4.1 A Thermodynamic Universe From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

(1) 제 1 법칙 -ΔE = q + w ( 시스템의 에너지변화 = 주위로부터 시스템에 의해 흡수된 에너지 + 주위에 의해 시스템에 행해진 일 ) -( 화학자 ) H= E + PV ( 엔탈피 = 압력 - 부피일 ) -ΔH = ΔE ( 일정한 압력의 생화학반응에서 ): 생물계의 총에너지의 변화가 시스템에 의해 방출 혹은 흡수된 에너지와 같음 -ΔH 0, 흡열반응 -ΔH 반응 = ΣΔH 생성물 – ΣΔH 반응물 - 문제 (2) 제 2 법칙 - 반응이 일어나는지의 예측, 자발적인지 ? - 모든 자발적인 반응과정은 우주의 총 질서를 증가시키는 방향으로 일어난다 ( 그림 4.2) - 휘발유연소시 탄소원자들이 무작위로 분산된다 ( 그림 4.3) - 엔트로피 (S): 자발적인 반응에 대해 양성

Section 4.1: Thermodynamics  First Law of Thermodynamics  Expresses the relationship between internal energy (E) in a closed system and heat (q) and work (w)  Total energy of a closed system (e.g., our universe) is constant   E = q + w  Unlike a human body, which is an open system  Enthalpy (H) is related to internal energy by the equation: H = E + PV   H is often equal to  E (  H =  E) From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  First Law of Thermodynamics Continued  If  H is negative (  H <0) the reaction gives off heat: exothermic  If is  H positive (  H >0) the reaction takes in heat from its surroundings: endothermic  In isothermic reactions (  H =0) no heat is exchanged  Reaction enthalpy can also be calculated:   H reaction =  H products   H reactants  Standard enthalpy of formation per mole (25°C, 1 atm) is symbolized by  H f ° From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  As a result of spontaneous processes, matter and energy become more disorganized  Gasoline combustion  The degree of disorder is measured by the state function entropy (S) Figure 4.3 Gasoline Combustion From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

4.2 자유에너지 - 엔트로피측정의 불가능, 자유에너지를 유도 -ΔS= ΔS 주위 + ΔS 시스템 -ΔS 주위 는 특정 화학적 또는 물리적 변화가 일어나는 동안 K 온도에 대해 교환된 열의 양 : = -ΔH/T - -T ΔS 우주 = ΔH - T ΔS 시스템 --T ΔS 우주 는 깁스자유에너지변화 또는 ΔG 라 함 -ΔG= ΔH - T ΔS - 그림 4.4: 자유에너지 변화는 ΔS 우주가 양성일 때 음성인데, 이는 자발적인 반응이 자유에너지감소 (exergonic) 반응임을 나타낸다. -ΔG=0 면 그 반응은 평형상태임 (1) 표준자유에너지 - 표준자유에너지 ΔG 0 는 용질 1.0M 농도, 1.0 기압, 25 0 C 에서 일어나는 반응 - 자유에너지변화는 반응의 평형상수와 관련 ( 정반응과 역반응의 반응속도가 동일할 때 ) - 평형상태 (ΔG=0) 에서 ΔG 0 = -RTlnKeq -Keq 를 알면 ΔG 0 계산가능 -ΔG 0 ’: 대부분 생화학반응은 pH7.0 부근에서 일어나고, 생체에너지론에서 1M 용질표준에서 일어나므로 이같이 표기 - 문제 4.3

Section 4.1: Thermodynamics  Second Law of Thermodynamics  Physical or chemical changes resulting in a release of energy are spontaneous  Nonspontaneous reactions require constant energy input  All spontaneous processes occur in the direction that increases disorder Figure 4.2 A Living Cell as a Thermodynamic System From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.1: Thermodynamics  Second Law of Thermodynamics Continued  Entropy change for the universe is positive for every spontaneous process   S univ =  S sys +  S surr  Living systems do not increase internal disorder; they increase the entropy of their surroundings  For example, food consumed by animals to provide energy and structural materials needed are converted to disordered waste products (i.e., CO 2, H 2 O and heat)  Organisms with a  S univ = 0 or equilibrium are dead From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.2: Free Energy  Free energy is the most definitive way to predict spontaneity  Gibbs free energy change or  G  Negative  G indicates spontaneous and exergonic  Positive  G indicates nonspontaneous and endergonic  When  G is zero, it indicates a process at equilibrium Figure 4.4 The Gibbs Free Energy Equation From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.2: Free Energy  Standard Free Energy Changes  Standard free energy,  G°, is defined for reactions at 25°C,1 atm, and 1.0 M concentration of solutes  Standard free energy change is related to the reactions equilibrium constant, K eq   G° = -RT ln K eq  Allows calculation of  G° if K eq is known  Because most biochemical reactions take place at or near pH 7.0 ([H + ] = 1.0  M), this exception can be made in the 1.0 M solute rule in bioenergetics  The free energy change is expressed as  G°′ From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

(2) 짝지어진반응 ( 연관반응 ) - 화학반응에서 자유에너지 값은 연속반응에서 덧셈이 가능 ( 문제 4.4-5) - 그림 4.5 은 연관반응의 예 : 부분적으로는 가능하지 않지만 (3) 소수성효과의 재검토 4.3 ATP 의 역할 -ATP 의 가수분해로 자유에너지제공 ( 그림 4.6) -ATP 의합성 : ADP 와 Pi( 오로토인산 또는 무기인산 ) 로부터 합성 ( 그림 4.7) -ATP 는 아데닌, 리보오스, 삼인산으로 구성된 뉴클레오티드임 ( 그림 4.8) 두 개의 말단 인산기 (PO 4 2- ) 는 무수인산결합 -ATP 가수분해, 인산기 전이전위 : 생체 내 전이 ( 표 4.1) - 포스포엔올피루브산과 비슷한 전이전위 ( 그림 4.9) - 무수인산결합 : 높은 에너지 - 왜 ATP 가수분해가 자유에너지감소반응인가 ?(115 페이지 ) ( 그림 4.10) ( 읽을거리 : 심해의 산화환원 - 에너지생성메카니즘, 무기반응에 의한 에너지획득 - 리토트롭 등 - 질소화박테리아, 유황박테리아 (H 2 S 의 산화 ))

 Coupled Reactions  Many reactions have a positive  G°′  Free energy values are additive in a reaction sequence  If a net  G°′ is sufficiently negative, forming the product(s) is an exergonic process Figure 4.5 A Coupled Reaction Section 4.2: Free Energy From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 Conversion of glucose-6-phosphate to fructose-1,6- bisphosphate  First step is endergonic (  G°′ = +1.7 kJ/mol) so the reaction should not proceed Figure 4.5 A Coupled Reaction Section 4.2: Free Energy From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 The second reaction is exergonic (  G°′ = kJ/mol) due to cleavage of ATP’s phosphoanhydride bond  The overall  G°′ for the coupled reactions is negative (  G°′ = kJ/mol); therefore, the reaction does proceed in the direction written at standard conditions Figure 4.5 A Coupled Reaction Section 4.2: Free Energy From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.2: Free Energy  The Hydrophobic Effect Revisited  Understanding the spontaneous aggregation of nonpolar substances is enhanced by understanding thermodynamic principles  The aggregation decreases the surface area of their contact with water, increasing its entropy  The free energy of the process is negative; therefore, it proceeds spontaneously  Spontaneous exclusion of water is important in membrane formation and protein folding From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 Adenosine triphosphate is a nucleotide that plays an extraordinarily important role in living cells  Hydrolysis of ATP  ADP + P i provides free energy Figure 4.6 Hydrolysis of ATP Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 Drives reactions of several types: 1. Biosynthesis of biomolecules 2. Active transport across membranes 3. Mechanical work such as muscle contraction Figure 4.7 The Role of ATP Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 Structure of ATP is ideally suited for its role as universal energy currency  Its two terminal phosphoryl groups are linked by phosphoanhydride bonds  Specific enzymes facilitate ATP hydrolysis Figure 4.8 Structure of ATP Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 The tendency of ATP to undergo hydrolysis is an example of its phosphoryl group transfer potential  ATP acts as energy currency, because it can carry phosphoryl groups from high-energy compounds to low-energy compounds Figure 4.9 Transfer of Phosphoryl Groups Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

 Several factors need to be considered to understand why ATP is so exergonic: 1. At physiological pH, ATP has multiple negative charges Figure 4.10 Contributing Structure of the Resonance Hybrid of Phosphate Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

2. Because of resonance stabilization, the products of ATP hydrolysis are more stable than resonance- restricted ATP  Resonance is when a molecule has two or more alternative structures that differ only in the position of their electrons Figure 4.10 Contributing Structure of the Resonance Hybrid of Phosphate Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

3. Hydrolysis products of ATP are more easily solvated 4. Increase in disorder with more molecules Section 4.3: The Role of ATP From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press