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Cell and Molecular Biology Fifth Edition CHAPTER 3 Part 1 Bioenergetics, Enzymes, and Metabolism Copyright © 2008 by John Wiley & Sons, Inc. Gerald Karp

3.1 Bioenergetics: Definition: Study of the various types of energy transformations that occurs in living organisms. Thermodynamics: Study of the changes in energy that accompany events in the universe involving energy flow and predicating the reaction direction

1.The laws of thermodynamics and the concept of entropy a. Energy b. The first law of thermodynamics c. The second law of thermodynamics d. Free energy

The first law of thermodynamics: The law of conservation of energy, energy can neither be created nor destroyed but can be converted.

b. Energy change during transformation ∆E = Q – W (first law of thermodynamics) E: internal energy of a system (or a cell) Q: heat energy W: working energy ∆E: (energy change during transformation) +, or –, or 0 related to the surroundings It gives no information as to the likelihood that a given event will occur

C. The second law of thermodynamics 1. Spontaneous: proceed “down hill” from higher energy to lower energy state. 2. They are thermodynamically favorable and occur without the input of external energy. 3. Loss of energy in a spontaneous process results the disorders or randomness, (energy unavailable for additional work) 4. Entropy: T∆S energy/degree or cal/deg 5. Every event is accompanied by an increase in the entropy of the universe. Lowering the entropy in the system while raise that of environment

In living system aa → protein, the entropy decreased, but the entropy of the environment increased Other macromolecules Need energy Glycogen stored in liver are converted to heat, CO 2 and H 2 O → produced free radicals) and shorter life spin

d. Free energy: energy available to do work 1878 J. Willard Gibbs ∆ H (total energy) = ∆G + T ∆S If ∆G is -, exergonic reaction, proceed toward state of lower free energy If ∆G is +, endogonic reaction, proceed toward state of higher free energy If ∆H is +, system gains heat, if ∆H is -, system lost heat. If ∆S is +, system became more disorder. if ∆S is -, system became more order ∆G (free energy) = ∆ H - T ∆S

∆G = ∆ H - T ∆S

1. Free energy changes in chemical reactions All reactions proceed toward equilibrium A+B ↔ C+D Keq = (C)(D)/(A)(B) = K 1 /K 2 ( K 1,K 2 : rate constant ) ex: (C)(D)/(A)(B) = (0.5)(0.5)/(0.5)(0.5) = 1 If Keq > 1, reaction will proceed to right direction If Keq < 1, reaction will proceed to left direction

∆G o ， (Standard free energy in biochemistry aspect): at standard conditions: 25 o C(298 o K), 1 atm, 1M conc. pH7.0 ∆G o ‘ = RTlogKeq‘ If Keq‘>1, ∆G o ‘ is negative, spontaneous reaction If Keq‘<1, ∆G o ‘ is positive, reaction can’t occur spontaneously

Concentrations of reactants and products that are present at the time ∆G = ∆G o ， RTlog[C][D]/[A][B]

2. Free energy changes in metabolic reactions ATP + H 2 O ↔ ADP + Pi ∆G o‘ = -7.3 Kcal/mol In cell, (ATP) = 10 mM, (ADP) = 1 mM, (Pi) = 10 mM So, ∆G = ∆G o‘ + 2.3RTlog (ADP)(Pi)/(ATP) = ·10 -2 /10 -2 = (10 -3 ) = Kcal/mole

Equilibrium versus steady-state metabolism Cellular metabolism is essentially nonequilibrium metabolism As reactions tend toward equilibrium, the free energy available to do work decreases toward minimum Some reactions are near equilibrium, but some other reactions are far from the equilibrium. These are the reactions that keep the pathway going in a single direction.

3.2 Enzymes as a Biological Catalysts The properties of enzymes: require only a small amount, they are not altered irreversibly, they have no effect on the thermodynamics Overcoming the activation energy barrier The active site and molecular specificity Enzyme kinetics

Three mechanisms by which enzymes accelerate reactions 1. maintaining precise substrate orientation (lower entropy of substrates) 2. changing substrate reactivity by altering its electrostatic structure 3. exerting physical stress on bonds in the substrate to be broken (induced fit)

Time-resolved x-ray crystallographs (study conformational changes and catalytic intermediates) Ultra-high density x-ray cut the x-ray exposure period to picosec (enzymatic reaction). Cooling protein (enzyme) to K to increase the life time by 10 billion and can study the intermediates Synchronize the reaction by inert ATP molecules by linking nitrophenyl group 3-D image at 0.8 A

3.3 Metabolism Oxidation and Reduction: A matter of electrons The capture and utilization of energy Metabolic regulation

Altering enzyme activity by covalent modification, ex: protein kinase Altering enzyme activity by allosteric modulation : feedback inhibition (ATP) Separate catabolic and anabolic pathways