1. The Importance of Energy Changes and Electron Transfer in Metabolism Mar. 17, 2016 CHEM 281

2. Standard States for Free-Energy Changes  Standard states  for pure solids and liquids, the pure substance  for gases, the gas at a pressure of 1 atm  for solutions, a concentration of 1 mol/L  For the reaction We can rewrite the equation that relates the  G for the reaction under any conditions to the free-energy change under standard conditions (  G˚)

3. A Modified Standard State for Biochemical Applications  Standard free energy change,  G°, assumes a concentration of 1 M  if [H + ] = 1 M, then pH = 0  but the pH in most cells is near the neutral range  For biochemical reactions, we define a different standard state for the concentration of H +  standard state for [H + ] = 10 -7 M, pH = 7.0  this modified standard state is given the symbol  G°’  Summary The usual thermodynamic standard state implies that the system involved is at pH=0, which is seldom, if ever, found in living things. The modified standard state explicitly states that the system is at pH=7

4. Thermodynamics

5. The Nature of Metabolism Metabolism: the chemical reactions of biomolecules. It is the biochemical basis of life processes catabolism: the breakdown of larger molecules into smaller ones; an oxidative process that releases energy anabolism: the synthesis of larger molecules from smaller ones; a reductive process that requires energy

6. A Comparison of Catabolism and Anabolism Metabolism is the sum total of the chemical reactions of biomolecules in an organism

7. The Role of Oxidation and Reduction in Metabolism Oxidation-Reduction reactions are those in which electrons are transferred from a donor to an acceptor oxidation: the loss of electrons; the substance that loses the electrons is called a reducing agent reduction: the gain of electrons; the substance that gains the electrons is called an oxidizing agent Carbon in most reduced form- alkane Carbon in most oxidized form- CO 2 (final product of catabolism

8. Standard States for Free-Energy Changes (Cont’d)  When the reaction is at equilibrium,  G = 0 If we can determine the concentration of reactants and products at equilibrium, we can determine K eq and, from it, the change in free energy for conversion of one mole of reactant to product(s)

9. Summary  In catabolism, large molecules are broken down to smaller products, releasing energy and transferring electrons to acceptor molecules of various sorts. The overall process is one of oxidation.  In anabolism, small molecules react to give rise to larger ones; this process requires energy and involves acceptance of electrons from a variety of donors. The overall process is one of reduction

10. Coenzymes used in Biologically important Redox Reactions  Conversion of ethanol to acetaldehyde is a two-electron oxidation

11. NAD + /NADH: An Important Coenzyme  Nicotinamide adenine dinucleotide (NAD + ) is an important coenzyme  Acts as a biological oxidizing agent  The structure of NADH is comprised of a nicotinamide portion. It is involved in the reaction. It is a derivative of nicotinic acid  NAD + is a two-electron oxidizing agent, and is reduced to NADH

12. The Structures and Redox States of the Nicotinamide Coenzymes

13. FAD/FADH 2  Flavin adenine dinucleotide (FAD) is also a biological oxidizing agent  Protons, as well as, electrons are accepted by FAD

14. The Structures of Riboflavin, Flavin Mono- nucleotide (FMN), and Flavin Dinucleotide (FAD)

15. Coupling of Production and Use of Energy  The coupling of energy-producing and energy-requiring reactions is a central theme in the metabolism of all organisms  Energy cannot be used directly, must by shuttled into easily accessible forms of chemical energy  “High Energy” bonds- bonds that require or release convenient amounts of energy, depending on the direction of the reaction  ATP is essential high energy bond-containing compound  Phosphorylation of ADP to ATP requires energy  Hydrolysis of ATP to ADP releases energy

16. The Phosphoric Anhydride Bonds in ATP are “High Energy” Bonds

17. ATP  4 (-) charges on ATP and 3 on ADP, therefore ATP is less stable.  Why is ATP less stable, charge-wise, than ADP?  Energy must be expended to put on additional negative charge on ADP  Also, entropy loss when ADP is phosphorylated because there is a potential loss of resonance hybridization of inorganic phosphate (P i ) upon phosphorylation of ADP to ATP

18. Loss of a Resonance-Stabilized Phosphate Ion in Production of ATP

19. ATP Hydrolysis Decreases in Electrostatic Repulsion  Marked decrease in electrostatic repulsion of  -phosphate of ADP upon hydrolysis of ATP to ADP

20. Organophosphates Important in Producing Energy

21. Role of ATP as Energy Currency

22. Summary  Hydrolysis of ATP to ADP releases energy  In the coupling of biochemical reactions, the energy released by one reaction, such as ATP hydrolysis, provides energy for another

23. Coenzyme A in Activation of Metabolic Pathways A step frequently encountered in metabolism is activation activation: the formation of a more reactive substance A metabolite is bonded to some other molecule and the free-energy change for breaking the new bond is negative. Causes next reaction to be exergonic

24. Two Ways of Looking at Coenzyme A Coenzyme A (CoA-SH) contains units of 2- mercaptoethylamine, pantothenic acid, and 3’,5’-ADP

25. The Hydrolysis of Acetyl-CoA  The metabolically active form of a carboxylic acid is the corresponding acyl-CoA thioester, in which the thioester linkage is a high-energy bond

26. The Role of Electron Transfer and ATP Production in metabolism

27. Summary  Metabolic pathways proceed in many stages, allowing for efficient use of energy  Many coenzymes, particularly coenzyme A(CoA) play a crucial role in metabolism