Bioenergetics & Metabolism I

1. Bioenergetics & Metabolism I Objectives 1. Describe how DG can be used to predict whether a reaction can occur spontaneously 2. Derive the relationship between DG0’ and the equilibrium constant (K’eq)of a reaction 3. Explain why enzymes do not alter the equilibrium of chemical reactions but change only their rates 4. Define metabolism. Lecture 13, Michael Schweizer

2. Some 500 metabolic reactions of a typical cell are shown schematically with the reactions of glycolysis and the citric acid cycle in black

4. Approaches to Metabolism • PATHWAYS • ENERGETICS (THERMODYNAMICS) • REGULATION • CELLULAR FUNCTION / LOCALIZATION • ENZYME MECHANISM • MECHANISM

5. Introduction to Metabolism • Understanding metabolic pathways • for each step: • reaction mechanism including enzyme participation • thermodynamics --- “will it go”? • contribution to whole pathway

6. All energy forms are, in principle, interconvertible

7. THERMODYNAMICS IN BIOCHEMISTRY • SYSTEM: defined region •  SURROUNDINGS: the rest of the universe • FIRST LAW OF THERMODYNAMICS The total energy of a system and its surroundings is a constant

8. THERMODYNAMICS EA energy in a system at the start of a process EB energy in a system at the end of a process Q Heat absorbed or lost by the system from its surroundings W Work done by the system Note: path-independent DE = 0, positive or negative

10. A simple thermodynamic analysis of a living cell

11. Second Law of Thermodynamics Entropy (S): the degree of randomness or disorder in a system A process can occur spontaneously only if the sum of the entropies of the system and its surroundings increases

12. Entropy • Does it predict spontaneous reactions? _________________ •  Problems • difficult to measure • must determine Ssystem and Ssurroundings

14. Gibbs Free Energy • G Gibbs Free Energy • H Change in enthalpy (heat content) • S Change in entropy • T Absolute temperature

15. Gibbs Free Energy G < 0 A reaction can occur spontaneously G = 0 A system is at equilibrium: no net change occurs G > 0 A reaction cannot occur spontaneously. An input of free energy is required to drive the reaction.

16. Gibbs Free Energy • G is path-independent • G provides no information about rates of (enzyme-assisted) reactions

17. Enzymes cannot change the equilibrium point for reactions

18. DG and Equilibrium For the reaction A + BC + D

19. DG and Equilibrium Go standard free energy change at pH 0 (a H+ conc. of 1.0 M) T = 2980 K is equal to 250C   concentration of all reactants is 1.0 M R = 1.98 kcal mol-1 deg-1

20. DG and Equilibrium • This equation relates the nature of the reactants and their concentrations. • Gº' is the standard free energy change for biochemical reactions • pH = 7 (H+ = 10-7 M) and activity of water (55.6 M) • Concentration of all reactants = 1.0 M ’

21. Equilibrium Constants ,  Keq equilibrium constant , G = Go’ + R T lnKeq At equilibrium G = 0, then , , Go’ = -R T lnKeq

22. Equilibrium Constants ,  Keq equilibrium constant G = Go’ + R T lnKeq , , Keq Go’ (kcal/mole) 99/1 -2.8 1/99 +2.8 105/1 -7.1 1/105 +7.1

23. Chemical equilibrium