1. Bioenergetics and Glycolysis Getting the E out of C

2. Overall Chemical Reaction For all of Cellular Respiration C 6 H 12 O 6 + 6 O 2 ---  6 CO 2 + 6 H 2 O Overall free energy = 687 kcal/mol or 3.8 kcal/g Not really that efficient (Stay tuned for the actual)

3. Energy Transfer follows thermodynamic laws Gibbs helmholtz ΔG = ΔH – TΔS Enthalpy Entropy –Remember ΔS universe > 0 is a spontaneous process Overall if ΔG < 0 the process is spontaneous ΔG = -RTlnK –Relates ΔG to equilibrium ΔG are additive State function Overall ΔG has to be – for a process to be spontaneous

4. Le Chatelier’s Principle and ΔG Remember Le Chatelier and affect on equilibrium –If one reaction has a positive ΔG, but the next reaction, which is in equilibrium has a negative ΔG, the first reaction can be pulled through –Many examples of this in glycolysis

5. ATP (Adenosine Tri-Phosphate)

6. Hydrolysis of ATP ATP ------  ADP + Pi + 7.3 kcal

7. Energy from ATP hydrolysis 7.3 kcal /mol (30.5 kJ/mol for you SI nuts) Energy from: –Separation of negative charges –Increased entropy Phosphate now free…2 things instead of one –Resonance stabilization of phosphate

8. Other Energy sources Hydrolysis of thioester –Resonance stabilization of carboxylate –Energy released from group transfer, not simply hydrolysis –Coenzyme A (CoA) is an important thiol that forms thioesters

9. Coenzyme A

10. Redox Review: –Electron transfer reactions –Energy from electron transfer –Electrons typically transferred to a carrier NAD + + 2 e - + 2H + -  NADH + H + FAD + 2 e - + 2H + -  FADH 2 Electrons transferred later for ATP generation

11. NAD (Nicotinamide Adenine Dinucleotide)

12. Reduction of NAD + on Nicotinamide Ring

13. FAD (Flavin Adenine Dinucleotide)

14. Reduction of Flavin Ring on FAD

15. Glycolysis In Cytosol Anaerobic Breakdown of glucose to two pyruvate molecules –Glucose + 2 ADP + 2 Pi + 2 NAD + -  2 pyruvate + 2 ATP + 2 NADH + 2 H + –C 6 H 12 O 6 + 2 ADP + 2 Pi + 2 NAD + -  2 C 3 H 3 O 3 - + 2 ATP + 2 NADH + 2 H +

16. Glycolysis

17. Hexokinase reaction Irreversible Kinase (phosphate transfer) -16.7kJ

18. Hexose phosphate isomerase reaction Keto-aldol isomerization –Glucose to fructose 1.7 kJ

19. Phosphofructokinase reaction Same as hexokinase reaction -14.2kJ Major point of regulation –Committed step –Stimulated by ADP and AMP –Inhibited by ATP and fatty acids

20. Aldolase Reaction Reverse aldol condensation 23.8kJ Makes 2 3-Carbon molecules

21. Triose phosphate isomerase Keto-enol isomerization (like hexose phosphate isomerase reaction) 7.5kJ Net is 2 glyceraldehyde – 3 – phosphate From now on each reaction times 2

22. Glyceraldehyde -3-phosphate dehydrogenase Oxidation coupled to phosphorylation Makes NADH 6.3kJ (remember X 2)

23. Phosphoglycerate Kinase Phosphate transfer –Substrate level phosphorylation Driven by stabilization of carboxylate -18.5kJ Pulls previous reactions through

24. Phosphoglycerate mutase Moves from 3 -  2 2 steps –Makes 2,3 –Removes 3 4.4kJ

25. enolase Makes unstable enol intermediate 7.5 kJ

26. Pyruvate kinase Last reaction….woohoo Substrate level phosphorylation Stabilization of enol -  keto -31.4kJ

27. Net products from Glycolysis (per glucose) 2 pyruvate 2 NADH 2 ATP Total energy = -61.3 kJ –Sum of energies

28. Fates of pyruvate

29. Fates of Pyruvate Depend on organism and conditions Yeast –Anaerobic Pyruvate decarboxylase Makes alcohol –Aerobic Makes acetyl CoA ---  energy or fat Others –Anaerobic LDH Makes lactate Sore muscles –Aerobic Acetyl Co A ---  energy or fat

30. Glycogen

31. Glycogenolysis

32. Glycogen breakdown Glycogen phosphorylase breaks down alpha 1,4 linkages –Makes glucose-1-phosphate –Enzyme changes to glucose-6-phosphate and enters glycolysis there Can’t break 1,6 linkages –Debranching enzyme breaks 1,6 (when 4 sugars away from branch) and adds to end –Glycogen phosphorylase takes over and breaks down the rest

33. Other sugars Fructose –Comes in at fructose-6-p and immediately phosphorylated Lipogenic…after branch to glycogen…makes acetyl CoA Lactose –Glucose and galactose Galactose –Epimerase turns into glucose-6-P and enters there

34. gluconeogenesis Making glucose from pyruvate –In liver –Uses same enzymes as glycolysis except where nonequilibrium reactions –Uses NADPH instead of NADH