1. 1 SURVEY OF BIOCHEMISTRY Glycolysis

2. 2 Glycolysis Overview Glycolysis: breakdown of glucose into pyruvate with net production of ATP Occurs in cytosol Glucose + 2 ADP + 2 NAD + + 2 P i 2 Pyruvate + 2 ATP + 2 NADH + 2 H + 10 steps

3. 3 Glycolysis: First 5 Steps Convert Glucose into G6P Convert G6P into F6P Convert F6P into FBP Split FBP into two molecules –GAP: ready for next step –DHAP: must convert into GAP before proceeding

4. 4 Drawing Glucose Draw the molecule glucose in the Haworth projection Start with the ring system 1 23 4 5

5. 5 Drawing Glucose Draw the molecule glucose in the Haworth projection Start with the ring system Add the substituents on the ring system C1 - draw OH down C2 - draw OH down C3 - draw OH up C4 - draw OH down C5 - draw CH 2 OH up 1 2 3 4 5 6

6. 6 Glycolysis: Step #1 Kinases transfer PO 3 2- groups from one molecule to another Hexokinase Mg 2+ Reaction mostly proceeds to the right

7. 7 Glycolysis: Step #2 Phosphoglucose Isomerase (PGI) converts G6P into a fructose-based molecule through acid-base catalysis Let’s look at this mechanism more closely…

8. 8 PGI Reaction Mechanism

9. 9 Base Catalysis

10. 10 PGI Reaction Mechanism Acid Catalysis

11. 11 PGI Reaction Mechanism H+H+ Base catalyzes ring closure

12. 12 Practice Drawing Fructose 6-Phosphate Begin with the ring system 2 3 4 1 5 6

13. 13 Practice Drawing Fructose 6-Phosphate Add Substitutents C1 = CH 2 OH drawn up C2 - draw OH down C3 - draw OH up C4 - draw OH down C6 = CH 2 OPO 3 2- drawn up Begin with the ring system 2 3 4 1 5 6

14. 14 Glycolysis: Step #3 PFK + ADP + H + Phosphofructokinase transfers PO 3 2- group from ATP to fructose-6-phosphate So far, 2 ATP molecules have been invested in glycolysis!

15. 15 Drawing FBP Recall from Ch. 8 Haworth and Fischer projections are equivalent

16. 16 Glycolysis: Step #4 Aldolase Aldolase is unique in glycolysis; it cleaves FBP into two 3-C molecules - GAP and DHAP Let’s see how aldolase works…

17. 17 Aldolase Rxn Mechanism Aldolase binds to the substrate Fructose-1,6-Bisphosphate

18. 18 Aldolase Rxn Mechanism

19. 19 Aldolase Rxn Mechanism

20. 20 Aldolase Rxn Mechanism

21. 21 Aldolase Rxn Mechanism H2OH2O Aldolase cleaves FBP into GAP and DHAP

22. 22 Glycolysis: Step #5 Triose Phosphate Isomerase DHAP must be converted into GAP via the enzyme triose phosphate isomerase (TIM) to proceed through glycolysis

23. 23 Overview After Step 5 Two molecules of ATP are invested initially. One molecule of glucose gets metabolized into 2 molecules of GAP

24. 24 Next Week… Steps #6-10 of glycolysis Overview of bioenergetics from glycolysis More on enzymes in glycolysis