1 SURVEY OF BIOCHEMISTRY Glycolysis

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

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 Drawing Glucose Draw the molecule glucose in the Haworth projection Start with the ring system

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

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 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 PGI Reaction Mechanism

9 Base Catalysis

10 PGI Reaction Mechanism Acid Catalysis

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

12 Practice Drawing Fructose 6-Phosphate Begin with the ring system

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

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

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

18 Aldolase Rxn Mechanism

19 Aldolase Rxn Mechanism

20 Aldolase Rxn Mechanism

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

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

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