1. Chapter 14.1 and 14.2: Glycolysis and Feeder Pathways
CHEM 7784
Biochemistry
Professor Bensley

2. CHAPTER 14.1 and 14.2 Glycolysis
Today’s Objectives: To learn and understand the
Process of harnessing energy from glucose via glycolysis
Various pathways by which carbohydrates other than glucose enter glycolysis

3. Central Importance of Glucose
Glucose is an excellent fuel
Glucose is a versatile biochemical precursor
Four major pathways of glucose utilization
FIGURE 14-1 Major pathways of glucose utilization. Although not the only possible fates for glucose, these four pathways are the most significant in terms of the amount of glucose that flows through them in most cells.

4. Glycolysis: The Big Picture
Anaerobic process carried out by all cells but at different rates
Converts hexose to two pyruvates
Generates 2 ATP and 2 NADH
For certain cells in the brain and eye, glycolysis is the only ATP generating pathway
Glucose + 2 ADP + 2 NAD+ + 2Pi 
2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2H20

5. Glycolysis: Importance
Glycolysis is a sequence of ten enzyme-catalyzed reactions by which glucose is converted into pyruvate
Two phases:
First phase converts glucose to two G-3-P
Second phase produces two pyruvate molecules
Three possible fates for pyruvate

6. Glycolysis: The Preparatory Phase
FIGURE 14-2a The two phases of glycolysis. For each molecule of glucose that passes through the preparatory phase (a), two molecules of glyceraldehyde 3-phosphate are formed; both pass through the payoff phase (b). Pyruvate is the end product of the second phase of glycolysis. For each glucose molecule, two ATP are consumed in the preparatory phase and four ATP are produced in the payoff phase, giving a net yield of two ATP per molecule of glucose converted to pyruvate. The numbered reaction steps are catalyzed by the enzymes listed on the right, and also correspond to the numbered headings in the text discussion. Keep in mind that each phosphoryl group, represented here as P, has two negative charges (—PO32–).

7. Glycolysis: The Payoff Phase
FIGURE 14-2b The two phases of glycolysis. For each molecule of glucose that passes through the preparatory phase (a), two molecules of glyceraldehyde 3-phosphate are formed; both pass through the payoff phase (b). Pyruvate is the end product of the second phase of glycolysis. For each glucose molecule, two ATP are consumed in the preparatory phase and four ATP are produced in the payoff phase, giving a net yield of two ATP per molecule of glucose converted to pyruvate. The numbered reaction steps are catalyzed by the enzymes listed on the right, and also correspond to the numbered headings in the text discussion. Keep in mind that each phosphoryl group, represented here as P, has two negative charges (—PO32–).

8. STEP 1 - The Hexokinase Reaction
The first step, phosphorylation of glucose, is catalyzed by hexokinase in eukaryotes, and by glucokinase in prokaryotes
This process uses the energy of ATP

9. STEP 2 - Phosphohexose Isomerization
An aldose can isomerize into ketose via an enediol intermediate
Overall – Glucose-6-Phosphate is converted to Fructose-6-Phosphate

10. FIGURE 14-4 (part 1) The phosphohexose isomerase reaction
FIGURE 14-4 (part 1) The phosphohexose isomerase reaction. The ring opening and closing reactions (steps 1 and 4) are catalyzed by an active-site His residue, by mechanisms omitted here for simplicity. The proton (pink) initially at C-2 is made more easily abstractable by electron withdrawal by the adjacent carbonyl and nearby hydroxyl group. After its transfer from C-2 to the active-site Glu residue (a weak acid), the proton is freely exchanged with the surrounding solution; that is, the proton abstracted from C-2 in step 2 is not necessarily the same one that is added to C-1 in step 3.

11. FIGURE 14-4 (part 2) The phosphohexose isomerase reaction
FIGURE 14-4 (part 2) The phosphohexose isomerase reaction. The ring opening and closing reactions (steps 1 and 4) are catalyzed by an active-site His residue, by mechanisms omitted here for simplicity. The proton (pink) initially at C-2 is made more easily abstractable by electron withdrawal by the adjacent carbonyl and nearby hydroxyl group. After its transfer from C-2 to the active-site Glu residue (a weak acid), the proton is freely exchanged with the surrounding solution; that is, the proton abstracted from C-2 in step 2 is not necessarily the same one that is added to C-1 in step 3.

12. STEP 3 - The Second Priming Reaction; The First Commitment
This is an irreversible step
The product, fructose 1,6-bisphosphate is committed to become pyruvate and yield energy

13. STEP 4 - Aldolases Cleave 6-Carbon Sugars
Step four is the cleavage of Fructose 1,6-Bisphosphate

14. FIGURE 14-5 (part 1) The class I aldolase reaction
FIGURE 14-5 (part 1) The class I aldolase reaction. The reaction shown here is the reverse of an aldol condensation. Note that cleavage between C-3 and C-4 depends on the presence of the carbonyl group at C-2. A and B represent amino acid residues that serve as general acid (A) or base (B).

15. FIGURE 14-5 (part 2) The class I aldolase reaction
FIGURE 14-5 (part 2) The class I aldolase reaction. The reaction shown here is the reverse of an aldol condensation. Note that cleavage between C-3 and C-4 depends on the presence of the carbonyl group at C-2. A and B represent amino acid residues that serve as general acid (A) or base (B).

16. FIGURE 14-5 (part 3) The class I aldolase reaction
FIGURE 14-5 (part 3) The class I aldolase reaction. The reaction shown here is the reverse of an aldol condensation. Note that cleavage between C-3 and C-4 depends on the presence of the carbonyl group at C-2. A and B represent amino acid residues that serve as general acid (A) or base (B).

17. FIGURE 14-5 (part 4) The class I aldolase reaction
FIGURE 14-5 (part 4) The class I aldolase reaction. The reaction shown here is the reverse of an aldol condensation. Note that cleavage between C-3 and C-4 depends on the presence of the carbonyl group at C-2. A and B represent amino acid residues that serve as general acid (A) or base (B).

18. FIGURE 14-5 (part 5) The class I aldolase reaction
FIGURE 14-5 (part 5) The class I aldolase reaction. The reaction shown here is the reverse of an aldol condensation. Note that cleavage between C-3 and C-4 depends on the presence of the carbonyl group at C-2. A and B represent amino acid residues that serve as general acid (A) or base (B).

19. STEP 5 - Triose Phosphate Interconversion
DAP is converted enzymatically to GAP

20. STEP 6 - Glyceraldehyde 3-Phosphate Dehydrogenase Reaction
First step in the “Payoff Phase” of Glycolysis
First energy-yielding step in glycolysis

21. FIGURE 14-7 (part 1) The glyceraldehyde 3-phosphate dehydrogenase reaction.

22. FIGURE 14-7 (part 2) The glyceraldehyde 3-phosphate dehydrogenase reaction.

23. FIGURE 14-7 (part 3) The glyceraldehyde 3-phosphate dehydrogenase reaction.

24. FIGURE 14-7 (part 4) The glyceraldehyde 3-phosphate dehydrogenase reaction.

25. FIGURE 14-7 (part 5) The glyceraldehyde 3-phosphate dehydrogenase reaction.

26. STEP 7 - First Substrate-Level Phosphorylation
1,3-bisphosphoglycerate is a high-energy compound that can donate the phosphate group to ADP to make ATP

27. STEP 8 - Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
This is a reversible isomerization reaction

28. Mechanism of the Phosphoglycerate Mutase Reaction
FIGURE 14-8 (part 1) The phosphoglycerate mutase reaction.

29. FIGURE 14-8 (part 2) The phosphoglycerate mutase reaction.

30. STEP 9 - Dehydration of 2-Phosphoglycerate
The goal here is to create a better phosphoryl donor
Loss of phosphate from 2-phosphoglycerate would merely give a secondary alcohol with no further stabilization …

31. STEP 10 - Second Substrate-Level Phosphorylation
… but loss of phosphate from phosphoenolpyruvate yields an enol that tautomerizes into ketone

33. Feeder Pathways for Glycolysis
FIGURE Entry of dietary glycogen, starch, disaccharides, and hexoses into the preparatory stage of glycolysis.