1. Fundamentals of Biochemistry
Third Edition
Donald Voet • Judith G. Voet • Charlotte W. Pratt
Chapter 16
Glycogen Metabolism and Gluconeogenesis
Copyright © 2008 by John Wiley & Sons, Inc.

2. Chapter 16 Opener

3. Figure 16-1

4. Figure 16-2a

5. Figure 16-2b

6. A glycogen granule
Figure 16-2c

7. PLP is derived from vitamin B6; it’s a cofactor for phosphorylase
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8. PLP acts as an acid/base catalyst
Figure 16-3 part 1

9. C1-O1 bond cleaves
Figure 16-3 part 2

10. Formation of G1P
Figure 16-3 part 3

11. Active “crevice” of phosphorylase can accommodate 4 to 5 glucose units, so phosphorylase can’t get within 4 to 5 glucoses of a branch point
Figure 16-4

12. Intraconversion of G1P to G6P by phosphoglucomutase
Note the phosphorylated serine residue on enzyme
Figure 16-5

13. Emphasis on muscle and liver due to high glycogen content in both of those types of cells.
Box 16-2

14. Glycogen breakdown and synthesis
Note the coupling of reactions here is from the hydrolysis of PPi, not UTP
Figure 16-6

15. Nucleophilic attack of G1P phosphate frees PPi
Figure 16-7

16. Inhibits glycogen synthase due to similarity in shape to intermediate
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17. Figure 16-8

18. Figure 16-9

19. First, it increases the number of non-reducing ends
Why have branches?
First, it increases the number of non-reducing ends
Second, it reduces osmolarity of glucose
Box 16-3 figure 1

20. Why 2 branches per chain? With 3 branches, the outer edges are much too dense with branches for effective enzyme encounters.
Box 16-3 figure 2

21. Why 8 to 14 glucose units per branch
Why 8 to 14 glucose units per branch? Debranching is slow, so having to continually debranch slows the overall release of glucose.
Box 16-3 figure 3

22. Regulation involves several levels of control
Regulation involves several levels of control. This is a signal amplification effect.
Figure 16-10

23. Insulin and epinephrine are antagonists in metabolism.
Muscle
Insulin and epinephrine are antagonists in metabolism.
Figure 16-12

24. Muscle
Figure 16-13

25. Figure 16-14

26. Gluconeogenesis starts with all intermediates being converted to…
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27. As threatened, the committed steps in glycolysis (1, 3, 10) require a different pathway and different enzymes; the equilibrium steps have “reversible” enzymes.
Oxaloacetate is produced from pyruvate; note that there is no pathway from acetyl-CoA to pyruvate.
Figure 16-15

28. Pyruvate carboxylase has four subunits, each with a biotin prosthetic group.
Figure part 1

29. The biotin is bound to the enzyme through a lysine, and the biotin in turn bonds to carboxylate group (the one that is transferred to oxaloacetate) through a nitrogen in its ring.
Figure 16-17

30. Figure 16-18

31. Figure part 2

32. Figure 16-19

33. Note that using the malate route will result in changes to NAD+/NADH.
But, of course, oxaloacetate cannot be transported through the inner mitochondrial membrane directly (no carrier protein). Instead the malate-aspartate shuttle must be used.
Note that using the malate route will result in changes to NAD+/NADH.
Figure 16-20

34. Energy changes along the glycolytic and gluconeogenetic pathways’ committed steps (in kJ/mol).
Because these are substrate cycles, each arrow can be independently regulated for fine control.
Figure 16-21

35. Activates PFK; inhibits FBPase
As in many substrate cycles, a chemical will inhibit one pathway and activate the other
Activates PFK; inhibits FBPase
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36. Amusingly, in the liver, PFK and FBPase active sites are on the same protein (different domains).
When glucose is low, glucagon stimulates production of cAMP in liver cells, which activates PKA to phosphorylate PFK/FBPase at one serine residue – simultaneously activating one process and inhibiting the reverse.
Figure 16-22

37. Figure 16-23