Download BCHM 463 Supplemental Problems for Friday, April 9, 2004 1. a

BCHM 463
Supplemental Problems for Friday, April 9, 2004
1. a) What is the net reaction for gluconeogenesis?
2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 4 H2O → Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ + 2 H+
b) What is the net reaction for gluconeogenesis + glycolysis?
2 ATP + 4 H2O + 2 GTP → 2 ADP + 4 Pi + 2 GDP + 4 H+
2. Which steps of the gluconeogenesis pathway are shared by enzymes in the glycolysis
pathway?
Steps 2, 4, 5, 6, 7, 8, and 9
Write out the four chemical reactions in gluconeogenesis that allow bypass of the
three metabolically irreversible steps in glycolysis.
Pyruvate carboxylase:
Pyruvate + HCO3- + ATP → oxaloacetate + ADP + Pi + H+
Phosphoenolpyruvate carboxylase:
Oxaloacetate + GTP → phosphoenolpyruvate + CO2 + GDP
Fructose bisphosphatase:
Fructose-1,6-bisphosphate + H2O → Fructose-6-phosphate + Pi
Glucose-6-phosphatase:
Glucose-6-phosphate + H2O → Glucose + Pi
3. What is the primary function of the pentose phosphate pathway?
Produces NADPH
4. Write a balanced equation for the pentose phosphate pathway including structures of
starting material and products.
3 G6P + 6 NADP+ + 3 H2O → 6 NADPH + 6 H+ + 3 CO2 + 2 F6P + GAP
O
O
OPO3-2
O
HO
HO
OH
G6P
OH
O
O
-O P
HO
O
O P
-O
O
O
N+
O
OH
NH2
N
N
N
N
OPO3-2
NH2
NH2
O
O
P
-O
HO
O
O P
-O
O
O
OH
O
N
O
HO
OH
OH
NH2
N
N
F6P
N
N
O
HO
OPO3
-2
HO
OPO3-2
-2O PO
3
H
OH
NADP+
NADPH
GAP
BCHM 463
Supplemental Problems for Friday, April 9, 2004
5. What are the two key enzymes involved in glycogen metabolism and how are they
regulated by phosphorylation?
Glycogen synthase and glycogen phosphorylase (see Figs. 15-12 and 15-13 for detailed description of
regulation through phosphorylation.)
What is the effect of epinephrine on the regulation of these enzymes and how does this
affect glycogen levels?
Epinephrine starts a cascade of phosphorylation events which lead to breakdown of glycogen into Glucose1-phosphate for use in glycolysis. In other words, glycogen phosphorylase is phosphorylated and enters its
“active” state.
6. Write the net reaction, including structures, of the two steps that produce NADPH in
the pentose phosphate pathway.
OPO3-2
OPO3-2
HO
HO
G6P DH
O
HO
HO
Mg++
OH
OH
O
OH
NADP+
CO2
NADPH
6-phosphogluconate
dehydrogenase
OH OH
-2O PO
3
O
-
Mg++
3PO
OH O
OH OH
NADP+
OH OH
-2O
NADPH
What is the significance of CO2 release in this pathway?
This is a major driving force for the reaction.
7. Compare the relative efficiencies (in ATP’s per glucose oxidized) of glucose
oxidation via glycolysis + the citric acid cycle vs. glucose oxidation via the pentose
phosphate pathway + glycolysis. (Assume that NADH and NADPH are each
equivalent to three ATPs and that FADH is equivalent to 2 ATPs.)
Oxidation through glycolysis and the citric acid cycle yields ~38 ATP’s per molecule of glucose. The other
pathway yields, assuming that it continues through the citric acid cycle, 37 ATPs per molecule of glucose.
8. Like glycolysis, the citric acid cycle is regulated by controlling the enzyme activities
of 3 enzymes. a) Name these enzymes and give all species that inhibit (negatively
modulate) the enzymes’ activities.
Citrate synthase, isocitrate dehydrogenase, and ∝-ketoglutarate dehydrogenase are the control points for the
citric acid cycle. See figure 16-14 for the intermediates and products which inhibit the citric acid cycle.
BCHM 463
Supplemental Problems for Friday, April 9, 2004
b) Rationalize the use of these enzymes as control points (i.e. Why are these enzymes
able to serve as control points?)?
These enzymes function far from equilibrium (i.e. have large negative ∆G) and can therefore serve as
control points for flux through this pathway.
c) Are there other enzymes that might be able to serve as control points in the citric acid
cycle?
No, for all the other enzymes, ∆G is approximately 0.
9. Write a balanced equation for the citric acid cycle.
3 NAD+ + FAD + GDP + Pi + acetyl-CoA + 2 H2O → 3 NADH + FADH2 + GTP + CoA + 2 CO2 + 3 H+
10. From which citric acid cycle intermediate are each of the following amino acids
derived?
a) aspartate: oxaloacetate
b) glutamate: ∝-ketoglutarate