1.
10. Fats into glucose? Fats are usually metabolized into acetyl CoA and then
further processed through the citric acid cycle. In Chapter 16, we learned that
glucose could be synthesized from oxaloacetate, a citric acid cycle intermediate.
Why, then, after a long bout of exercise depletes our carbohydrate stores, do we
need to replenish those stores by eating carbohydrates? Why do we not simply
replace them by converting fats into carbohydrates?
Answer
We cannot get the net conversion of fats into glucose because the only means to
get the carbons from fats into oxaloacetate, the precursorto glucose, is through the
citric acid cycle. However, although two carbon atoms enter the cycle as acetyl
CoA, two carbon atoms are lost as CO2 before oxaloacetate is formed. Thus,
although some carbon atoms from fats may end up as carbonatoms in glucose, we
cannot obtain a net synthesis of glucose from fats.
See question
2.(a) Which enzymes are required to get net synthesis of oxaloacetate from acetyl
CoA?
(b) Write a balanced equation for the net synthesis.
(c) Do mammalian cells contain the requisite enzymes?
Answer
(a) Isocitrate lyase and malate synthase are required in addition to the enzymes of
the citric acid cycle.
(b) 2 Acetyl CoA + 2 NAD+ + FAD + 3 H2O →oxaloacetate + 2 CoA + 2 NADH
+ FADH2 + 3 H+
(c) No. Hence, mammals cannot carry out the net synthesis of oxaloacetate from
acetyl CoA.
4. Acting catalytically. The citric acid cycle itself, which is composed of
enzymatically catalyzed steps, can be thought of essentially as the productof a
supramolecular enzyme. Explain.
Answer
Enzymes or enzyme complexes are biological catalysts. Recall that a catalyst
facilitates a chemical reaction without the catalyst itself being permanently altered.
Oxaloacetate can be thought of as a catalyst because it binds to an acetyl group,
leads to the oxidative decarboxylation of the two carbon atoms, and is regenerated

2.
at the completion of a cycle. In essence, oxaloacetate (and any cycle intermediate)
acts as a catalyst.
9. Synthesizing α-ketoglutarate. It is possible, with the use of the reactions and
enzymes discussed in this chapter, to convert pyruvate into α -ketoglutarate
without depleting any of the citric acid cycle components. Write a balanced
reaction scheme for this conversion, showing cofactors and identifying the required
enzymes.
Answer:
1. After lipolysis. Write a balanced equation for the conversion of glycerol into
pyruvate. Which enzymes are required in addition to those of the glycolytic
pathway?
Answer
Glycerol + 2 NAD+ + Pi + ADP →pyruvate + ATP + H2O + 2 NADH + H+
Glycerol kinase and glycerol phosphatedehydrogenase.

3.
2. From fatty acid to ketone body. Write a balanced equation for the conversion of
stearate into acetoacetate.
Answer
Stearate + ATP + 13 1/2 H2O + 8 FAD + 8 NAD+ 4 1/2 →acetoacetate + 14 1/2
H+ + 8 FADH2 + 8 NADH + AMP + 2 Pi
5. Tracing carbons. Consider a cell extract that actively synthesizes palmitate.
Supposethat a fatty acid synthase in this preparation forms one molecule of
palmitate in about 5 minutes. A large amount of malonyl CoA labeled with 14C in
each carbonof its malonyl unit is suddenly added to this system, and fatty acid
synthesis is stopped a minute later by altering the pH. The fatty acids in the
supernatant are analyzed for radioactivity. Which carbonatom of the palmitate
formed by this system is more radioactive C-1 or C-14?
Answer:
C-1 is more radioactive.
7. Kinasesurfeit. Supposethat a promoter mutation leads to the overproduction of
protein kinase A in adipose cells.
How might fatty acid metabolism be altered by this mutation?
Answer
Adipose-cell lipase is activated by phosphorylation. Hence, overproductionof the
cAMP-activated kinase will lead to an accelerated breakdown of triacylglycerols
and a depletion of fat stores.
17. Ill-advised diet. Supposethat, for some bizarre reason, you decided to exist on
a diet of whale and seal blubber, exclusively.
(a) How would lack of carbohydrates affect your ability to utilize fats?
(b) What would your breath smell like?
(c) One of your best friends, after trying unsuccessfully to convince you to
abandon this diet, makes you promise to consume a healthy doseof odd-chain fatty
acids. Does your friend have your best interests at heart? Explain.
Answer

4.
(a) Fats burn in the flame of carbohydrates. Without carbohydrates, there would be
no anapleurotic reactions to replenish the TCA-cycle components. With a diet of
fats only, the acetyl CoA from fatty acid degradation would build up.
(b) Acetone from ketone bodies.
(c) Yes. Odd-chain fatty acids would lead to the production of propionyl CoA,
which can be converted into succinyl CoA, a TCA-cycle component. It would
serve to replenish the TCA cycle and mitigate the halitosis.
8. Distinctive sugars. The intravenous infusion of fructose into healthy volunteers
leads to a two- to fivefold increase in the level of lactate in the blood, a far greater
increase than that observed after the infusion of the same amount of glucose.
(a) Why is glycolysis more rapid after the infusion of fructose?
(b) Fructosehas been used in place of glucose for intravenous feeding. Why is this
use of fructose unwise?
Answer
(a) The fructose 1-phosphate pathway forms glyceraldehyde 3-phosphate.
(b) Phosphofructokinase, a key control enzyme, is bypassed. Furthermore, fructose
1-phosphate stimulates pyruvate kinase
9. Metabolic mutants. Predict the effect of each of the following mutations on the
pace of glycolysis in liver cells:
(a) Loss of the allosteric site for ATP in phosphofructokinase.
(b) Loss of the binding site for citrate in phosphofructokinase.
(c) Loss of the phosphatasedomain of the bifunctional enzyme that controls the
level of fructose 2,6-bisphosphate.
(d) Loss of the binding site for fructose 1,6-bisphosphatein pyruvate kinase.
Answer
(a) Increased; (b) increased; (c) increased; (d) decreased.
10. Metabolic mutant. What are the likely consequences ofa genetic disorder
rendering fructose 1,6-bisphosphatasein liver less sensitive to regulation by
fructose 2,6-bisphosphate?
Answer
Fructose2,6-bisphosphate, present at high concentration when glucose is abundant,
normally inhibits gluconeogenesis by blocking fructose 1,6-bisphosphatase. In this
genetic disorder, the phosphataseis active irrespective of the glucose level. Hence,

5.
substrate cycling is increased. The level of fructose1,6-bisphosphate is
consequently lower than normal. Less pyruvate is formed and thus less ATP is
generated.
12. Tracing carbon atoms II. If cells synthesizing glucose from lactate are exposed
to CO2 labeled with 14C, what will be the distribution of label in the newly
synthesized glucose?
Answer
There will be no labeled carbons. The CO2 added to pyruvate (formed from the
lactate) to form oxaloacetate is lost with the conversion of oxaloacetate into
phosphoenolpyruvate.
3. A versatile building block. (a) Write a balanced equation for the conversion of
aspartate into glucose through the intermediate oxaloacetate. Which coenzymes
participate in this transformation? (b) Write a balanced equation for the conversion
of aspartate into oxaloacetate through the intermediate fumarate.
Answer
(a) -ketoglutarate + GTP + ATP + 2 H2O + NADH + H+ 1/2→
glucose + glutamate + CO2 + ADP + GDP + NAD+ + 2 Pi
The required coenzymes are pyridoxal phosphatein the transamination reaction
and NAD+/NADH in the redox reactions.
(b) Aspartate + CO2 + NH4+ + 3 ATP + NAD+ + 4 H2O →oxaloacetate + urea +
2 ADP + 4 Pi + AMP + NADH +H+
8. Completing the cycle. Four high-transfer-potential phosphorylgroups are
consumed in synthesizing urea according to the stoichiometry given in Section
23.4.2. In this reaction, aspartate is converted into fumarate. Supposethat fumarate
is converted back into aspartate. What is the resulting stoichiometry of urea
synthesis? How many hightransfer- potential phosphorylgroups are spent?
Answer
CO2 + NH4+ + 3 ATP + NAD+ + aspartate + 3 H2O →urea + 2 ADP + 2 Pi +
AMP + PPi + NADH + H+ + oxaloacetate
Four high-transfer-potential groups are spent.

6.
10. Ammonia toxicity. Glutamate is an important neurotransmitter whose levels
must be carefully regulated in the brain. Explain how a high concentration of
ammonia might disrupt this regulation. How might a high concentration of
ammonia alter the citric acid cycle?
Answer
-ketoglutarate, producing a high
concentration of glutamate in an unregulat -Ketoglutarate for
glutamate synthesis could be removed from the citric acid cycle, thereby
diminishing the cell's respiration capacity.
18. Fuel choice. Within a few days after a fast begins, nitrogen excretion
accelerates to a higher-than-normal level.
After a few weeks, the rate of nitrogen excretion falls to a lower level and
continues at this low rate. However, after the fat stores have been depleted,
nitrogen excretion rises to a high level.
(a) What events trigger the initial surge of nitrogen excretion?
(b) Why does nitrogen excretion fall after several weeks of fasting?
(c) Explain the increase in nitrogen excretion when the lipid stores have been
depleted.
Answer
(a) Depletion of glycogen stores. When they are gone, proteins must be degraded
to meet the glucose needs of the brain. The resulting amino acids are deaminated,
and the nitrogen atoms are excreted as urea.
(b) The brain has adapted to the use of ketone bodies, which are derived from fatty
acid catabolism. In other words, the brain is being powered by fatty acid
breakdown.
(c) When the glycogen and lipid stores are gone, the only available energy source
is protein.