Biosc

1000

Lecture 17 Sample Problem Answers

1. Malonyl CoA, labeled with 14C in the methylene carbon, is used in excess as a
substrate in vivo for the synthesis of palmitoyl CoA, which is catalyzed by a
yeast fatty acid synthase complex. Acetyl CoA and other substrates are also
present in the system, but acetyl CoA carboxylase is not. Which carbons in
palmitoyl CoA will be labeled?

The methylene C in malonyl CoA is the CH2group. AcetylACP and malonylACP
condense to form acetoacetylACP. Carbons 4 and 3 of acetoacetylACP are not
labeled because they are derived from acetyl CoA. These two carbons will
become carbons 15 and 16 of palmitate. Only C2 of acetoacetylACP will be
labeled because it is derived from the methylene carbon of malonyl ACP. When
the second round of synthesis begins, butyrylACP condenses with a second
molecule of methylene-labeled malonylACP, which contributes C1 and C2 to the
newly formed six carbon ACP intermediate. In this compound, C2 and C4 will be
labeled. Chain elongation continues until palmitoylACP is formed. Each even
numbered carbon will be labeled, except for C16 at the end.

2. Glucagon has been shown to reduce the activity of HMG CoA reductase, the
enzyme that catalyzes the committed step in cholesterol biosnthesis. Why is
this observation consistent with the overall effect of glucagon on cellular
metabolism?

The presence of glucagon is a signal that carbohydrate and triacylglycerol
catabolism is needed to generate energy for the organism. Under such
conditions, one would expect biosynthetic reactions, including the synthesis of
cholesterol, to be suppressed because energy charge is low. (HMG CoA
reductase is actually inhibited by phosphorylation by an AMP-dependent kinase
when AMP levels are high but that is beyond the scope of what you are
expected to know.)

3. People who have elevated levels of low-density lipoproteins (LDL) in their
serum are frequently first treated by restriction of dietary intake of
cholesterol. The drug lovastatin, a competitive inhibitor of HMG CoA
reductase, is also a frequently used treatment. How does each of these
treatments reduce serum LDL levels?

Restricting the level of dietary cholesterol lowers the input of exogenous
cholesterol into lipoproteins, so fewer LDL molecules are present in the serum.

Lovastatin will suppress de novo cholesterol biosynthesis. This stimulates the
uptake of LDL from the bloodstream.

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Biosc 1000

4. Why is it more efficient to store energy as lipid rather than as glycogen?

First, the energy yield per gram of lipid (about 38 kJ/g) is more than twice that for
carbohydrate (about 17 kJ/g). Second, lipid is stored as anhydrous lipid droplets, but
carbohydrates such as glycogen and starch are stored hydrated, and the water of
hydration roughly triples the effective weight of the carbohydrate, reducing the energy
yield to about 6 kJ/g.

5. Calculate the approximate yield in ATP molecules of the complete oxidation
of hexanoic acid (6:0).

After activation of hexanoic acid to hexanoyl CoA, two rounds of oxidation
are required to produce 3 acetyl CoA molecules, which are completely oxidized
by the CAC.

Oxidation(2 rounds) yields 2 NADH and 2 FADH2
Citric acid cycle (3 times) yields 9 NADH, 3 FADH2, 3 GTP

Each molecule of NADH makes 2.5 ATP
Each molecule of FADH2 makes 1.5 ATP

11 NADH
27.5 ATP
5 FADH2

7.5 ATP
3 GTP

3 ATP
38 ATP
activation
2 ATP
Total

36 ATP

6. Indicate whether the following statement is true or false and explain your
answer: After a meal rich in carbohydrates, acetyl CoA levels rise and ketone
body synthesis increases.

False. When carbohydrates are abundant, oxaloacetate levels are high and
condensation of acetyl CoA and oxaloacetate produces citrate. Citrate is used
for energy production (CAC) as well as for fatty acid synthesis. Ketone bodies
are produced when acetyl CoA is abundant but oxaloacetate is depleted.

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