1.  Stages of processing. What are the three stages of triacylglycerol utilization? ✓ 1

2.  Control matters. Outline the control of triacylglycerol mobilization. ✓ 1

3.  Forms of energy. The partial reactions leading to the synthesis of acyl CoA (equations 1 and 2, Section 27.1) are freely reversible. The equilibrium constant for the sum of these reactions is close to 1, meaning that the energy levels of the reactants and products are about equal, even though a molecule of ATP has been hydrolyzed. Explain why these reactions are readily reversible. ✓ 1

4.  In its entirety. Write the complete reaction for fatty acid activation. ✓ 1

5.  Activation fee. The reaction for the activation of fatty acids before degradation is



This reaction is quite favorable because the equivalent of two molecules of ATP is hydrolyzed. Explain why, from a biochemical bookkeeping point of view, the equivalent of two molecules of ATP is used despite the fact that the left side of the equation has only one molecule of ATP. ✓ 1

6.  Repeating reactions. What are the recurring reactions of the oxidation of saturated fatty acids? ✓ 1

7.  Like Simon and Garfunkel. Match each term with its description. ✓ 1

8.  Proper sequence. Place the following list of reactions or relevant locations in the β oxidation of fatty acids in the proper order. ✓ 1

(a) Reaction with carnitine

(b) Fatty acid in the cytoplasm

(c) Activation of fatty acid by joining to CoA

(d) Hydration

(e) NAD⁺-linked oxidation

(f) Thiolysis

(g) Acyl CoA in mitochondrion

(h) FAD-linked oxidation

9.  Too tired to exercise. Explain why people with a hereditary deficiency of carnitine acyltransferase II have muscle weakness. Why are the symptoms more severe during fasting? ✓ 1

10.  A phantom acetyl CoA? In the equation for fatty acid degradation shown here, only seven molecules of CoA are required to yield eight molecules of acetyl CoA. How is this difference possible? ✓ 1

11.  Comparing yields. Compare the ATP yields from palmitic acid and palmitoleic acid. ✓ 1

12.  Counting ATPs 1. What is the ATP yield for the complete oxidation of C₁₇ (heptadecanoic) fatty acid? Assume that the propionyl CoA ultimately yields oxaloacetate in the citric acid cycle. ✓ 1

13.  Sweet temptation. Stearic acid is a C₁₈ fatty acid component of chocolate. Suppose you had a depressing day and decided to settle matters by gorging on chocolate. How much ATP would you derive from the complete oxidation of stearic acid to CO₂? ✓ 1

14.  Buff and lean. It has been suggested that if you are interested in losing body fat, the best time to do strenuous aerobic exercise is in the morning immediately after waking up; that is, after fasting. Don’t eat breakfast before exercising, but have a cup of caffeinated coffee. Caffeine is an inhibitor of cAMP phosphodiesterase. Explain why this suggestion might work biochemically. ✓ 1

15.  The best storage form. Compare the ATP yield from the complete oxidation of glucose, a six-carbon carbohydrate, and hexanoic acid, a six-carbon fatty acid. Hexanoic acid is also called caproic acid and is responsible for the “aroma” of goats. Why are fats better fuels than carbohydrates? ✓ 1

16.  From fatty acid to ketone body. Write a balanced equation for the conversion of stearate into acetoacetate. ✓ 2

17.  Generous, but not to a fault. Liver is the primary site of ketone-body synthesis. However, ketone bodies are not used by the liver but are released for other tissues to use. The liver does gain energy in the process of synthesizing and releasing ketone bodies. Calculate the number of molecules of ATP generated by the liver in the conversion of palmitate, a C-16 fatty acid, into acetoacetate. ✓ 2

18.  Counting ATPs 2. How much energy is attained with the complete oxidation of the ketone body d-3-hydroxybutyrate? ✓ 2

19.  Another view. Why might someone argue that the answer to problem 18 is wrong? (Consider the uses of succinyl CoA.) ✓ 2

20.  An accurate adage. An old biochemistry adage is that fats burn in the flame of carbohydrates. What is the molecular basis of this adage? ✓ 2

21.  Missing acyl CoA dehydrogenases. A number of genetic deficiencies in acyl CoA dehydrogenases have been described. A deficiency in acyl CoA dehydrogenase presents itself early in life or after a period of fasting. Symptoms include vomiting, lethargy, and, sometimes, coma. Not only are blood levels of glucose low (hypoglycemia), but also starvation-induced ketosis is absent. Provide a biochemical explanation for the last two observations.

22.  Missing ingredient. Why are liver cells not capable of using ketone bodies as a fuel? ✓ 2

23.  Finding triacylglycerols in all the wrong places. Insulin-dependent diabetes is often accompanied by high levels of triacylglycerols in the blood. Suggest a biochemical explanation for the high blood levels of triacylglycerols. ✓ 2

24.  Leaner times might follow. Why can’t animals convert fats into glucose? Why are plants capable of such a conversion?

25.  Losing protein. What is the purpose of protein degradation during the initial stages of starvation?

26.  Stop losing protein. How is the loss of muscle protein delayed during starvation?

27.  After lipolysis. During fatty acid mobilization, glycerol is produced. This glycerol is not wasted. Write a balanced equation for the conversion of glycerol into pyruvate. What enzymes are required in addition to those of the glycolytic pathway?

28.  Remembrance of reactions past. We encountered reactions similar to the oxidation, hydration, and oxidation reactions of fatty acid degradation earlier in our study of biochemistry. What other pathway employs this set of reactions?

29.  Ill-advised diet. Suppose that, for some bizarre reason, you decided to exist on a diet of whale and seal blubber, exclusively.

(a) How would a 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 dose of odd-chain fatty acids. Does your friend have your best interests at heart? Explain.

30.  Mutant enzyme. Carnitine palmitoyl transferase I (CPTI) catalyzes the conversion of long-chain acyl CoA into acyl carnitine, a prerequisite for transport into mitochondria and subsequent degradation. A mutant enzyme was constructed with a single amino acid change at position 3 of glutamic acid for alanine. Graphs A through C are based on data from studies performed to identify the effect of the mutation (data from J. Shi, H. Zhu, D. N. Arvidson, and G. J. Wodegiorgis, J. Biol. Chem. 274:9421–9426, 1999). ✓ 1



(a) What is the effect of the mutation on enzyme activity when the concentration of carnitine is varied? What are the K_M and V_max values for the wild-type (normal) and mutant enzymes?

(b) What is the effect when the experiment is repeated with varying concentrations of palmitoyl CoA? What are the K_M and V_max values for the wild-type and mutant enzymes?

(c) Graph C shows the inhibitory effect of malonyl CoA on the wild-type and mutant enzymes. Which enzyme is more sensitive to malonyl CoA inhibition? Note: Malonyl CoA is a substrate for fatty acid synthesis.

(d) Suppose that the concentration of palmitoyl CoA is 100 μM, that of carnitine is 100 μM, and that of malonyl CoA is 10 μM. Under these conditions, what is the most prominent effect of the mutation on the properties of the enzyme?

(e) What can you conclude about the role of glutamate 3 in carnitine acyltransferase I function?

31.  Refsum disease. Phytanic acid is a branched-chain fatty acid component of chlorophyll and is a significant component of milk. In susceptible people, phytanic acid can accumulate, leading to neurological problems. This syndrome is called Refsum disease or phytanic acid storage disease. ✓ 1



(a) Why does phytanic acid accumulate?

(b) What enzyme activity would you invent to prevent its accumulation?

32.  Sleight of hand. Animals cannot affect the net synthesis of glycogen from fatty acids. Yet, if animals are fed radioactive lipids (¹⁴C), over time, some radioactive glycogen appears. How is the appearance of radioactive glycogen possible in these animals?

33.  Necessary diversion. When acetyl CoA produced by β-oxidation exceeds the capacity of the citric acid cycle, ketone bodies are produced. Although acetyl CoA is not toxic, mitochondria must divert acetyl CoA to ketone bodies to keep functioning. Explain why. What would happen if ketone bodies were not generated?

34.  A hot diet. Tritium is a radioactive isotope of hydrogen and can be readily detected. Fully tritiated, six-carbon saturated fatty acid is administered to a rat, and a muscle biopsy of the rat is taken by concerned, sensitive, and discreet technical assistants. These assistants carefully isolate all of the acetyl CoA generated from the β oxidation of the radioactive fatty acid and remove the CoA to form acetate. What will be the overall tritium-to-carbon ratio of the isolated acetate? ✓ 1