Match’em. Match each term with its description.

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?

Forms of energy. The partial reactions leading to the synthesis of acyl CoA (equations 1 and 2, in Section 22.2) 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.

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.

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

Remembrance of reactions past. We have 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?

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?

Comparing yields. Compare the ATP yields from palmitic acid and palmitoleic acid.

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.

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?

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 caprioic acid and is responsible for the “aroma” of goats. Why are fats better fuels than carbohydrates?

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

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 C₁₆ fatty acid, into acetoacetate.

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

Another view. Why might someone argue that the answer to problem 14 is wrong?

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

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.

A hot diet. Tritium is a radioactive isotope of hydrogen and can be readily detected. A 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 discrete 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?

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.

Match ’em. Match the terms with the descriptions.

Counterpoint. Compare and contrast fatty acid oxidation and synthesis with respect to

The fizz in fatty acid synthesis. During the initial in vitro studies on fatty acid synthesis, experiments were performed to determine which buffer would result in optimal activity. Bicarbonate buffer proved far superior to phosphate buffer. The researchers could not initially account for this result. From your perspective of many decades later, explain why the result is not surprising.

A supple synthesis. Myristate, a saturated C₁₄ fatty acid, is used as an emollient for cosmetics and topical medicinal preparations. Write a balanced equation for the synthesis of myristate.

The cost of cleanliness. Lauric acid is a 12-carbon fatty acid with no double bonds. The sodium salt of lauric acid (sodium laurate) is a common detergent used in a variety of products, including laundry detergent, shampoo, and toothpaste. How many molecules of ATP and NADPH are required to synthesize lauric acid?

Proper organization. Arrange the following steps in fatty acid synthesis in their proper order.

No access to assets. What would be the effect on fatty acid synthesis of a mutation in ATP-citrate lyase that reduces the enzyme’s activity? Explain.

The truth and nothing but. True or False. If false, explain.

Odd fat out. Suggest how fatty acids with odd numbers of carbons are synthesized.

Labels. Suppose that you had an in vitro fatty acid-synthesizing system that had all of the enzymes and cofactors required for fatty acid synthesis except for acetyl CoA. To this system, you added acetyl CoA that contained radioactive hydrogen (³H, tritium) and carbon 14(¹⁴C) as shown here.

The ratio of ³H/¹⁴C is 3. What would the ³H/¹⁴C ratio be after the synthesis of palmitic acid (C₁₆) with the use of the radioactive acetyl CoA?

A tight embrace. Avidin, a glycoprotein found in eggs, has a high affinity for biotin. Avidin can bind biotin and prevent its use by the body. How might a diet rich in raw eggs affect fatty acid synthesis? What will be the effect on fatty acid synthesis of a diet rich in cooked eggs? Explain.

Alpha or omega? Only one acetyl CoA molecule is used directly in fatty acid synthesis. Identify the carbon atoms in palmitic acid that were donated by acetyl CoA.

Now you see it, now you don’t. Although is required for fatty acid synthesis, its carbon atom does not appear in the product. Explain how this omission is possible.

It is all about communication. Why is citrate an appropriate inhibitor of phosphofructokinase?

Tracing carbon atoms. Consider a cell extract that actively synthesizes palmitate. Suppose that 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 carbon atom of 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 are analyzed for radioactivity. Which carbon atom of the palmitate formed by this system is more radioactive—C-1 or C-14?

An unaccepting mutant. The serine residues in acetyl CoA carboxylase that are the target of the AMP-activated protein kinase are mutated to alanine. What is a likely consequence of this mutation?

Sources. For each of the following unsaturated fatty acids, indicate whether the biosynthetic precursor in animals is palmitoleate, oleate, linoleate, or linolenate.

Driven by decarboxylation. What is the role of decarboxylation in fatty acid synthesis? Name another key reaction in a metabolic pathway that employs this mechanistic motif.

Kinase surfeit. Suppose that a promoter mutation leads to the overproduction of protein kinase A in adipose cells. How might fatty acid metabolism be altered by this mutation?

Blocked assets. The presence of a fuel molecule in the cytoplasm does not ensure that the fuel molecule can be effectively used. Give two examples of how impaired transport of metabolites between compartments leads to disease.

Elegant inversion. Peroxisomes have an alternative pathway for oxidizing polyunsaturated fatty acids. They contain a hydratase that converts d-3-hydroxyacyl CoA into trans-Δ²-enoyl CoA. How can this enzyme be used to oxidize CoAs containing a cis double bond at an even-numbered carbon atom (e.g., the cis-Δ¹² double bond of linoleate)?

Arm in arm. Many eukaryotic enzymes, such as fatty acid synthase, are multifunctional proteins with multiple active sites covalently linked. What is the advantage of this arrangement?

Covalent catastrophe. What is a potential disadvantage of having many catalytic sites together on one very long polypeptide chain?

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

Effects of clofibrate. High blood levels of triacylglycerides are associated with heart attacks and strokes. Clofibrate, a drug that increases the activity of peroxisomes, is sometimes used to treat patients with such a condition. What is the biochemical basis for this treatment?

A different kind of enzyme. Figure 22.36 shows the response of acetyl CoA carboxylase to varying amounts of citrate. Explain this effect in light of the allosteric effects that citrate has on the enzyme. Predict the effects of increasing concentrations of palmitoyl CoA.

Variation on a theme. Thiolase is homologous in structure to the condensing enzyme. On the basis of this observation, propose a mechanism for the cleavage of 3-ketoacyl CoA by CoA.

Two plus three to make four. Propose a reaction mechanism for the condensation of an acetyl unit with a malonyl unit to form an acetoacetyl unit in fatty acid synthesis.

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

Fats to glycogen. An animal is fed stearic acid that is radioactively labeled with [¹⁴C]carbon. A liver biopsy reveals the presence of ¹⁴C-labeled glycogen. How is this finding possible in light of the fact that animals cannot convert fats into carbohydrates?

Enzyme deficit. Pyruvate dehydrogenase deficiency, a severe condition with a poor prognosis, results in neurological dysfunction and unremitting lactic acidosis. One treatment is placing the patients on a low carbohydrate/high fat diet.

Right enzymes. Wrong location. Zwellweger syndrome is caused by a defect in enzyme importation into the peroxisomes. What disease of carbohydrate metabolism is caused by inappropriate cellular distribution of enzymes?

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 show data from studies performed to identify the effect of the mutation.

Partners. Colipase binds to lipid particles in the intestine and facilitates the subsequent binding and activation of pancreatic lipase. The lipase then hydrolyzes the lipids so that they can be absorbed by intestinal cells. Experiments were undertaken using site-directed mutagenesis (Section 5.2) to determine which amino acids in the colipase facilitated lipase binding and which activated the lipase. A portion of these experiments is presented below.

Figure A shows the results of two different amino acid substitutions on the ability of colipase to facilitate the binding of lipase to the lipid particles. In both panels, the blue circles show the control (no amino acid changes) data and the red circles the data with the altered amino acid. The first letter represents the normal amino acid, the number its position in the amino acid sequence, and the second letter the replacement amino acid.

Nip it in the bud. Soraphen A is a natural antifungal agent isolated from a myxobacterium. Soraphen A is also a potent inhibitor of acetyl CoA carboxylase, the regulatory enzyme that initiates fatty acid synthesis. As discussed earlier, cancer cells must produce large amount of fatty acids to generate phospholipids for membrane synthesis. Thus, acetyl CoA carboxylase might be a target for anti-cancer drugs. Following are the results of experiments testing this hypothesis on a cancer line.

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Figure A shows the effect of various amounts of soraphen A on fatty acid synthesis as measured by the incorporation of radioactive acetate (¹⁴C) into fatty acids.