Problem 1
Using your knowledge of fatty acid biosynthesis, provide an explanation for the two experimental observations. a. A biochemist adds uniformly labeled \(\left[{ }^{14} \mathrm{C}\right]\) acetyl-CoA to a soluble liver fraction, which yields palmitate uniformly labeled with \({ }^{14} \mathrm{C}\). b. In a second experiment, the biochemist adds a trace of uniformly labeled \(\left.{ }^{[14} \mathrm{C}\right]\) acetyl-CoA in the presence of an excess of unlabeled malonyl-CoA to a soluble liver fraction, which yields palmitate labeled with \({ }^{14} \mathrm{C}\) only in C-15 and C-16.
Problem 2
After a person has ingested large amounts of sucrose, the body transforms the glucose and fructose that exceed caloric requirements to fatty acids for triacylglycerol synthesis. This fatty acid synthesis consumes acetyl-CoA, ATP, and NADPH. How do cells produce acetyl-CoA, ATP, and NADPH from glucose?
Problem 4
A researcher has prepared a solution that contains all the enzymes and cofactors necessary for fatty acid biosynthesis from added acetyl-CoA and malonyl-CoA. a. She then adds \(\left[2-{ }^{2} \mathrm{H}\right]\) acetyl-CoA (labeled with deuterium, the heavy isotope of hydrogen) and an excess of unlabeled malonyl- CoA as substrates. How many deuterium atoms incorporate into every molecule of palmitate? What are their locations? Explain. b. In a separate experiment, the researcher adds unlabeled acetyl-CoA and \(\left[2-{ }^{2} \mathrm{H}\right]\) malonyl-CoA as substrates. How many deuterium atoms incorporate into every molecule of palmitate? What are their locations? Explain.
Problem 12
A young rat maintained on a diet deficient in methionine fails to thrive unless choline is included in the diet. Explain.
Problem 13
The formation of a thioester of acetoacetate is catalyzed by fatty acid synthase during fatty acid synthesis, and by acetyl-CoA acetyltransferase in the first step of cholesterol biosynthesis. Both are Claisen condensations. However, in fatty acid synthesis, malonyl-CoA forms in an earlier step so that decarboxylation facilitates the condensation. In the cholesterol biosynthesis pathway, the condensation occurs between two acetyl-CoA molecules, and no decarboxylation occurs to facilitate the reaction. Suggest a reason why the thermodynamic augmentation of decarboxylation is needed in fatty acid synthesis, but not in the first steps of cholesterol biosynthesis.
Problem 15
In the biosynthesis of complex lipids, components are assembled by transfer of the appropriate group from an activated donor. For example, the activated donor of acetyl groups is acetyl-CoA. For each of the following groups, give the form of the activated donor: a. phosphate; b. D-glucosyl; c. phosphoethanolamine; d. D-galactosyl; e. fatty acyl; f. methyl; g. the two-carbon group in fatty acid biosynthesis; h. \(\Delta^{3}\)-isopentenyl.
Problem 16
When young rats are placed on a completely fat-free diet, they grow poorly, develop a scaly dermatitis, lose hair, and soon die. These symptoms can be prevented if linoleate or plant material is included in the diet. What makes linoleate an essential fatty acid? Why can plant material be substituted?
Problem 18
Patients treated with a statin drug generally exhibit a dramatic lowering of serum cholesterol. However, the amount of the enzyme HMG-CoA reductase present in cells can increase substantially. Suggest a simple explanation for this effect.
