1.  Making fat. Write a balanced equation for the synthesis of a triacylglycerol, starting from glycerol and fatty acids. ✓ 5

2.  Making a phospholipid. Write a balanced equation for the synthesis of phosphatidylserine by the de novo pathway, starting from serine, glycerol, and fatty acids. ✓ 5

3.  Needed supplies. How is the glycerol 3-phosphate required for phosphatidate synthesis generated? ✓ 5

4.  ATP needs. How many high-phosphoryl-transfer-potential molecules are required to synthesize phosphatidylethanolamine from ethanolamine and diacylglycerol? Assume that the ethanolamine is the activated component. ✓ 5

5.  Identifying differences. Differentiate among sphingomyelin, a cerebroside, and a ganglioside. ✓ 5

6.  Like Wilbur and Orville. Match each term with its description. ✓ 5

7.  Activated donors. What is the activated reactant in each of the following biosyntheses? ✓ 5

(a) Phosphatidylinositol from inositol

(b) Phosphatidylethanolamine from ethanolamine

(c) Ceramide from sphingosine

(d) Sphingomyelin from ceramide

(e) Cerebroside from ceramide

(f) Farnesyl pyrophosphate from geranyl pyrophosphate

8.  Let’s count the ways. There may be 50 ways to leave your lover, but, in principle, there are only two ways to make a glycerol-based phospholipid. Describe the two pathways. ✓ 5

9.  The Decider. What enzyme plays the key role in the regulation of lipid synthesis, and how is the regulation manifested? ✓ 5

10.  No DAG, no TAG. What would be the effect of a mutation that decreased the activity of phosphatidic acid phosphatase? ✓ 5

11.  Turn 10 around. What would be the effect of a mutation that increased the activity of phosphatidic acid phosphatase? ✓ 5

12.  The Law of Three Stages. What are the three stages required for the synthesis of cholesterol? ✓ 6

13.  Telltale labels. What is the distribution of isotopic labeling in cholesterol synthesized from each of the following precursors? ✓ 6

(a) Mevalonate labeled with ¹⁴C in its carboxyl carbon atom

(b) Malonyl CoA labeled with ¹⁴C in its carboxyl carbon atom

14.  Too much, too soon. What is familial hypercholesterolemia, and what are its causes? ✓ 6

15.  Many regulations to follow. Outline the mechanisms of the regulation of cholesterol biosynthesis. ✓ 6

16.  A good thing. What are statins? What is their pharmacological function? ✓ 6

17.  Too much of a good thing. Would the development of a “super statin” that inhibited all HMG-CoA reductase activity be a useful drug? Explain. ✓ 6

18.  Controlling agents. What are the five major classes of steroid hormones?

19.  Developmental catastrophe. Propecia (finasteride) is a synthetic steroid that functions as a competitive and specific inhibitor of 5 α-reductase, the enzyme responsible for the synthesis of dihydrotestosterone from testosterone.



Propecia is now widely used to retard the development of male pattern baldness. Pregnant women are advised to avoid even handling this drug. Why is it vitally important that pregnant women avoid contact with Propecia?

20.  Breakfast conversation. You and a friend are eating breakfast together. While eating, your friend is reading the back of her cereal box and comes across the following statement: “Cholesterol plays beneficial roles in your body, making cells, hormones, and tissues.” Knowing that you are taking biochemistry, she asks if the statement makes sense. What do you reply? ✓ 6

21.  Let the sun shine in. At a biochemical level, vitamin D functions like a steroid hormone. Therefore, it is sometimes referred to as an honorary steroid. Why is vitamin D not an actual steroid?

22.  A means of entry. Describe the process of receptor-mediated endocytosis by using LDL as an example. ✓ 6

23.  Personalized medicine. The cytochrome P450 system metabolizes many medicinally useful drugs. Although all human beings have the same number of P450 genes, individual polymorphisms exist that alter the specificity and efficiency of the proteins encoded by the genes. How could knowledge of individual polymorphisms be useful clinically?

24.  Honeybee crisis. In 2006, honeybee colonies suddenly and unexplainably died off throughout the United States. The die-off was economically significant because one-third of the human diet comes from insect-pollinated plants and honeybees are responsible for 80% of the pollination. In October of 2006, the sequence of the honeybee genome was reported. Interestingly, the genome was found to contain far fewer cytochrome P450 genes than do the genomes of other insects. Suggest how the die-off and the paucity of P450 genes may be related.

25.  Hold on tight or you might be thrown to the cytoplasm. Many proteins are modified by the covalent attachment of a farnesyl (C₁₅) or a geranylgeranyl (C₂₀) unit to the carboxyl-terminal cysteine residue of the protein. Suggest why this modification might be the case.

26.  Similarities. Compare the role of CTP in phosphoglyceride synthesis with the role of UTP in glycogen synthesis.

27.  ATP requirements. Explain how cholesterol synthesis depends on the activity of ATP-citrate lyase.

28.  Fork in the road. 3-Hydroxy-3-methylglutaryl CoA is on the pathway for cholesterol biosynthesis. It is also a component of another pathway. Name the pathway. What determines which pathway 3-hydroxy-3-methylglutaryl CoA follows? ✓ 6

29.  Drug resistance. Dichlorodiphenyltrichloroethane (DDT) is a potent insecticide rarely used today because of its effects on other forms of life. In insects, DDT disrupts sodium channel function and leads to eventual death. Mosquitos have developed resistance to DDT and other insecticides that function in a similar fashion. Suggest two means by which DDT resistance might develop.

30.  Cholesterol feeding. Mice were divided into four groups, two of which were fed a normal diet and two of which were fed a cholesterol-rich diet. HMG-CoA reductase mRNA and protein from their livers were then isolated and quantified. Graph A shows the results of the mRNA isolation.



(a) What is the effect of cholesterol feeding on the amount of HMG-CoA reductase mRNA?

(b) What is the purpose of also isolating the mRNA for the protein actin, which is not under the control of the sterol response element?

HMG-CoA reductase protein was isolated by precipitation with a monoclonal antibody to HMGCoA reductase. The amount of HMG-CoA protein in each group is shown in graph B.



(c) What is the effect of the cholesterol diet on the amount of HMG-CoA reductase protein?

(d) Why is this result surprising in light of the results in graph A?

(e) Suggest possible explanations for the results shown in graph B. ✓ 6

31.  Familial hypercholesterolemia. Several classes of LDL-receptor mutations have been identified as causes of familial hypercholesterolemia. Suppose that you have been given cells from patients with different mutations, an antibody specific for the LDL receptor that can be seen with an electron microscope, and access to an electron microscope. What differences in antibody distribution might you expect to find in the cells from different patients? ✓ 6

32.  Inspiration for drug design. Some actions of androgens are mediated by dihydrotestosterone, which is formed by the reduction of testosterone. This finishing touch is catalyzed by an NADPH-dependent 5 α-reductase. Chromosomal XY males with a genetic deficiency of this reductase are born with a male internal urogenital tract but predominantly female external genitalia. These people are usually reared as girls. At puberty, they masculinize because the testosterone level rises. The testes of these reductase-deficient men are normal, whereas their prostate glands remain small. How might this information be used to design a drug to treat benign prostatic hypertrophy, a common consequence of the normal aging process in men? A majority of men older than age 55 have some degree of prostatic enlargement, which often leads to urinary obstruction.

33.  Life-style consequences. The cytochrome P450 system is a ubiquitous superfamily of monooxygenases that is present in plants, animals, and prokaryotes. The human genome encodes more than 50 members of the family, whereas the genome of the plant Arabidopsis encodes more than 250 members. These enzymes are responsible for the synthesis of toxins in plants. Why does the fact that plants have more of these enzymes make sense?

34.  Removal of odorants. Many odorant molecules are highly hydrophobic and concentrate within the olfactory epithelium. They would give a persistent signal independent of their concentration in the environment if they were not rapidly modified. Propose a mechanism for converting hydrophobic odorants into water-soluble derivatives that can be rapidly eliminated.