Chp 21

Front 1

1. Which of the following is not required in the synthesis of fatty acids? A) Acetyl-CoA B) Biotin C) HCO3– (CO2) D) Malonyl-CoA E) NADH

Back 1

e

Front 2

2. Which of the following is not true of the reaction producing malonyl-CoA during fatty acid synthesis? A) It is stimulated by citrate. B) It requires acyl carrier protein (ACP). C) It requires CO2 (or bicarbonate). D) One mole of ATP is converted to ADP + Pi for each malonyl-CoA synthesized.E) The cofactor is biotin.

Back 2

b

Front 3

3. If malonyl-CoA is synthesized from 14CO2 and unlabeled acetyl-CoA, and the labeled malonate is then used for fatty acid synthesis, the final product (fatty acid) will have radioactive carbon in: A) every C. B) every even-numbered C-atom. C) every odd-numbered C-atom. D) no part of the molecule. E) only the omega-carbon atom (farthest carbon from C-1).

Back 3

d

Front 4

4. Which one of the following statements best applies to synthesis of fatty acids in E. coli extracts?A) Acyl intermediates are thioesters of a low molecular weight protein called acyl carrier protein. B) CO2 or HCO3– is essential. C) Reducing equivalents are provided by NADPH.D) The ultimate source of all the carbon atoms in the fatty acid product is acetyl-CoA. E) All of the above

Back 4

e

Front 5

5. In comparing fatty acid biosynthesis with oxidation of fatty acids, which of the following statements is incorrect? A) A thioester derivative of crotonic acid (trans-2-butenoic acid) is an intermediate in the synthetic path, but not in the degradative path. B) A thioester derivative of D--hydroxybutyrate is an intermediate in the synthetic path, not in the degradative path. C) Fatty acid biosynthesis uses NADPH exclusively, whereas oxidation uses NAD+ exclusively. D) Fatty acid degradation is catalyzed by cytosolic enzymes; fatty acid synthesis by mitochondrial enzymes. E) The condensation of two moles of acetyl-CoA in the presence of a crude extract is more rapid in bicarbonate buffer than in phosphate buffer at the same pH; the cleavage of acetoacetyl-CoA proceeds equally well in either buffer.

Back 5

d

Front 6

6. Which of the following is not true of the fatty acid synthase and the fatty acid -oxidation systems? A) A derivative of the vitamin pantothenic acid is involved. B) Acyl-CoA derivatives are intermediates. C) Double bonds are oxidized or reduced by pyridine nucleotide coenzymes. D) The processes occur in different cellular compartments.E) The processes occur in the mitochondrial matrix.

Back 6

e

Front 7

7. The rate-limiting step in fatty acid synthesis is: A) condensation of acetyl-CoA and malonyl-CoA. B) formation of acetyl-CoA from acetate. C) formation of malonyl-CoA from malonate and coenzyme A. D) the reaction catalyzed by acetyl-CoA carboxylase. E) the reduction of the acetoacetyl group to a -hydroxybutyryl group.

Back 7

d

Front 8

8. Which of the following is not true of the fatty acid elongation system of vertebrate cells? A) It involves the same four-step sequence seen in the fatty acid synthase complex. B) It is located in the smooth endoplasmic reticulum. C) It produces stearoyl-CoA by the extension of palmitoyl-CoA. D) It uses malonyl-CoA as a substrate. E) The immediate precursor of the added carbons is acetyl-CoA.

Back 8

e

Front 9

9. Which of the following is not true about precursors required for fatty acid synthesis in animal cells?A) NADPH is produced in the cytosol by the pentose phosphate pathway.B) NADPH is produced in the nucleus by malic enzyme.C) Acetyl-CoA is transported out of the mitochondrion via the citrate shuttle.D) CoA is not transported across the mitochondrial membrane.E) Malonyl-CoA is formed in the cytosol.

Back 9

b

Front 10

10. Which of these can be synthesized by plants but not by humans? A) Linoleate [18:2(9,12)] B) Palmitate (16:0) C) Phosphatidylcholine D) Pyruvate E) Stearate (18:0)

Back 10

a

Front 11

11. The enzyme system for adding double bonds to saturated fatty acids requires all of the following except: A) a mixed-function oxidase. B) ATP. C) cytochrome b5. D) molecular oxygen (O2). E) NADPH.

Back 11

b

Front 12

12. Which of these statements about eicosanoid synthesis is true? A) An early step in the path to thromboxanes is blocked by ibuprofen. B) Arachidonate is derived mainly by hydrolysis of triacylglycerols.C) Aspirin acts by blocking the synthesis of arachidonate. D) Plants can synthesize leukotrienes, but humans cannot. E) Thromboxanes are produced from arachidonate via the “linear” path.

Back 12

a

Front 13

13. The biosynthesis of triacylglycerols from acetate occurs mainly in: A) animals but not in plants. B) humans after ingestion of excess carbohydrate. C) humans with low carbohydrate intake. D) plants but not in animals. E) None of the above

Back 13

b

Front 14

14. The synthesis of both glycerophospholipids and triacylglycerols involves: A) CDP-choline. B) CDP-diacylglycerol. C) phosphatidate phosphatase. D) phosphatidic acid. E) phosphoethanolamine.

Back 14

d

Front 15

15. Which of these statements about triacylglycerol synthesis is correct? A) Humans can store more energy in glycogen than in triacylglycerols. B) Insulin stimulates conversion of dietary carbohydrate into triacylglycerols. C) It is not a hormone-sensitive process.D) Mammals are unable to convert carbohydrates into triacylglycerols. E) Phosphatidate is not on the pathway of triacylglycerol synthesis.

Back 15

b

Front 16

16. A strategy that is not employed in the synthesis of phospholipids is: A) condensation of CDP-alcohol with diacylglycerol. B) condensation of CDP-diacylglycerol with alcohol. C) condensation of CDP-diacylglycerol with CDP-alcohol. D) exchange of free alcohol with head group alcohol of phospholipid. E) remodeling of head group alcohols by chemical modification

Back 16

b

Front 17

17. All glycerol-containing phospholipids are synthesized from: A) cardiolipinB) ceramide. C) gangliosides. D) mevalonate. E) phosphatidic acid.

Back 17

e

Front 18

19. In the synthesis of phosphatidylcholine from phosphatidylethanolamine, the methyl group donor is: A) a tetrahydrofolate derivative. B) choline. C) methanol. D) S-adenosylmethionine (adoMet). E) serine.

Back 18

d

Front 19

18. In E. coli the synthesis of phosphatidylethanolamine directly involves: A) acyl carrier protein. B) biotin. C) CDP-choline. D) phosphatidylglycerol. E) serine.

Back 19

e

Front 20

20. Palmitoyl-CoA, , is a direct precursor of: A) cholesterol. B) malonyl-CoA. C) mevalonateD) sphingosine. E) squalene.

Back 20

d

Front 21

21. CDP-diglyceride is not involved in the biosynthesis of: A) phosphatidylcholine. B) phosphatidylethanolamineC) phosphatidylglycerol. D) phosphatidylserine. E) sphingomyelin.

Back 21

e

Front 22

22. Which of the following is true of sphingolipid synthesis? A) All of the carbon atoms of palmitate and serine are incorporated into sphingosine. B) CDP-sphingosine is the activated intermediate. C) CO2 is produced during the synthesis of ceramide from palmitate and serine. D) Glucose 6-phosphate is the direct precursor of the glucose in cerebrosides. E) Phosphatidic acid is a key intermediate in the pathway

Back 22

c

Front 23

23. Which of the following is not an intermediate in the synthesis of lanosterol from acetyl-CoA? A) Isopentenyl pyrophosphate B) Malonyl-CoA C) Mevalonate D) Squalene -Hydroxy--methylglutaryl-CoA (HMG-CoA)

Back 23

b

Front 24

24. Cholesterol is synthesized from: A) acetyl-CoA. B) choline. C) lipoic acid. D) malate. E) oxalate.

Back 24

a

Front 25

25. A 30-carbon precursor of the steroid nucleus is: A) farnesyl pyrophosphate. B) geranyl pyrophosphate. C) isopentenyl pyrophosphate. D) lysolecithin. E) squalene.

Back 25

e

Front 26

26. Which of these statements about cholesterol synthesis is true? A) Cholesterol is the only known natural product whose biosynthesis involves isoprene units. B) Only half of the carbon atoms of cholesterol are derived from acetate. C) Squalene synthesis from farnesyl pyrophosphate results in the release of two moles of PPi for each mole of squalene formed. D) The activated intermediates in the pathway are CDP-derivatives. E) The condensation of two five-carbon units to yield geranyl pyrophosphate occurs in a “head-to-head” fashion.

Back 26

c

Front 27

27. Which of the following is derived from a sterol? A) Bile salts B) Gangliosides C) Geraniol D) Phosphatidylglycerol E) Prostaglandins

Back 27

a

Front 28

28. Chylomicrons carry in the . A) triacylglycerols; cell B) triacylglycerols; bloodC) cholesterols; bloodD) fatty acids; blood E) fatty acids; cell

Back 28

b

Front 29

29. Lipoprotein particles in human blood do not contain: A) an apolipoprotein B isoform.B) cholesterol.C) cholesteryl esters.D) lecithin.E) triglycerides.

Back 29

d

Front 30

30. Which of the following contains the highest percentage of cholesteryl esters? A) ChylomicronsB) VLDLC) LDLD) HDLE) None of the above contain any cholesteryl esters.

Back 30

c

Front 31

31. Which of the following is not a step in the uptake of cholesterol from the bloodstream into cells? A) LDL containing ApoB-100 is recognized by the LDL receptor. B) LDL bound to the LDL receptor leads to endocytosis of the complex. C) The cholesteryl esters in the LDL are hydrolyzed to release free cholesterol.D) The internalized receptor is degraded. E) The ApoB-100 protein is degraded.

Back 31

d

Front 32

32. Which of these statements about the regulation of cholesterol synthesis is not true? A) Cholesterol acquired in the diet has essentially no effect on the synthesis of cholesterol in the liver. B) Failure to regulate cholesterol synthesis predisposes humans to atherosclerosis. C) High intracellular cholesterol stimulates formation of cholesteryl esters. D) Insulin stimulates HMG-CoA reductase. E) Some metabolite or derivative of cholesterol inhibits HMG-CoA reductase.

Back 32

a

Front 33

33. Which of the following does not contribute to lowering the risk of atherosclerosis? A) Statin drugsB) HDLC) Reverse cholesterol transportD) ApoA-IE) Foam cells

Back 33

e

Front 34

34. Which of these compounds is not synthesized by a pathway that includes isoprene precursors? A) Natural rubber B) Plastoquinone C) Vitamin A D) Vitamin B12E) Vitamin K

Back 34

e

Front 35

35. If you start with acetyl-CoA labeled with 14C in the methyl-carbon, where does the label end up in malonyl-CoA?

Back 35

Malonyl-CoA would be labeled in C-2 (C-1 is the acyl carbon 834

Front 36

36. If you perform fatty acid biosynthesis with CO2 labeled with 14C, where does the label end up in a fatty acid?

Back 36

There will not be any radioactivity in any fatty acid because the carboxyl group that is added to form malonyl-CoA is lost in the first condensation reaction.

Front 37

37. The reaction sequence that leads to fatty acid synthesis includes (1) condensation, (2) first reduction reaction, (3) dehydration, and (4) second reduction. Show the first reduction reaction, with any required cofactors.

Back 37

: beta-ketoacyl-ACP + NADPH + H+ ===>beta-hydroxyacyl-ACP + NADP+(See Fig. 21-2.)

Front 38

38. Fatty acid synthesis and fatty acid breakdown occur by similar pathways. Describe, very briefly, four ways in which the synthetic and breakdown pathways differ.

Back 38

: Fatty acid synthesis (in any order) (1) employs NADPH as reducing agent; (2) involves an acyl group bound to a protein, ACP; (3) takes place in the cytosol of animals; (4) involves the condensation of malonyl- and acetyl-groups; (5) involves the formation of the D--hydroxyacyl derivative. Fatty acid breakdown (1) employs NAD+ as electron acceptor; (2) involves acyl groups bound to coenzyme A; (3) occurs in the mitochondrial matrix; (4) does not involve malonyl-derivatives; (5) involves the L-stereoisomer of the -hydroxyacyl derivative.

Front 39

39. The synthesis of fatty acids and their breakdown by -oxidation occur by separate pathways. Compare the two paths by filling in the blanks below. (Some blanks may require more than one answer.) Synthesis -oxidation ——————————————————Activating group _______________ ______________Electron carrier coenzyme(s) _______________ ______________Basic units added or removed _______________ ______________Cellular location of process _______________ ______________

Back 39

Ans: Synthesis -oxidation ————————————————————Activating group acyl carrier protein CoA—SHElectron carrier coenzyme(s) NADPH NAD+Basic units added or removed malonyl- and acetyl- acetyl-Cellular location of process cytosol in animals, mitochondrial matrix chloroplast in plants

Front 40

40. Show the structure of each intermediate in the conversion of -hydroxybutyryl-ACP to butyryl-ACP by the fatty acid synthetase complex. Show where cofactors participate. In your first intermediate, circle the carbon atoms that are derived from malonyl-CoA.

Back 40

-hydroxybutyryl-ACP is first dehydrated, yielding trans-2-butenoyl-ACP, which is then reduced to butyryl-ACP, with NADPH as the reducing agent. (See Fig. 21-6.) The carbon atoms coming from malonyl-CoA are those closer to the ACP.

Front 41

41. Describe the mechanism for moving acetyl-CoA produced in the mitochondrial matrix into the cytosol for fatty acid synthesis.

Back 41

Acetyl-CoA in the mitochondrial matrix condenses with oxaloacetate to form citrate in a reaction catalyzed by citrate synthase. Citrate moves out of the matrix via the citrate transporter. Citrate in the cytosol is cleaved by citrate lyase, yielding acetyl-CoA and oxaloacetate. To complete the cycle, oxaloacetate in the cytosol is reduced to malate, which moves into the mitochondrial matrix on the malate--ketoglutarate transporter, and is converted to oxaloacetate in the matrix.

Front 42

42. Explain briefly why we require fats in our diets.

Back 42

Dietary fats provide the linoleate and linolenate that we need (for eicosanoid synthesis) but cannot synthesize.

Front 43

43. Sketch the pathway from arachidonate to thromboxanes and explain how aspirin blocks the synthesis of thromboxanes

Back 43

See Fig. 21-15.) Aspirin blocks the activity of cyclooxygenase (COX).

Front 44

44. Explain the triacylglycerol cycle and how drugs such as rosiglitazone (Avandia) promote this cycle and help lower fatty acid levels in the bloodstream.

Back 44

The triacylgycerol cycle is the constant cycling of fatty acids from adipose tissue to liver and back again. It begins with hydrolysis of fatty acids in adipose tissue followed by transport of the free fatty acids through the bloodstream for re-esterification in the liver. Once in the liver, the process is reversed and the fatty acids end up in adipose tissue again. (See Fig. 21-22.) The constant attaching/detaching of fatty acids requires a relatively high concentration of glycerol-3-phosphate, which is synthesized from pyruvate in a “truncated” gluconeogenic pathway. (See Fig. 21-21.) Drugs such as rosiglitazone promote higher levels of PEP carboxykinase, thus raising the concentration of glycerol-3-phosphate available for re-esterification of free fatty acids in adipose tissue.

Front 45

45. Describe two basic strategies for activating precursors in the biosynthesis of phospholipids.

Back 45

(1) Activate the head group by attachment to CDP, as in CDP-choline, then displace CMP with the hydroxyl group of glycerol in diacylglycerol. (2) Activate diacylglycerol by the attachment of CDP, then displace CMP with the hydroxyl group of the head group.