Chp 18

Front 1

1. Under which circumstances are amino acids not metabolized via oxidative degradation?A) StarvationB) Plants growing in nutrient-rich soilsC) Normal protein turnoverD) A diet rich in proteinsE) Uncontrolled diabetes

Back 1

b 695

Front 2

2. Which of these is not a protease that acts in the small intestine? A) Chymotrypsin B) Elastase C) Enteropeptidase D) Secretin E) Trypsin

Back 2

d 697-698

Front 3

3. In the digestion of protein that occurs in the small intestine, which enzyme is critical in the activation of zymogens? A) Enteropeptidase B) Hexokinase C) Papain D) Pepsin E) Secretin

Back 3

a 698

Front 4

4. Which of the following is a zymogen that can be converted to an endopeptidase that hydrolyzes peptide bonds adjacent to Lys and Arg residues? A) Chymotrypsinogen B) Pepsin C) Pepsinogen D) Trypsin E) Trypsinogen

Back 4

e 698-99

Front 5

5. In amino acid catabolism, the first reaction for many amino acids is a(n): A) decarboxylation requiring thiamine pyrophosphate (TPP). B) hydroxylation requiring NADPH and O2. C) oxidative deamination requiring NAD+.D) reduction requiring pyridoxal phosphate (PLP). E) transamination requiring pyridoxal phosphate (PLP).

Back 5

e 699

Front 6

6. The coenzyme required for all transaminations is derived from: A) niacin. B) pyridoxine (vitamin B6). C) riboflavin. D) thiamin. E) vitamin B12.

Back 6

b 699

Front 7

7. The coenzyme involved in a transaminase reaction is: A) biotin phosphate. B) lipoic acid. C) nicotinamide adenine dinucleotide phosphate (NADP+). D) pyridoxal phosphate (PLP). E) thiamine pyrophosphate (TPP).

Back 7

d 699

Front 8

8. Transamination from alanine to -ketoglutarate requires the coenzyme: A) biotin. B) NADH. C) No coenzyme is involved. D) pyridoxal phosphate (PLP). E) thiamine pyrophosphate (TPP).

Back 8

d 699

Front 9

9. Which of the following reactions involving an amino acid cannot be catalyzed via a PLP-dependent mechanism?A) HydrolysisB) DecarboxylationC) RacemizationD) TransaminationE) Transimination

Back 9

a 700-1

Front 10

10. Which of the following is not true of the reaction catalyzed by glutamate dehydrogenase? A) It is similar to transamination in that it involves the coenzyme pyridoxal phosphate (PLP). B) NH4+ is produced. C) The enzyme can use either NAD+ or NADP+ as a cofactor. D) The enzyme is glutamate-specific, but the reaction is involved in oxidizing other amino acids. E) -Ketoglutarate is produced from an amino acid.

Back 10

a 700-2

Front 11

11. Glutamate is metabolically converted to -ketoglutarate and NH4+ by a process described as: A) deamination. B) hydrolysis. C) oxidative deamination. D) reductive deamination. E) transamination.

Back 11

c 700-2

Front 12

12. The conversion of glutamate to an -ketoacid and NH4+: A) does not require any cofactors. B) is a reductive deamination. C) is accompanied by ATP hydrolysis catalyzed by the same enzyme. D) is catalyzed by glutamate dehydrogenase. E) requires ATP

Back 12

d 700-2

Front 13

13. Urea synthesis in mammals takes place primarily in tissues of the: A) brain. B) kidney. C) liver. D) skeletal muscle. E) small intestine.

Back 13

c 704

Front 14

14. Which substance is not involved in the production of urea from NH4+ via the urea cycle? A) Aspartate B) ATPC) Carbamoyl phosphate D) Malate E) Ornithine

Back 14

d 705

Front 15

15. Which of these directly donates a nitrogen atom for the formation of urea during the urea cycle? A) Adenine B) Aspartate C) Creatine D) Glutamate E) Ornithine

Back 15

b 705

Front 16

16. Conversion of ornithine to citrulline is a step in the synthesis of: A) aspartate. B) carnitine. C) pyruvate. D) tyrosine. E) urea.

Back 16

e 705-6

Front 17

17. In the urea cycle, ornithine transcarbamoylase catalyzes: A) cleavage of urea to ammonia. B) formation of citrulline from ornithine and another reactant. C) formation of ornithine from citrulline and another reactant. D) formation of urea from arginine. E) transamination of arginine.

Back 17

b 705-6

Front 18

18. Which of the following statements is false in reference to the mammalian synthesis of urea? A) Krebs was a major contributor to the elucidation of the pathway involved. B) The amino acid arginine is the immediate precursor to urea. C) The carbon atom of urea is derived from mitochondrial HCO3–.D) The precursor to one of the nitrogens of urea is aspartate. E) The process of urea production is an energy-yielding series of reactions.

Back 18

e 705-6

Front 19

19. Which of the following amino acids are essential for humans? A) Alanine B) Aspartic acid C) AsparagineD) SerineE) Threonine

Back 19

e 709

Front 20

20. If a person’s urine contains unusually high concentrations of urea, which one of the following diets has he or she probably been eating recently? A) High carbohydrate, very low protein B) Very high carbohydrate, no protein, no fatC) Very very high fat, high carbohydrate, no protein D) Very high fat, very low protein E) Very low carbohydrate, very high protein

Back 20

e 709

Front 21

21. Which of these amino acids can be directly converted into a citric acid cycle intermediate by transamination?A) Glutamic acid B) Serine C) Threonine D) TyrosineE) Proline

Back 21

a 707

Front 22

22. Which of these amino acids are both ketogenic and glucogenic?1. Isoleucine2. Valine3. Histidine4. Arginine5. Tyrosine A) 1 and 5 B) 1, 3, and 5 C) 2 and 4 D) 2, 3, and 4 E) 2, 4, and 5

Back 22

a 711

Front 23

23. Tetrahydrofolate (THF) and its derivatives shuttle between different substrates. A) electrons B) H+ C) acyl groups D) one carbon unitsE) NH2 groups

Back 23

d 712

Front 24

24. Which of the following is not a form of the most oxidized state of tetrahydrofolate (THF)?F) N10-formyl THFG) N5N10-methenyl THFH) N5N10-methylene THFI) N5-formyl THFJ) N5-formimino THF2.

Back 24

c 713

Front 25

25. The amino acids serine, alanine, and cysteine can be catabolized to yield: A) fumarate. B) pyruvate. C) succinate. D) -ketoglutarate. E) None of the above

Back 25

b 715-16

Front 26

26. Serine or cysteine may enter the citric acid cycle as acetyl-CoA after conversion to: A) oxaloacetate. B) propionate. C) pyruvate. D) succinate. E) succinyl-CoA.

Back 26

c 715-16

Front 27

27. The human genetic disease phenylketonuria (PKU) can result from: A) deficiency of protein in the diet. B) inability to catabolize ketone bodies. C) inability to convert phenylalanine to tyrosine. D) inability to synthesize phenylalanine. E) production of enzymes containing no phenylalanine.

Back 27

c 717-720

Front 28

28. In the human genetic disease maple syrup urine disease, the metabolic defect involves: A) a deficiency of the vitamin niacin. B) oxidative decarboxylation. C) synthesis of branched chain amino acids. D) transamination of an amino acid. E) uptake of branched chain amino acids into liver.

Back 28

b 717, 723

Front 29

29. Which of these amino acids are converted to -ketoglutarate?1. Glycine2. Glutamate3. Histidine4. Arginine5. ProlineA) 1, 3, and 5 B) 2, 3, and 4 C) 2, 3, and 5 D) 2, 3, 4, and 5 E) 3, 4, and 5

Back 29

d 721

Front 30

30. Which of these amino acids are converted to succinyl CoA?1. Isoleucine2. Valine3. Methionine4. Arginine5. ThreonineA) 2 and 4 B) 2, 3, and 4 C) 2, 4, and 5 D) 1 and 5E) 1, 3, and 5

Back 30

e 722

Front 31

31. Which of these amino acids are converted to oxaloacetate?1. Asparagine2. Glutamine3. Serine4. Arginine5. AspartateA) 2 and 4 B) 2, 3, and 4 C) 2, 4, and 5 D) 1 and 5E) 1, 3, and 5

Back 31

d 724

Front 32

32. Describe (briefly) the role of (a) gastrin, (b) pepsinogen, (c) cholecystokinin, and (d) enteropeptidase in protein digestion.

Back 32

The hormone gastrin stimulates secretion of HCl and pepsinogen into the stomach; (b) pepsinogen, after its conversion to pepsin, begins protein degradation in the stomach; (c) the hormone cholecystokinin stimulates the secretion of the pancreatic zymogens chymotrypsinogen, trypsinogen, and procarboxypeptidase into the small intestine; (d) enteropeptidase is a proteolytic enzyme that activates trypsinogen in the small intestine. Trypsin in turn activates chymotripsinogen, procarboxypeptidases, proelastase, and trypsinogen itself.697-8

Front 33

33. In the treatment of diabetes, insulin is given intravenously. Why can’t this hormone, a small protein, be taken orally?

Back 33

: First, the biological activity of insulin would be destroyed by the low pH of the gastric juice and the proteases that act in the small intestine. Furthermore, even if insulin escaped degradation in the intestine, it would not enter the bloodstream from the intestine; the transport systems in the cells that line the intestinal lumen transport free amino acids, not intact proteins.697-98

Front 34

34. The bacterium responsible for gastric ulcers, Helicobacter pylori, survives the acidic pH of the stomach surprisingly well. It does so in part by synthesizing and excreting large amounts of the enzyme urease, which hydrolyzes urea to bicarbonate and ammonia. Explain how these reaction products lead to a less acidic environment for H. pylori.

Back 34

: Bicarbonate is a good buffer. Additionally, any excess bicarbonate that is converted to carbon dioxide generates an additional hydroxide ion that can then neutralize a proton from the stomach. The other reaction product, ammonia, also readily neutralizes a proton, forming NH4+. 697-08

Front 35

35. Define zymogen and describe the role of one zymogen in protein digestion.

Back 35

A zymogen is an inactive form of an enzyme that can be activated by proteolytic cleavage. The pancreatic enzymes pepsinogen, chymotrypsinogen, trypsinogen, and procarboxypeptidases A and B are all inactive forms of proteases, which are activated by proteolytic cleavage after their release into the small intestine. 697

Front 36

36. Transamination reactions are catalyzed by a family of enzymes, all of which require __________ as a coenzyme. In the first step of a transamination, the coenzyme in the aldehyde form condenses with the _________ group of an amino acid to form a(n) _________.

Back 36

pyridoxal phosphate (PLP); -amino; Schiff base (or imine or aldimine) 699

Front 37

37. Draw the structures of reactants and products in the transamination in which glutamate and pyruvate are the starting materials. What cofactor is required for this reaction?

Back 37

The correct answer is the reverse of the reaction shown in Fig. 18-4, with R = CH3. Pyridoxal phosphate (PLP) is the cofactor. 699

Front 38

38. Give the name and draw the structure of the -keto acid resulting when the following amino acids undergo transamination with -ketoglutarate: (a) glutamate; (b) aspartate; (b) alanine.

Back 38

Ans: (a) -ketoglutarate; (b) oxaloacetate; (b) pyruvate; see Fig. 18-4 pg699

Front 39

39. Describe, by showing the chemical intermediates, the role of pyridoxal phosphate (PLP) in the transamination of an amino acid.

Back 39

See the top line of Fig. 18-6.

Front 40

40. Describe the roles of glutamine synthetase and glutaminase in the metabolism of amino groups in mammals.

Back 40

: In tissues that are metabolizing the carbon skeletons of amino acids, the amino groups are transferred by transamination to glutamate, then released as ammonia. Ammonia, which is toxic, is then combined with glutamate to form glutamine; the reaction is catalyzed by glutamine synthetase and requires ATP. Glutamine is moved from the extrahepatic tissues to the liver and kidneys, where the amino group is released from glutamine by glutaminase; the products are glutamate and ammonia. The ammonia delivered in this way to the liver is converted to urea, then excreted. p701-03

Front 41

41. Show the reaction in which ammonia is formed from glutamate; include any required cofactors and/or intermediates.

Back 41

This is the reaction catalyzed by glutamate dehydrogenase; see Fig. 18-7 pg 702

Front 42

42. Describe the reactions and the role of the glucose-alanine cycle.

Back 42

Toxic ammonia formed by amino acid catabolism in muscle is transported to the liver as alanine, which is nontoxic. Alanine is formed in muscle by transamination of pyruvate (formed by glycolysis); glutamate formed by glutamate dehydrogenase is the amino donor. In the liver, alanine is reconverted to pyruvate by transamination. Its amino group is eventually converted to urea, and the pyruvate is converted to glucose by gluconeogenesis in the liver, then exported to muscle. pg704

Front 43

43. Why does a mammal go to all of the trouble of making urea from ammonia rather than simply excreting ammonia as many bacteria do?

Back 43

When bacteria release ammonia into the surrounding medium, it is diluted to nontoxic levels. The ammonia produced by amino acid catabolism in mammals cannot be sufficiently diluted in the tissues and the blood to avoid accumulating at toxic levels. Urea is much less toxic than ammonia.pg704

Front 44

44. Describe the three different forms of nitrogen by which different organisms dispose of excess nitrogen obtained in the diet. Give examples of organisms that produce these different forms.

Back 44

1) Ammonotelic: release into the surrounding medium as NH4+ (bacteria and many marine organisms); (2) Uricotelic: production of uric acid (birds and reptiles); (3) Ureotelic: production and excretion of urea (land-dwelling animals).704

Front 45

45. Amino acid catabolism involves the breakdown of 20 amino acids all of which contain nitrogen but have different carbon skeletons. What overall strategy is used to deal with this problem? Illustrate the strategy with two examples.

Back 45

: Nitrogen is removed by transamination to glutamate. This converts the amino acid to an -keto acid that either is an intermediate in carbohydrate catabolism or is converted to one. (See Fig. 18-2) Examples are shown in Fig. 18-10.

pg 697, 706

Front 46

46. During starvation, more urea production occurs. Explain this observation.

Back 46

During starvation, cellular proteins are degraded and their carbon skeletons are oxidized for energy. The first step in amino acid catabolism is removal of the amino groups, which are ultimately excreted as urea.. 708

Front 47

47. Describe (a) the fundamental nutritional problem faced by individuals with genetic defects in enzymes involved in urea formation and (b) two approaches to treatment of these diseases.

Back 47

(a) A defect in urea synthesis can result in the formation of toxic blood levels of ammonia from the breakdown of ingested proteins. Thus, it is desirable to limit the intake of amino acids. However, some amino acids are essential for humans (i.e., not biosynthesized) and hence must be ingested in adequate amounts. (b) One approach is to administer compounds that deplete the supply of glycine and glutamine. The replenishment of these amino acids removes ammonia from the blood. Another approach is to administer compounds that allow the liver to bypass the enzyme that is defective in the individual. 709-710

Front 48

48. Explain why one might provide high concentrations of the amino acid Arg to patients who have a deficiency in one of the first three enzymes of the urea cycle.

Back 48

The Arg is converted efficiently to urea and ornithine since the last enzyme of the urea cycle is still functioning normally. Thus, one produces higher than normal concentrations of ornithine, which is required for the rest of the cycle to work. That is, you increase the flux through the pathway by providing higher concentrations of the intermediates. 709-10

Front 49

49. Name four amino acids that can be converted directly (in one step) into pyruvate or a citric acid cycle intermediate, and name the intermediate formed from each.

Back 49

: (1) aspartate; oxaloacetate; (2) glutamate; -ketoglutarate; (3) alanine; pyruvate; (4) serine; pyruvate. (Order is not important.) 710-11

Front 50

50. Name one amino acid whose oxidation proceeds via the intermediate shown: (a) pyruvate; (b) oxaloacetate; (c) -ketoglutarate; (d) succinyl-CoA; (e) fumarate.

Back 50

Possible answers are: (a) alanine, tryptophan, glycine, serine, cysteine; (b) aspartate, asparagine; (c) glutamate, glutamine, arginine, histidine, proline; (d) isoleucine, threonine, methionine, valine; (e) phenylalanine, tyrosine. 710-11

Front 51

51. Degradation of amino acids yields compounds that are common intermediates in the major metabolic pathways. Explain the distinction between glucogenic and ketogenic amino acids in terms of their metabolic fates.

Back 51

The glucogenic amino acids are those that are catabolized to intermediates that can serve as substrates for gluconeogenesis: pyruvate and any of the four- or five-carbon intermediates of the citric acid cycle. Ketogenic amino acids are catabolized to yield acetyl-CoA or acetoacetyl-CoA, the precursors for ketone body formation 710-11

Front 52

52. There are bacteria for which alanine can serve as the chief energy source; they oxidize the carbon skeleton of this amino acid, thereby generating ATP. Describe the first step in alanine degradation; show any cofactors that participate.

Back 52

The first step is removal of the amino group by transamination, in which pyridoxal phosphate (PLP) serves as an essential cofactor and -ketoglutarate is the usual amino group acceptor: PLP Alanine + -ketoglutarate pyruvate + glutamate p 715

Front 53

53. If you received a laboratory report showing the presence of a high concentration of phenylalanine and its metabolites in the urine of a patient, what disease would you suspect? What defect(s) in metabolism account(s) for the accumulation of phenylalanine in such patients?

Back 53

Phenylketonuria, the disease that results from a defect in either phenylalanine hydroxylase or the enzyme that catalyzes regeneration of tetrahydrobiopterin 718-720

Front 54

54. Suppose you are responsible for formulating the diet for a 4-year-old boy with phenylketonuria. How do you decide what kind and amount of protein to include in the diet?

Back 54

A growing child needs a certain amount of phenylalanine and tyrosine for the synthesis of new proteins. Because an excess of phenylalanine and tyrosine is toxic in phenylketonurics, the diet should include just enough of these amino acids in protein to supply these needs, but not enough so that phenylketones begin to accumulate in the blood and urine. If the defect causing phenylketonuria lies in the enzyme that regenerates tetrahydrobiopterin, l-3,4-dihydroxyphenylalanine and 5-hydroxytryptophan must also be supplied in the diet. Adding tetrahydrobiopterin to the diet will not help because the compound is unstable and cannot cross the blood-brain barrier.718-720

Front 55

55. Diagram the degradative pathway from proline to an intermediate of either glycolysis or the citric acid cycle. Show structures of intermediates and indicate where cofactors are involved.

Back 55

The shortest pathway is from proline to 1-pyrroline-5-carboxylate, glutamate semialdehyde, glutamate, and -ketoglutarate. See Fig. 18-26. pg 721-22