Echevarria Jonille S

BSP 2

1. Reactions that require ATP: phosphorylation of glucose to give glucose-6-phosphate and

phosphorylation of fructose6-phosphate to give fructose-1,6-bisphosphate. Reactions that
produce ATP: transfer of phosphate group from 1,3- bisphosphoglycerate to ADP and transfer
of phosphate group from phosphoenolpyruvate to ADP. Enzymes that catalyze reactions
requiring ATP: hexokinase, glucokinase, and phosphofructokinase. Enzymes that catalyze
reactions producing ATP: phosphoglycerate kinase and pyruvate kinase.

2. Reactions that require NADH: reduction of pyruvate to lactate and reduction of acetaldehyde to
ethanol. Reactions that require NAD1: oxidation of glyceraldehyde-3-phosphate to give 1,3-
diphosphoglycerate. Enzymes that catalyze reactions requiring NADH: lactate dehydrogenase
and alcohol dehydrogenase. Enzymes that catalyze reactions requiring NAD1: glyceraldehyde-3-
phosphate dehydrogenase.

3. Pyruvate can be converted to lactate, ethanol, or acetyl-CoA

4. Aldolase catalyzes the reverse aldol condensation of fructose-1,6-bisphosphate to

glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

5. Isozymes are oligomeric enzymes that have slightly different amino acid compositions in
different organs. Lactate dehydrogenase is an example, as is phosphofructokinase.

6. Isozymes allow for subtle control of the enzyme to respond to different cellular needs. For
example, in the liver, lactate dehydrogenase is most often used to convert lactate to pyruvate,
but the reaction is often reversed in the muscle. Having a different isozyme in the muscle and
liver allows for those reactions to be optimized.

7. Fructose-1,6-bisphosphate can only undergo the reactions of glycolysis. The components of the
pathway up to this point can have other metabolic fates.

8. Add the ΔG°’ mol-1 values for the reactions from glucose to glyceraldehyde-3-phosphate. The
result is 2.5 kJ mol-1 5 0.6 kcal mol-1.

9. The two enzymes can have different tissue locations and kinetic parameters. The glucokinase
has a higher KM for glucose than hexokinase. Thus, under conditions of low glucose, the liver
does not convert glucose to glucose-6-phosphate, using the substrate that is needed elsewhere.
When the glucose concentration is much higher, however, glucokinase helps phosphorylate
glucose so that it can be stored as glycogen.
10. Individuals who lack the gene that directs the synthesis of the M form of the enzyme can carry
on glycolysis in their livers but experience muscle weakness because they lack the enzyme in
muscle.

11. The hexokinase molecule changes shape drastically on binding to substrate, consistent with the
induced-t theory of an enzyme adapting itself to its substrate.
12. ATP inhibits phosphofructokinase, consistent with the fact that ATP is produced by later
reactions of glycolysis.

13. From the point at which aldolase splits fructose-1,6-bisphosphate into dihydroxyacetone
phosphate and glyceraldehyde3-phosphate; all reactions of the pathway are doubled.

14. NADH-linked dehydrogenases: Glyceraldehyde-3-phosphate dehydrogenase, lactate

dehydrogenase, and alcohol dehydrogenase.

15. The free energy of hydrolysis of a substrate is the energetic driving force in substrate-level
phosphorylation. An example is the conversion of glyceraldehyde-3-phosphate to 1,3-
bisphosphoglycerate.

16. The control points in glycolysis are the reactions catalyzed by hexokinase, phosphofructokinase,
and pyruvate kinase.

17. Hexokinase is inhibited by glucose-6-phosphate. Phosphofructokinase is inhibited by ATP and

citrate. Pyruvate kinase is inhibited by ATP, acetyl-CoA, and alanine. Phosphofructokinase is
stimulated by AMP and fructose-2,6-bisphosphate. Pyruvate kinase is stimulated by AMP and
fructose-1,6-bisphosphate.

18. The part of the active site that binds to NADH would be the part that is most conserved, since
many dehydrogenases use that coenzyme.

19. (a) Using a high-energy phosphate to phosphorylate a substrate.

(b) Changing the form of a molecule without changing its empirical formula
(c) Performing an aldol cleavage of a sugar to yield two smaller sugars or sugar derivatives.
(d) Changing the oxidation state of a substrate by removing hydrogens while simultaneously
changing the oxidation state of a coenzyme

20. An isomerase is a general term for an enzyme that changes the form of a substrate without
changing its empirical formula. A mutase is an enzyme of the isomerase class that moves a
functional group, such as a phosphate, to a new location in a substrate molecule.

21. The reaction of 2-phosphoglycerate to phosphoenolpyruvate is a dehydration rather than a

redox reaction.
22. Carbon-1 of glyceraldehyde is the aldehyde group. It changes oxidation state to a carboxylic
acid, which is phosphorylated simultaneously.

23. ATP is an inhibitor of several steps of glycolysis as well as other catabolic pathways. The
purpose of catabolic pathways is to produce energy, and high levels of ATP mean the cell
already has sufficient energy. Glucose-6-phosphate inhibits hexokinase and is an example of
product inhibition. If the glucose-6-phosphate level is high, it may indicate that sufficient
glucose is available from glycogen breakdown or that the subsequent enzymatic steps of
glycolysis are going slowly. Either way, there is no reason to produce more glucose6-phosphate.
Phosphofructokinase is inhibited by a special effector molecule, fructose-2,6-bisphosphate,
whose levels are controlled by hormones. It is also inhibited by citrate, which indicates that
there is sufficient energy from the citric acid cycle, probably from fat and amino acid
degradation. Pyruvate kinase is also inhibited by acetyl-CoA, the presence of which indicates
that fatty acids are being used to generate energy for the citric acid cycle. The main function of
glycolysis is to feed carbon units to the citric acid cycle. When these carbon skeletons can come
from other sources, glycolysis is inhibited to spare glucose for other purposes.

24. There would be 15 possible isozymes of LDH, combining three different subunits into
combinations of four. Besides the five isozymes containing only M and H, there would also be
C4, CH3, C2H2, C3H, CH2M, C2HM, C3M, CHM2, C2M2, and CM3.

25. Glutamic acid has an acidic side chain with a pK a of 4.25. Therefore, it would be negatively
charged at pH 8.6, and the H subunit would move more toward the anode (+) than the M
subunit. Thus, LDH 1, which is H4, would move the farthest. LDH 5, which is M 4, would move the
least, with the other isozymes migrating between those two extremes proportional to their H
content.

26. With few exceptions, a biochemical reaction typically results in only one chemical modification
of the substrate. Accordingly, several to many steps are needed to reach the ultimate goal.

27. The enzyme contains a phosphate group on a suitable amino acid, such as serine, threonine, or
histidine. The substrate donates its phosphate group from the C-3 position to another amino
acid on the enzyme, subsequently receiving the one that started out on the enzyme. Thus, the
32
P that was on the substrate is transferred to the enzyme, while an unlabeled phosphorus is
put on the C-2 position.

28. The bubbles in beer are CO2, produced by alcoholic fermentation. Tired and aching muscles are
caused in part by a buildup of lactic acid, a product of anaerobic glycolysis.

29. The problem with lactic acid is that it is an acid. The H + produced from lactic acid formation
causes the burning muscle sensation. Sodium lactate is the conjugate weak base of lactic acid. It
is reconverted to glucose by gluconeogenesis in the liver. Giving sodium lactate intravenously is
a good way to supply an indirect source of blood glucose.
30. The purpose of the step that produces lactic acid is to re duce pyruvate so that NADH can be
oxidized to NAD+, which is needed for the step catalyzed by glyceraldehyde3-phosphate
dehydrogenase.

31.

32. . Thiamine pyrophosphate is a coenzyme in the transfer of two-carbon units. It is required for
catalysis by pyruvate decarboxylase in alcoholic fermentation.

33. The important part of TPP is the five-membered ring, in which a carbon is found between
nitrogen and sulfur. This carbon forms a carbanion that is extremely reactive, making it able to
perform a nucleophilic attack on carbonyl groups, leading to decarboxylation of several
compounds in different pathways.

34. Thiamine pyrophosphate is a coenzyme required in the reaction catalyzed by pyruvate

carboxylase. Because this reaction is a part of the metabolism of ethanol, less will be available
to serve as a coenzyme in the reactions of other enzymes that require it.

35. Animals that have been run to death have accumulated large amounts of lactic acid in their
muscle tissue, accounting for the sour taste of the meat.

36. Conversion of glucose to lactate rather than pyruvate recycles NADH.

37. This is possible, and it is done. These poisons also affect other tissues, including skin, hair, cells
of the intestinal lining, and especially the immune system and red blood cells. People on
chemotherapy are usually more susceptible to infectious diseases than healthy people and are
often somewhat anemic.

38. 38. The Warburg effect is the high level of glycolysis in cancer cells, giving rise to pyruvate,
followed by lactic acid fermentation. This effect is observed even at high levels of oxygen,
where further oxidation to carbon dioxide and water is expected. This is one of the many
aspects of glycolysis, which is the main subject of this chapter.
39. Research is in progress to modify pyruvate kinase isozymes typical of cancer cells to resemble
those of normal cells. The goal is to redirect metabolism to that of normal cells, rather than
cancer cells.

40. The energy released by all the reactions of glycolysis is 184.5 kJ mol -1 glucose-1. The energy
released by glycolysis drives the phosphorylation of two ADP to ATP for each molecule of
glucose, trapping 61.0 kJ mol-1 glucose-1 The estimate of 33% efficiency comes from the
calculation (61.0/184.5) x 100 = 33%.

41. . There is a net gain of two ATP molecules per glucose molecule consumed in glycolysis.

42. The gross yield is four ATP molecules per glucose molecule, but the reactions of glycolysis
require two ATP per glucose.

43. The reactions catalyzed by hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate

dehydrogenase, phosphoglycerokinase, and pyruvate kinase.

44. The steps catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase.

45. Phosphoenolpyruvate pyruvate + P i

ΔG°’ = -61.9 kJ mol-1 = -14.8 kcal mol-1
ADP + Pi ATP
ΔG°’ = 30.5 kJ mol-1 = 7.3 kcal mol-1
Phosphoenolpyruvate + ADP Pyruvate + ATP
ΔG°’ = =31.4 kJ mol = -7.5 kcal mol-1
-1

46. The net yield of ATP from glycolysis is the same, two ATP, when either of the three substrates is
used. The energetics of the conversion of hexoses to pyruvate are the same, regardless of
hexose type.

47. Starting with glucose-1-phosphate, the net yield is three ATP, because one of the priming
reactions is no longer used. Thus, glycogen is a more efficient fuel for glycolysis than free
glucose.

48. Phosphoenolpyruvate + ADP Pyruvate + ATP

49. No, the reaction shown in Question 48 does not occur in nature. We can assume that no
enzyme evolved that could catalyze it. Nature is not 100% efficient.
50. A positive ΔG°’ does not necessarily mean that the reaction has a positive ΔG. Substrate
concentrations can make a negative ΔG out of a positive ΔG°’.
51. The entire pathway can be looked at as a large coupled reaction. Thus, if the overall pathway
has a negative ΔG, an individual step may be able to have a positive ΔG, and the pathway can
still continue.

52. The formation of fructose-1,6-bisphosphate is the committed step in the glycolytic pathway. It is
also one of the energy-requiring steps of the pathway. Control is exercised here.

53. Glucose-6-phosphate inhibits hexokinase, the enzyme responsible for its own formation.
Because G-6-P is used up by additional reactions of glycolysis, the inhibition is relieved.

54. Hormones exercise another level of control over metabolism, beyond that of allosteric and
feedback control. Glycolysis can certainly be affected in this manner. The effect of insulin on
carbohydrate metabolism is well known.

55. Exerting control at the end of a pathway is a good example of feedback control, so it is
reasonable to expect it.