Chapter 17: Gluconeogenesis

Question 1

Biotin provides __________ for the pyruvate carboxylase reaction.

Answer 1

1. carboxylation of pyruvate
2. a long flexible arm for active site location of substrate
3. group transfer from one site of the enzyme to another

Question 2

The phosphoryl donor in the formation of phosphoenolpyruvate is:

Answer 2

GTP

Question 3

The enzymes involved in shuttling carbons in gluconeogenesis from the mitochondria to the cytosol are called:

Answer 3

malate dehydrogenase

Question 4

High levels of ATP and citrate ___________.

Answer 4

1. inhibit glycolysis
2. indicate a high energy–well fed state
3. indicate remote gluconeogenesis.

Question 5

Phosphofructokinase (PFK) is a highly regulated enzyme. Which of the following statements about PFK are correct?

a. Acidic conditions from anaerobic metabolism activate PFK
b. AMP and ADP both bind to and stabilize the inactive conformation of F6P.
c. Citrate is an inhibitor of PFK.
d. ATP can overcome the inhibition by citrate.

Answer 5

None of the answers given is correct.

Question 6

The bifunctional enzyme is also known as __________.

Answer 6

phosphofructokinase II

Question 7

High blood sugar after a meal _______ the level of insulin released by the pancreas

Answer 7

increases

Question 8

Lactate produced in muscle tissue is converted to _________ by __________ .

Answer 8

glucose; the Cori cycle

Question 9

The primary raw materials for gluconeogenesis are:

Answer 9

lactate and amino acids.

Question 10

How many high-energy phosphate bonds are consumed in gluconeogenesis?

Answer 10

Six

Question 11

Glycerol, lactate, and amino acids contribute carbon precursors in the formation of glucose; however, the path that glycerol takes is striking different from the other precursors. Explain how it differs.

Answer 11

Glycerol enters gluconeogenesis as a breakdown product of triacylglycerols in the form of dihydroxyacetone phosphate.

Question 12

What energetic barrier prevents glycolysis from simply running in reverse to synthesize glucose?

What is the energetic cost of overcoming this barrier?

Answer 12

The reverse of glycolysis is highly endergonic under cellular conditions.

The expenditure of six NTP molecules in gluconeogenesis renders gluconeogenesis exergonic.

Question 13

Define: Lactate

Answer 13

Readily converted into pyruvate

Question 14

Define: Pyruvate carboxylase

Answer 14

Generates oxaloacetate

Question 15

Define: Acetyl CoA

Answer 15

Required for pyruvate carboxylase activity

Question 16

Define: Phosphoenolpyruvate Carboxykinase

Answer 16

Generates a high-phosphoryl-transfer-potential compound

Question 17

Define: Glycerol

Answer 17

Readily converted into DHAP

Question 18

Define: Fructose1,6-bisphosphatase

Answer 18

Gluconeogenic counterpart of PFK

Question 19

Define: Glucose 6-phosphatase

Answer 19

Found predominantly in liver

Question 20

What reactions of glycolysis are not reversible under intracellular conditions?

How are these reactions bypassed in gluconeogenesis?

Answer 20

In glycolysis, the formation of pyruvate and ATP by pyruvate kinase is irreversible. This step is bypassed by two reactions in gluconeogenesis:

1. The formation of oxaloacetate from pyruvate and CO2 by pyruvate carboxylase
2. the formation of phosphoenolpyruvate from oxaloacetate and GTP by phosphoenolpyruvate carboxykinase.

The formation of fructose 1,6-biphosphate by phosphofrutokinase is bypassed by fructose 1,6-bisphosphatase in gluconeogenesis, which catalyzes the conversion of fructose 1,6-bisphosphate into fructose 6-phosphate.

Finally, the hexokinase-catalyzed formation of glucose 6-phosphate in glycolysis is bypassed by glucose 6-phosphatase, but only in the liver.

Question 21

Avidin, a 70-kDa protein in egg white, has very high affinity for biotin. In fact, it is a highly specific inhibitor of biotin enzymes. Which of the following conversions would be blocked by the addition of avidin to a cell homogenate?

a. Glucose –> pyruvate
b. Pyruvate –> Glucose
c. Oxaloacetate –> Glucose
d. Malate –> Oxaloacetate
e. Pyruvate –> Oxaloacetate
f. Glyceraldehyde 3-phosphate –> fructose 1,6-bisphosphate

Answer 21

b. Pyruvate –> Glucose

e. Pyruvate –> Oxaloacetate

Question 22

Gluconeogenesis takes place during intense exercise, which seems counterintuitive.

Why would an organism synthesize glucose and, at the same time, use glucose to generate energy?

Answer 22

The synthesis of glucose during intense exercise provides a good example of interorgaan cooperation in higher organisms. When muscle is actively contracting, lactate is produced from glucose by glycolysis. The lactate is released into the blood and absorbed by the liver, where it is converted by gluconeogenesis into glucose. The newly synthesized glucose is then released and taken up by the muscle for energy generation.

Question 23

Liver is primarily a gluconeogenic tissue, whereas muscle is primarily glycolytic. Why does this diversion of labor make good physiological sense?

Answer 23

Muscle is likely to produce lactic acid during contraction. Lactic acid is a strong acid and must not accumulate in muscle or blood. Liver removes the lactic acid from the blood and converts it into glucose. The glucose can be released into the blood or stored as glycogen for later use.

Question 24

Why does the lack of glucose 6-phosphatase activity in the brain and muscle make good physiological sense?

Answer 24

Glucose is an important energy source for both tissues and is essentially the only energy source for the brain. Consequently, these tissues should never release glucose. Glucose release is prevented by the absence of glucose 6-phosphatase.