Chapter 17 - Gluconeogenesis

Question 1

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

What is the energetic cost of overcoming this barrier?

Answer 1

The reverse of glycolysis is highly endergonic under cellular conditions.

The expenditure of six NTP molecules in gluconeogenesis renders gluconeogenesis exergonic

Question 2

What reactions of glycolysis are not reversible under intracellular conditions?

How are these reactions bypassed in gluconeogenesis?

Answer 2

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-bisphosphate by phosphofructokinase is bypassed by fructose 1,6-bisphosphatase in gluconeogenesis, which catalyzes the conversion of fructose 1,6-bisphosphate into fructose 6-phosphate

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

Question 3

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 3

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 onto glucose. The newly synthesized glucose is then released and taken up by the muscle for energy generation.

Interorgan cooperation

Question 4

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

Answer 4

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 5

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

Answer 5

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.

Question 6

Compare the roles of lactate dehydrogenase in gluconeogenesis and in lactic acid fermentation

Answer 6

In gluconeogenesis, lactate dehydrogenase synthesizes pyruvate from lactate.

In lactic acid fermentation, the enzyme synthesizes lactate from pyruvate

Question 7

In starvation, protein degradation takes place in muscle. Explain how this degradation might affect gluconeogenesis in the liver.

Answer 7

Some of the amino acids will be released into the blood. The liver will take up the amino acids and convert the carbon skeletons into glucose.

Question 8

How many NTP molecules are required for the synthesis of one molecule of glucose from two molecules of pyruvte?

Answer 8

6 NTP (4 ATP and 2 GTP)

Question 9

How many NADH molecules are required for the synthesis of one molecule of glucose from two molecules of pyruvate?

Answer 9

2 NADH

Question 10

How many NTP molecules are required to synthesize glucose from Glucose 6-phosphate

Answer 10

None

Question 11

How many NTP molecules are required to synthesize glucose from Fructose 1,6-biphosphate?

Answer 11

None

Question 12

How many NTP molecules are required to synthesize glucose from two molecules of oxaloacetate?

Answer 12

4 (2 ATP and 2 GTP)

Question 13

How many NTP molecules are required to synthesize glucose from two molecules of dihydroxyacetone phosphate?

Answer 13

none

Question 14

What are the two potential substrate cycles in the glycolytic and gluconeogenic pathways?

Answer 14

One cycle would require the glycolytic enzyme phosphofructokinase and the gluconeogenic enzyme fructose 1,6-bisphosphatase.

The other cycle would require pyruvate kinase from glycolysis and pyruvate carboxylase and phosphoenolpyruvate carboxykinase from gluconeogenesis.

Question 15

What is the regulatory role for the substrate cycles in glycolysis and gluconeogenesis?

Answer 15

The substrate cycles regulate flux on one or the other pathway by amplifying metabolic signals.

Question 16

Describe the reciprocal regulation of gluconeogenesis and glycolysis

Answer 16

The enzymes in two substrate cycles are control points.

The glycolytic pathway is activated by F-2,6-BP, AMP, and F-1,6-BP. whereas STP, alanine, citrate, and protons inhibit glycolysis.

Gluconeogenesis is activated by citrate and acetyl CoA and inhibited by F-2,6-BP, AMP and ADP

Question 17

How might enzymes that remove amino groups from alanine and aspartate contribute to gluconeogenesis?

Answer 17

If the amino groups are removed from alanine and aspartate, the ketoacids pyruvate and oxaloacetate are formed. Both of these molecules are components of the gluconeogenic pathway.

Question 18

Why is the conversion of lactic acid from the blood into glucose in the liver in an organism’s best interest?

Answer 18

Lactic acid is capable of being further oxidized and is thus useful energy. The conversion of this acid into glucose saves the carbon atom for future combustion