L19- Gluconeogenesis

Question 1

What is the purpose of gluconeogenesis?

Answer 1

To maintain blood glucose levels after glycogen stores have been depleted.

Question 2

In what organ(s) does gluconeogenesis occur?

Answer 2

90% in the liver and 10% in the kidneys.

Question 3

What are the three main substrates for gluconeogenesis?

Answer 3

Lactate, amino acids and glycerol.

Question 4

What are the two major end products of gluconeogenesis?

Answer 4

Glucose and glucose-6-phosphate.

Question 5

Most gluconeogenic enzymes are the same as the glycolytic enzymes. Which gluconeogenic enzymes are specific to gluconeogenesis?

Answer 5

Pyruvate carboxlyase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase.

Question 6

Describe the reactions that convert pyruvate into phosphoenolpyruvate. What is the intermediate and where in the cell do these reactions occur?

Answer 6

Pyruvate is first transported into mitochondria where it is carboxylated by pyruvate carboxylase to form oxaloacetate. The second reaction occurs in the cytoplasm but oxaloacetate cannot cross the mitochondrial membrane so it is converted to another molecule that can cross the membrane such as malate. Oxaloacetate is then regenerated in the cytoplasm where it is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase.

Question 7

What are the cofactors for pyruvate carboxylase?

Answer 7

Biotin, magnesium and manganous ions (note that all carboxylyases require biotin as a cofactor).

Question 8

Pyruvate carboxylyase requires an activator for enzymatic activity. What is that activator?

Answer 8

Acetyl-CoA.

Question 9

True or False. Biotin covalently binds to carboxylases and serves as a carrier of activated carbon dioxide.

Answer 9

True.

Question 10

What enzyme cleaves the bond between biotin and a protein to regenerate free biotin so it can bind to another protein?

Answer 10

Biotinidase.

Question 11

How may habitually eating raw egg whites cause biotin deficiency?

Answer 11

Egg white contain a protein called avidin that strongly binds to biotin, essentially taking biotin out of solution. This condition is very rare.

Question 12

What enzyme converts oxaloacetate to phosphoenolpyruvate and where is this enzyme found in the cell?

Answer 12

Phosphoenolpyruvate carboxykinase, which is found in the cytoplasm.

Question 13

The reaction catalyzed by the glycolytic enzyme that yields fructose-1,6-bisphosphate from fructose-6-phosphate is irreversible. What gluconeogenic enzyme catalyzes the reverse reaction?

Answer 13

Fructose-1,6-bisphosphatase.

Question 14

What enzyme hydrolyzes glucose-6-phosphate to yield glucose?

Answer 14

Glucose-6-phosphatase.

Question 15

Glucose-6-phosphate is found only in cells of which tissues?

Answer 15

The liver, intestine and kidneys.

Question 16

True or False. High levels of glucose-6-phosphate increase the activity of glucose-6-phosphatase.

Answer 16

True.

Question 17

In which cellular compartment is glucose-6-phosphatase found?

Answer 17

The endoplasmic reticulum.

Question 18

True or False. Both pyruvate carboxylase and phosphoenolpyruvate carboxykinase use ATP.

Answer 18

False. Pyruvate carboxylase uses ATP but phosphoenolpyruvate carboxykinase uses GTP.

Question 19

How many moles of pyruvate and ATP equivalents are required to synthesize one mole of glucose via gluconeogenesis?

Answer 19

2 moles of pyruvate and 6 moles of ATP equivalents.

Question 20

True or False. High levels of pyruvate and acetyl-CoA favor pyruvate carboxylase activity over pyruvate dehydrogenase.

Answer 20

True.

Question 21

Which enzyme is the main regulator involved in balancing glycolysis versus gluconeogenesis?

Answer 21

Phosphofructokinase 2/fructose-2,6-phosphatase (PFK2). It favors gluconeogenesis when phosphorylated and glycolysis when not phosphorylated.

Question 22

What are the three ways by which glucagon stimulates gluconeogenesis?

Answer 22

It stimulates the phosphorylation of pyruvate kinase, the phosphorylation of phosphofructokinase, and increases gene transcription and synthesis of other gluconeogenic enzymes.

Question 23

Why is muscle unable to synthesize glucose via gluconeogenesis?

Answer 23

The enzymes pyruvate carboxylase and glucose-6-phosphatase are not expressed in muscle.

Question 24

What is the Cori cycle?

Answer 24

It is the pathway by which muscle produces lactate during a state of energy depletion and sends it to the liver, where it can be converted back to glucose. The glucose will then get sent back to muscle to generate energy.

Question 25

What is the Cahill cycle?

Answer 25

It is the pathway by which muscle produces alanine from pyruvate during a state of energy depletion and sends it to the liver, where it can be converted back to glucose. The glucose will then get sent back to muscle to generate energy.

Question 26

What are common symptoms of gluconeogenic enzyme deficiencies?

Answer 26

Hypoglycemia between meals and acidosis, the latter of which mostly caused by accumulation of lactate.