L8 - Gluconeogenesis

Question 1

During what situations is gluconeogenesis active?

Answer 1

Fasting, or fight/flight situations

Question 2

What percentage of gluconeogenesis is performed by the liver and the kidney? How does this change during prolonged starvation?

Answer 2

Normally 90% liver and 10% in kidneys; during prolonged starvation this changes to 60/40.

Question 3

Where are most GNG enzymes found?

Answer 3

In the cytosol.

Question 4

Three of the enzymes in GNG are found outside of the cytosol. What are these enzymes and where are they found?

Answer 4

Glucose 6-phosphatase (in smooth ER membrane)
Pyruvate carboxylase (mitochondria)
PEP carboxykinase (mitochondria and cytosol)

Question 5

Which GNG enzyme bypasses glucokinase?

Answer 5

glucose 6-phosphatase

Question 6

Which GNG enzyme bypasses PFK-1?

Answer 6

Fructose 1,6-bisphosphatase

Question 7

Which two GNG enzymes bypass pyruvate kinase?

Answer 7

pyruvate carboxylase and PEP carboxykinase

Question 8

GNG and glycolysis both take place in the liver; however, they do not predominate in the same cells. Which cells does GNG predominate in? Which cells does glycolysis predominate in?

Answer 8

GNG - periportal cells

glycolysis - perivenous cells

Question 9

Pyruvate carboxylase catalyzes the conversion of what?

Answer 9

Pyruvate to oxaloacetate

Question 10

PEP carboxykinase catalyzes the conversion of what?

Answer 10

Oxaloacetate to PEP

Question 11

Fructose 1,6-bisphosphatase catalyzes the reaction of what?

Answer 11

fructose 1,6-bisphosphate to fructose 6-phosphate

Question 12

Glucose 6-phosphatase catalyzes which reaction of GNG?

Answer 12

Last reaction: G6P to glucose

Question 13

How does acetyl CoA figure into GNG? Where does it come from in gluconeogenesis?

Answer 13

Allosteric activator of pyruvate carboxylase. Comes from beta-oxidation

Question 14

What are the two functional domains of the bifunctional enzyme PFK-2?

Answer 14

1) PFK-2

2) FBPase-2

Question 15

What are the three starting substrates that can form glucose in GNG? And where do they come from?

Answer 15

1) amino acids, alanine and glutamine
2) lactate, from Cori cycle
3) glycerol, from TAG degradation

Question 16

What is the glucose-alanine cycle? What does it provide and what does it start with?

Answer 16

The glucose-alanine cycle starts with alanine from muscle proteolysis, and returns glucose to the muscles by GNG in the liver (converts alanine to glucose)

Question 17

What is the Cori cycle? Where does it take place? What is its purpose?

Answer 17

The Cori cycle takes lactate from muscle and turns it into glucose through hepatic GNG to provide glucose for muscles in anaerobic conditions

Question 18

What enzyme turns pyruvate into alanine?

Answer 18

Alanine aminotransferase (ALT)

Question 19

Alanine aminotransferase uses which two amino acids as cosubstrates?

Answer 19

1) alpha-ketoglutarate

2) glutamate

Question 20

Where is pyruvate carboxylase found? What are its cofactors/cosubstrates?

Answer 20

1) mitochondria

2) biotin, CO2, ATP, and pyruvate

Question 21

Where is PEP carboxykinase found? What reaction does it catalyze? How does the reactant get to the cytosol from the mitochondrion?

Answer 21

1) cytosol
2) OAA to PEP
3) malate shuttle

Question 22

What is special about PEP carboxykinase?

Answer 22

It uses GTP instead of ATP

Question 23

What enzyme is deficient in Von Gierke disease? What is another name for this disease? What metabolic process can not be performed?

Answer 23

1) glucose 6-phosphatase
2) glycogen storage disease, type 1
3) gluconeogenesis

Question 24

Which two molecules inhibit fructose 1,6 bisphosphatase?

Answer 24

1) AMP

2) fructose 2,6-bisphosphate

Question 25

The bifunctional enzyme PFK-2/FBPase-2 can be phosphorylated/dephosphorylated. Which domain is the phosphate removed/put on? Which molecule stimulates phosphorylation? Which dephosphorylation?

Answer 25

1) PFK-2
2) Glucagon stimulates dephosphorylation which INHIBITS PFK-2 and stimulates FBPase-2
3) Insulin stimulates phosphorylation which ACTIVATES PFK-2 and inhibits FBPase-2

Question 26

What are the energy requirements for GNG?

Answer 26

4 ATP, 2 GTP, and 2 NADH

Question 27

The liver can perform both GNG and this metabolic process simultaneously.

Answer 27

beta-oxidation