Gluconeogenesis

Question 1

What is Gluconeogenesis

Answer 1

Anabolic pathway converting pyruvate to glucose

Question 2

Where does it occur?

Answer 2

Occurs partially in mitochondria and partially in cytoplasm of liver and kidneys

Question 2

Is Gluconeogenesis simple reversal of glycolysis?

Answer 2

No, since need to work around the irreversible steps of glycolysis

Question 2

How many rxns in Gluconeogenesis are reversible?

Answer 2

7 glycolytic rxns are reversible, 3 are not

Question 3

Substrates for Gluconeogenesis

Answer 3

Include all intermediates of glycolysis and TCA cycle

Question 3

The Cori Cycle

Answer 3

Lactate produced in muscle and RBC is used by liver to produce glucose

Question 3

Most important substrates?

Answer 3

1. Glycerol- breakdown of lipids
2. Lactate- released into blood from red blood cells and excercising muscles (Cori cycle)
3. Amino Acids- released from breakdown of proteins and converted into a-keto acids during amino acid metabolism

Question 4

How is Pyruvate converted to oxaloacetate?

Answer 4

• Pyruvate carboxylase uses biotin as an activated CO2 carrier
• Biotin is cov. attached prosthetic group to enzyme

Question 4

Reactions unique to Gluconeogenesis?

Answer 4

1. Conversion of pyruvate to oxaloacetate
2. Formation of phosphoenolpyruvate
3. Desphosphorylation of fructose 1,6-BP
4. Dephosphorylation of glucose 6-P

Question 4

How many rxns req. to bypass irreversible steps?

Answer 4

4 rxns

Question 4

Step1- Conversion of Pyruvate to Oxaloacetate

Answer 4

• occurs in mitochondria
• CO2 is added to pyruvate to form oxaloacetate
• Req. energy in the form of ATP
• Key regulatory step; activated by acetyl-CoA

Question 5

Step 2- Transport of oxaloacetate to the cytoplasm

Answer 5

• oxaloacetate is shuttled to cytoplasm and then converted to PEP
• this rxn uses GTP as energy/phosphate donor

Question 6

3- Dephosphorylation of Fructose 1,6-BP

Answer 6

• Fructose 1,6-BP catalyzes this step
• allosteric regulatory enzyme (PFK-1 counterpart)

Question 7

Where does conversion of fructose 6-phosphate converted to glucose 6-phosphate occur?

Answer 7

Occurs in all tissues but liver gluconeogenesis stops here

Question 8

4- Dephosphorylation of Glucose

Answer 8

• Glucose 6-P transferred to lumen of ER (in liver/kidney cells)
• GLucose 6-P hydrolyzed to Glucose by glucose 6-P

Question 8

Reactant/Product of Gluconeogenesis

Answer 8

• 4 ATP and 2 GTP required
• Produces 1 molecules of glucose from 2 pyruvate

Question 9

Regulation of Gluconeogenesis is reciprocal to glycolysis

Answer 9

• molecule that activates glycolysis, inhibits gluconeogenesis

Question 10

Synthesis of Fructose 2,6-BP

Answer 10

PFK-2/FBP2 as two catalytic domains
1. PFK-2 domain= kinase domain-adds P
2. FBPase2 domain= phosphatase domain- removes P
(when 1 domain is active the other is inactive)

Question 10

Kinase domain phosphorylates fructose 6-P to form fructose 2,6-BP

Answer 10

This is a potent activator of PFK/glycolysis (inhibit gluconeogenesis)

Question 11

FBPase2 domain removes P from fructose 2,6-BP to form fructose 6-P

Answer 11

This inhibits glycolysis and activates gluconeogenesis

Question 12

When blood glucose is low, PFK-2 is phosphorylated and inhibited

Answer 12

Glucagon stimulates PKA when blood glucose is scarce. FBPase 2 is activated
- glycolysis inhibited
- gluconeogenesis activated

Question 12

When glucose is high, PFK-2 is dephosphorylated activating it

Answer 12

• high levels of fructose 6-P stimulate phosphoprotein phosphatase
• glycolysis is stimulated
• gluconeogenesis is inhibited