Gluconeogensis

Question 1

Under what metabolic conditions does gluconeogenesis occur?

Answer 1

Starvation, exercise and diabetes

Question 2

What is gluconeogenesis

Answer 2

The prediction of glucose from non carbohydrate sources

Question 3

What are the different precursors that can produce glucose

Answer 3

Pyruvate, amino acids (alanine and glutamine) —> CAC intermediates

Question 4

Is gluconeogenesis the direct reversal of glycolysis

Answer 4

No

Question 5

How is pyruvate converted to PEP

Answer 5

There are 2 steps:
Both being exergonic reactions

1. Pyruvate is converted to oxaloacetate via pryruvate carboxalate (irreversible)
   2 Oxaloacetate + GTP is converted to phosphoenolpyruvate via PEPCK (PEP, reversible)
   - decarboxylation and phosphate transfer

Question 6

What organs express glucose-6-phosphatase?

Answer 6

Kidney, liver , GI

Question 7

Why doesn’t muscle express glucose-6-phosphatase ?

Answer 7

Because the muscle doesn’t want to release glucose, therefor will not express the enzyme

Question 8

How is F1,6BP converted to F6P

Answer 8

Hydrolysis if C1 of the phosphate ester bond by F1,6 Bisphosphatase

Question 9

What enzyme does F1,6 Bisphosphatase oppose?

Answer 9

PFK-1

Question 10

How is glucose-6-phosphate converted to glucose?

Answer 10

Hydrolysis of C6 to form glucose via glucose 6 phosphotase, irreversible

Question 11

Where does gluconeogenesis predominately occur

Answer 11

In the liver and kidneys

Question 12

What enzyme does G6phosphatse oppose

Answer 12

Glucokinase

Question 13

What are the difference in the alternative pathways to forming PEP from pyruvate?

Answer 13

PEPCK-C
- activated by glucagon therefore is inducible
- happens in the cytosol of the cell

PEPCK-M
- is constitutive
- occurs in the mitochondria

Question 14

Describe the pathway of PEPCK-C

Answer 14

Pathway is used during starvation, when glucagon is released
Alanine ->(Pyruvate -> oxaloacetate -NADH TO NAD+-> malate) -> malate -NAD+ TO NADH-> oxaloacetate -**> PEP (+CO2)
**increase in glucagon means INC PEPCK, pulling the pathway

(With in the cell )

Question 15

Describe the pathway with PEPCK-M

Answer 15

Lactate -> pyruvate -> (pyruvate -> oxaloacetate **-> PEP) ->PEP
** PEPCK-M

Question 16

What is are the inhibitors of fructose bisphosphate?

Answer 16

Fructose 2,6 Bisphosphate and AMP

Question 17

What are the activators of PFK-1?

Answer 17

AMP and F2,6BP

Question 18

Why is F2,6BP an important regulator in glycolysis and gluconeogenesis?

Answer 18

It tells us blood glucose levels, high amounts of it mean glycolysis and low amounts mean gluconeogenesis

Question 19

What happens in the hepatocyte in responses to low blood glucose (use enzymes)

Answer 19

1. Glucagon is released
2. Increases activity of Protein Kinase A
3. Phosphorylates FBPase-2 to decrease amount of F26BP and increase F6P
4. Increase in F6P singals to PFK-1 to decrease activity, increase activity of FBPase-1
5. Increase in gluconeogensis

Question 20

what happens in the hepatocyte when there is an increase in blood sugar?

Answer 20

1. Increase in blood suagr
2. Increase in insulin production
3. Protein phosphatase-1 which dephophorylated regulatory domain of PFK-2 (inactivates FBPase-2)
4. PFK-2 converts F6P to F26BP (increase in F26BP)
5. Increase in F26BP means increase in PFK-1 activity, inhibiting FBPase-1
6. Increases glycolysis

Question 21

What happens with the regulation of PFK-2 in the skeletal muscle?

Answer 21

• controlled by allosterics (PFK-2)
• High levels of F6P increases glucose uptake muscles

Question 22

What regulates the activity of glucokinase in the liver

Answer 22

• Glucose and F1P increase the activity
• F6P decreases the activity

Question 23

How is glucokinase regulated by GKRP?

Answer 23

• F6P enhances the binding of GK by GKRP
• Increased F6P = gluconeohgensis is active
• F1P reduces the binding of GKRP
• singals well fed state = glycolysis

Question 24

What are the competivite binders of glucokinase

Answer 24

• glucose and GKRP

Question 25

How is the binding of GKRP regulated

Answer 25

• Phosphorylation of GKRP by AMPK reduces the binding of glucokinase by GKRP
• AMPK is active in the presence of increased AMP (signal low energy levels therefore enhanced glycolysis)