Gluconeogensis Flashcards
Under what metabolic conditions does gluconeogenesis occur?
Starvation, exercise and diabetes
What is gluconeogenesis
The prediction of glucose from non carbohydrate sources
What are the different precursors that can produce glucose
Pyruvate, amino acids (alanine and glutamine) —> CAC intermediates
Is gluconeogenesis the direct reversal of glycolysis
No
How is pyruvate converted to PEP
There are 2 steps:
Both being exergonic reactions
- Pyruvate is converted to oxaloacetate via pryruvate carboxalate (irreversible)
2 Oxaloacetate + GTP is converted to phosphoenolpyruvate via PEPCK (PEP, reversible)
- decarboxylation and phosphate transfer
What organs express glucose-6-phosphatase?
Kidney, liver , GI
Why doesn’t muscle express glucose-6-phosphatase ?
Because the muscle doesn’t want to release glucose, therefor will not express the enzyme
How is F1,6BP converted to F6P
Hydrolysis if C1 of the phosphate ester bond by F1,6 Bisphosphatase
What enzyme does F1,6 Bisphosphatase oppose?
PFK-1
How is glucose-6-phosphate converted to glucose?
Hydrolysis of C6 to form glucose via glucose 6 phosphotase, irreversible
Where does gluconeogenesis predominately occur
In the liver and kidneys
What enzyme does G6phosphatse oppose
Glucokinase
What are the difference in the alternative pathways to forming PEP from pyruvate?
PEPCK-C
- activated by glucagon therefore is inducible
- happens in the cytosol of the cell
PEPCK-M
- is constitutive
- occurs in the mitochondria
Describe the pathway of PEPCK-C
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 )
Describe the pathway with PEPCK-M
Lactate -> pyruvate -> (pyruvate -> oxaloacetate **-> PEP) ->PEP
** PEPCK-M
What is are the inhibitors of fructose bisphosphate?
Fructose 2,6 Bisphosphate and AMP
What are the activators of PFK-1?
AMP and F2,6BP
Why is F2,6BP an important regulator in glycolysis and gluconeogenesis?
It tells us blood glucose levels, high amounts of it mean glycolysis and low amounts mean gluconeogenesis
What happens in the hepatocyte in responses to low blood glucose (use enzymes)
- Glucagon is released
- Increases activity of Protein Kinase A
- Phosphorylates FBPase-2 to decrease amount of F26BP and increase F6P
- Increase in F6P singals to PFK-1 to decrease activity, increase activity of FBPase-1
- Increase in gluconeogensis
what happens in the hepatocyte when there is an increase in blood sugar?
- Increase in blood suagr
- Increase in insulin production
- Protein phosphatase-1 which dephophorylated regulatory domain of PFK-2 (inactivates FBPase-2)
- PFK-2 converts F6P to F26BP (increase in F26BP)
- Increase in F26BP means increase in PFK-1 activity, inhibiting FBPase-1
- Increases glycolysis
What happens with the regulation of PFK-2 in the skeletal muscle?
- controlled by allosterics (PFK-2)
- High levels of F6P increases glucose uptake muscles
What regulates the activity of glucokinase in the liver
- Glucose and F1P increase the activity
- F6P decreases the activity
How is glucokinase regulated by GKRP?
- F6P enhances the binding of GK by GKRP
- Increased F6P = gluconeohgensis is active
- F1P reduces the binding of GKRP
- singals well fed state = glycolysis
What are the competivite binders of glucokinase
- glucose and GKRP
How is the binding of GKRP regulated
- 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)
