Gluconeogenesis Flashcards
What is Gluconeogenesis?
It is the process by which glucose is derived from pyruvate
Where is the major site of gluconeogenesis?
The major site of gluconeogenesis is the liver (Can also occur in the kidney)
When is gluconeogenesis important?
Gluconeogenesis is especially important during
fasting or starvation
What are the steps of gluconeogenesis? (exclusive steps only)
- Pyruvate into oxaloacetate
- Oxaloacetate into phosphoenolpyruvate
3-8. Reversed glycolysis steps using the same enzymes - Fructose 1,6-bisphosphatase to Fructose 6-phosphatase (Using a new enzyme)
- Reversed glycolysis steps using the same enzymes
- Glucose 6-phosphate into glucose (Using a new enzyme)
Which enzymes are found in gluconeogenesis but not in glycolysis.
- Pyruvate Carboxylase
- Phosphoenolpyruvate Carboxykinase
- Fructose 1,6-bisphosphatase
- Glucose-6-Phosphatase
What are the two types of gluconeogenesis vs glycolysis regulation?
Reciprocal Regulation: When one pathway is active the other is inhibited
Positive Effectors for Glycolysis (AMP, F-2,6-BP, F-1,6-BP) Negative effectors for Glycolysis (ATP, Alanine, Citrate, H+, G6P)
Positive Effectors for Gluconeogenesis (Citrate, Acetyl-CoA)
Negative effectors for Gluconeogenesis (ADP, AMP, F-2,6-BP)
What are the three key enzymes for gluconeogenesis?
- Pyruvate carboxylase
- FBPase
- Glucose-6-phosphatase
What is the key regulator of glucose metabolism in the liver?
Fructose 2,6-bisphosphate (Stimulates phosphofructokinase and inhibits fructose 1,6-bisphosphatase)
What is the pathway that occurs when blood glucose levels are low?
- Glucagon is released
- Phosphorylation of the PFK2-FPBase2 enzyme
- Deactivation of the kinase domain and activation of the phosphate domain
- Lowering the amount of F-2,6-BP in the cell
- Glycolysis would slow down and Gluconeogenesis would speed up
What is the pathway that occurs when blood glucose levels are high?
- Insulin is released
- Dephosphorylation of the PFK2-FPBase2 enzyme
- Activation of the kinase domain and deactivation of the phosphate domain
- Raising the amount of F-2,6-BP in the cell
- Glycolysis would speed up and Gluconeogenesis would slow down
Why is the reaction catalyzed by the pyruvate dehydrogenase complex a crucial juncture in metabolism?
The pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA, which enters the TCA cycle. (This bridges Glycolysis and the Citric Acid Cycle)
Which enzymes make up the pyruvate dehydrogenase complex? What does each one do?
Pyruvate Dehydrogenase (E1): removes a carbon from pyruvate
Dihydrolipoamide Acetyltransferase (E2): forms acetyl-CoA
Dihydrolipoamide Dehydrogenase (E3): restores the lipoamide cofactor of E2
What are the cofactors for the enzymes that make up the pyruvate dehydrogenase complex?
Pyruvate Dehydrogenase (E1): Thiamine (Vitamin B1) (TPP)
Dihydrolipoamide Acetyltransferase (E2): Lipoic acid & Coenzyme A (CoA)
Dihydrolipoamide Dehydrogenase (E3): FAD & NAD⁺
What is each cofactor responsible for in the pyruvate dehydrogenase complex?
TPP: Works with E1 to help remove a carbon from pyruvate
Lipoamide: Carries the intermediate product from E1 to E2
CoA: Joins with the intermediate from E2 to form acetyl-CoA
FAD: Helps in E3 to transfer electrons
NAD+: Picks up electrons in the final step to make NADH
How is the Pyruvate Dehydrogenase Complex regulated?
Allosteric Regulation: High levels of acetyl-CoA, NADH, and ATP inhibit the activity of the PDC, increased levels of ADP and pyruvate can activate PDC
Covalent modification: Deactivated when phosphorylated,
activated when not phosphorylated