Gluconeogenesis Flashcards
What is gluconeogenesis? Where does it occur?
Formation of glucose from pyruvate and other precursors in the liver. Antiparallel to glycolysis.
What is special about the brain and RBCs energy use?
They only use glucose for energy
When does gluconeogenesis occur? What does this have to do with starvation, and what is the problem with this?
Occurs when glycogen is depleted–often due to starvation or heavy exercise. However, gluconeogenesis requires energy–hydrolyzes 6 Pi bonds.
What are the precursors for gluconeogenesis?
Pyruvate, lactate, alpha-keto acids, glycerol, certain amino acids.
Latter are usually converted to pyruvate–reaction starts with pyruvate.
Alternatively, can be converted to oxaloacetate, and rxn can proceed.
How many reactions does gluconeogenesis share with glycolysis?
7
Does not share the 3 irreversible reactions–uses different enzymes
What are the 3 bypass reactions in gluconeogenesis?
1) Pyruvate -> phosphoenolpyruvate, via pyruvate carboxylase and pyruvate carboxykinase
2) fructose-1,6,-bisphosphate -> fructose-6-phosphate, via fructose-1,6-bisphosphatase
3) glucose-6-phosphate -> glucose, via liver and kidney specific enzyme glucose-6-phosphatase
What are the most common non-pyruvate precursors?
Lactate, glycerol, alanine
What is the Cori cycle?
glucose -> lactate and lactate -> glucose cycle.
Lactate is produced by anaerobic fermentation in the muscles and RBCs. It is released in blood and taken to liver.
In the liver, lactate dehydrogenase converts it to pyruvate. Pyruvate undergoes gluconeogenesis.
How does gluconeogenesis from glycerol work?
Glycerol is converted to DHAP and can enter the gluconeogenesis pathway.
How does gluconeogenesis from alanine work?
Alanine is generated from pyruvate in exercising muscle.
Then it is converted to pyruvate in liver, and enters gluconeogenesis.
What are the functions of the glucose-alanine cycle?
1) Recycles alpha-ketoacids (pyruvate and alpha-ketoglutarate) between muscle and liver
2) Transports amino-N to liver, where it is eliminated as urea
What enzymes regulate gluconeogenesis? Glycolysis?
Gluconeogenesis:
1) pyruvate carboxylase
2) pyruvate carboxykinase
3) fructose-1,6-bisphosphatase
4) glucose-6-phosphatase
Glycolysis:
1) hexokinase
2) PFK-1
3) pyruvate kinase
How does insulin regulation work?
High glucose stimulates insulin release from pancreatic beta-islet cells
Insulin stimulates glucose uptake and glycolysis
Increases fructose-2,6-bisphosphate level
Upregulates transcription of hexokinase, pyruvate kinase, PFK
Downregulates glucose-6-phosphatase, fructose-1,6-bisphosphatase, pyruvate carboxylase and carboxykinase
How does insulin regulation increase F-2,6-BP level?
When glucose is high, PFK-2 is active and synthesizes F-2,6-BP from F-6-P.
When glucose is low, PFK-2 is phosphorylated and doesn’t synthesize. Instead acts as a phosphatase.
How does glucagon regulation work?
Low blood glucose stimulates glucagon release from pancreatic alpha cells.
Stimulates gluconeogenesis. Reduces F-2,6-BP level.
Increases cAMP level. cAMP activates cAMP dependent protein kinase, which phosphorylates PFK-2, causing it to reduce F-2,6-BP synthesis.
This stimulates gluconeogenesis. Increases transcription of gluconeogenesis enzymes and reduces transcription of glycolysis enzymes.
