Gluconeogenesis Flashcards
What blood glucose concentration do we need to maintain?
4.0-5.5 mM/litre.
At what concentration may the body enter a hypoglycaemic coma?
Below 3mM.
What three measures can the body take to avoid hypoglycaemia?
Breakdown of liver glycogen stores.
Release of free fatty acids from adipose tissue.
Conversion of acetyl CoA into ketone bodies.
From our free fatty acid metabolism work, we learned that fat metabolism cannot lead to a net gain of oxaloacetate/pyruvate and so it cannot generate glucose.
Why then may the body convert acetyl CoA into ketone bodies or release free fatty acids to avoid hypoglycaemia?
While fatty acids/acetyl CoA cannot be used to synthesise glucose, that can be used by other tissues instead of glucose, freeing up more glucose for the brain to use.
Ketone bodies can also be used by the brain, and it has been suggested that the brain may be capable of surviving on ketone bodies alone.
Non-carbohydrate precursors can enter the gluconeogenesis pathway. What are these?
Glycerol from triglyceride hydrolysis (forms DHAP), some amino acids (oxaloacetate and pyruvate) and lactate (converted back to pyruvate).
Lactate can regenerate pyruvate with what enzyme?
What cycle is this apart of?
Lactate dehydrogenase (LDH) in the Cori Cycle.
Where can we derive amino acids from for gluconeogenesis?
From the diet or during times of starvation from the breakdown of skeletal muscle.
How many essentially irreversible reactions does glycolysis have and what catalyse them?
Three, catalysed by the kinases:
Hexokinase
Phosphofructokinase
Pyruvate Kinase
Which non-glycolytic enzymes do we use to bypass the irreversible reactions?
Pyruvate carboxylase to convert pyruvate into oxaloacetate.
Phosphoenolpyruvate carboxykinase to convert oxaloacetate into phosphoenolpyruvate.
Fructose-1,6-bisphosphatase to convert fructose-1,6-bisphosphatase to fructose-6-phosphate.
Glucose-6-phosphatase to convert glucose-6-phosphate to glucose.
Where do the reactions of gluconeogenesis occur?
All in the cytosol except for the conversion of pyruvate into oxaloacetate which is in the mitochondria (the first reaction working from the bottom of the pathway, some molecules will start later on in the pathway and so won’t do this step).
Why is gluconeogenesis not just the reversal of glycolysis?
The ΔG for the straight reversal of glycolysis would be +90 kJ/mol which is energetically unfavourable but thankfully the ΔG for gluconeogenesis is -38kJ/mol.
