Gluconeogenesis Flashcards
What two molecules can be made into pyruvate?
Alanine and lactate
Where does Gluconeogenesis occur?
Liver
Gluconeogenesis: Pyruvate is made into?
Oxaloacetate by pyruvate carboxylase
Gluconeogenesis: Oxaloacetate is made into…
Phosphoenolpyruvate by phosphoenolpyruvate carboxykinase
Glycerol is fed into the gluconeogensis pathway and…
Phosphorylated to glycerol-3-P and into Dihydroxyacetone-P and fed into Fructose 1,6-bisphosphate
In gluconeogenesis, what happens to phosphoenolpyruvate?
Made into glyceraldehyde 3 P
Gluconeogenesis: Glyveraldehyde 3 P is made into?
Fructose 1,6-bisphosphate
Gluconeogenesis: What happens to Fructose 1,6 bisphosphate?
Taken to Fructose 6-phosphate via fructose 1,6-bisphosphatase
Gluconeogensis: What happens to fructose 6-phosphate?
Taken to glucose 6-phosphate
Gluconeogenesis: What happens to glucose 6-phosphate?
Taken to glucose by glucose 6-phosphatase
How many irreversible steps are there in gluconeogenesis?
3
How many ATP equivalents are needed for gluconeogenesis?
6 ATP
What three steps in gluconeogenesis are irreversible?
Pyruvate to oxaloacetate (2 ATP via pyruvate carboxylase), Oxaloacetate to Phosphoenolpyruvate (PEP carboxykinase, 2 GTP) and Glucose 6-P to glucose (glucose 6-phosphatase)
Lactate is made to pyruvate via?
Lactate dehydrogenase and via oxidation of NADH
How is alanine made into pyruvate?
Via alanine aminotransferase
What is the difference between gluconeogensis in aerobic and anaerobic conditions?
Aerobic has no NADH and anaerobic has NADH available
Where is NADH used in gluconeogensis?
2 NADH to 2 NAD in 2 1,3-bisphophate to Glyceraldehyde 3-P
Pyruvate to Oxaloacetate requires?
CO2, ATP, Biotin, and pyruvate carboxylase
Gluconeogenesis: T or F: Pyruvate carboxylase happens exclusively in the mitochondria
T
Describe the aerobic pathway of gluconeogensis to PEP
Pyruvate into mitochondria, Pyruvate to Oxaloacetate, Oxaloacetate to Malate with 1 NADH to NAD, Malate out of mitochondria, malate to oxaloacetate via cystolic malate dehydrogenase, then cystolic PEP carboxykinase to PEP
Describe anaerobic gluconeogenesis to PEP
Lactate to Pyruvate vis lactate dehydrogenase producing NADH, Pyruvate into mitochondria, Pyruvate to Oxaloacetae via pyruvate carboxylase, then mitochondrial PEP carboxykinase to PEP, PEP out
Where is PEP carboxykinase found?
Both in cytosol and in mitochondria
In anaerobic PEP formation, where is PEP made?
Mitochondria
In aerobic gluconeogensis, where is PEP made?
Cytosol
Which enzyme for gluconeogenesis is primarily found in the liver?
Glucose 6-phosphatase
What are the 4 bypass enzymes for gluconeogenesis?
Pyruvate carboxylase (driven by acetyl CoA), PEP carboxylase, Fructose 1,6 bisphosphatase, and glucose 6-phosphatase
PEP carboxylase and pyruvate carboxylase are regulated by?
Positive: Acetyl CoA, glucagon, epinephrine, glucocorticoids
Negative: Insulin
Fructose 1,6 bisphosphatase is regulated by?
Positive: during fasting
Negative: F-2,6-P, AMP
Glucose 6-phosphatase is regulated by?
Positive: Fasting
In the liver, describe cAMP cascade for glucagon/epinephrine
cAMP activates PKA which phosphorylates PFK-2 to the inactive mode activating FBP-2 of the bienzyme. This decreases Fructose 2,6 bisphophate which stops inhibition of fructose bisphosphatase 1 allowing Fructose 6-phosphate to be made
Glucagon is present in liver
cAMP activated = P of PFK2/FBP 2 = decreased F2,6BP = decreased glycolysis/increased gluconeogensis
Insulin in the liver…
cAMP deactivated = dP of PFK 2/FBP2 = increased F2,6BP = increased glycolysis/decreased gluconeogenesis
T or F: Muscle has glucagon receptors
F, just epinephrine and insulin
Epinephrine in muscle
cAMP activated = P of PFK2/FBP2 = activates production of F2,6BP = increases glycolysis!!
Insulin in muscle…
cAMP turned off, dP of PFK2, decreases F2,6BP which decreases glycolysis
Why is the effect of P in the PFK2/FBP2 enzymes different in muscle/liver?
Different isozymes. P in muscle activates PFK2, P in liver deactivates PFK2
What is the cori cycle?
Reconversion of lactate to glucose by the liver
How does the cori cycle work?
Lactate in blood taken up by liver and undergoes gluconeogensis and glucose is sent to RBC where it undergoes glycolysis to make more lactate
Why is drinking alcohol on an empty stomach bad?
Ethanol makes a lot of NADH which then makes lots of malate and lactate which prevents Gluconeogensis starving brain of glucose
