GLuconeogenesis Flashcards
4 important enzymes to know details about regarding gluconeogenesis
- Glucose 6 phosphate (ER)
- Fructose 1,6 -Bisphosphatase (cytosol)
- PEPCK (Cytosol)
- Pyruvate Carboxylase (Mitochondrial matrix)
Pyruvate carboxylase regulation
catalyzes the carboxylation of pyruvate to make oxallo acetate.
Pyruvate carboxylase is located ? and requires?
mito matrix
biotin
run driven by ATP hydrolysis
PEPCK does what
turns OAA into PEP (driven by GTP hydrolysis )
Fructose 1,6, Bis Pase does what?
Turns Fructose 1,6,-Bisphosphatase into Fructose 6 phosphate
G6Pase does what ?
G6P into glucose
B oxidation provides what
ATP and NADH
Pyruvate carboxylase is allosterically activated by what?
Ace-COA increases with fasting (B-ox) so it says “make more glucose”
Phosphoenolpyruvate Carboxykinase regulation
regulated by gene expression
–activated by epi, cortisol, which activate PKA which activated PEPCK
Fructose 1,6, Bis phosphatase is inhibited and activated by ?
A : ATP and citate
I: AMP and F 2,6, BP
How are the levels of Fructose 2,6-Bisphosphate regulated?
By 2 enzymes of the same polypeptide (FBPase2 and PFK2) . When the bifunctional protein is phosphorylated then PBPase2 dominates and lowers the levels of Fructose 2,6,-BisP and raising levels of Fructose 6,P. Which activates the gluconeogenic pathway. What phosphorylates the bifunctional protein ? PKA does ..
Follow this ,, Fasting ups PKA which leads to phosphorylation of the bifunctional protein. Then you increase the activity of the FBPase enzyme and lower the levels of F-2,6, BP. This allows fructose 1,6 bisphosphatatase to be more active. At the same time , this will decrease the activity of the glycolytic enzyme .
The reverse is also true .. when the bifunctional protein is not phosphorylated , then the PFK2 enzyme dominates leading to an increase in Fructose 2,6-BisP. and a decrease in Fructose -6,P. With an increase F-2,6-BisP, this inhibits the activity of the gluconeogenic pathway and activates the glycolytic pathway.
So, when we are not fasting, (high blood glucose) then PKA will be low. The bifunctional protein will not be phosphorylated. That is why the PFK2 enzyme dominates thus leading to increased F-2,6, Bis P. which increases the glycolytic pathway.
Regulation of G6Pase.
Regulated at gene expression. Induced expression by glucagon, epi, and cortisol. These all activate PKA which activates Glucose 6-phosphatase.
General rule of PKA regulation relating to gluconeogenic and glycolytic pathway
up regulate glujconeogeneis and down regulate glycolysis.
Drinking on an empty stomach ..
depletes the body of NAD+ and gives it too much NADH
Von Gierke’s Disease
Defect in glucose 6-phosphatase.
can’t rid of liver glycogen.
Defects in carriers transporting G6P, glucose , or Pi across the ER membrane have similar phenotypes.