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Unformatted text preview: activity of fructose 1,6-bisphosphatase, a key enzyme in gluconeogenesis.
b) What are the unique features of phosphofructokinase 2 (PFK2) and fructose
2,6 bisphosphate phosphatase 2 (FBPase2). [Please note these enzymes are for
fructose 2,6-bisphosphate metabolism, while the substrate/product for
glycolysis/gluconeogenesis is fructose 6-phosphate and fructose 1,6bisphosphate]
These are two opposing enzymatic activities located in two different domains
in the same polypeptide chain. PFK2 is responsible for the synthesis of
3 F2,6BP, while FBPase2 catalyzes the hydrolysis of F2,6BP to F6P.
Phosphorylation and de-phosphorylation regulates the differential activities
of these two enzymes (as shown in the diagram above).
c) Explain why higher activity of FBPase2, an enzyme converting fructose 2,6
bisphosphate to fructose 6 phosphate, reduces glycolysis.
Higher activity of FBPase2 will reduce the level of F2,6BP, which in turn
cannot enhance PFK activity needed for the production for F1,6BP, a
committal step for glycolysis.
d) Explain how glucagon, whose physiological role is similar to that of
epinephrine, leads to higher level of glucose even not counting on glycogen being
Glucagon triggers the synthesis of cAMP, which activates PKA (see signaling
pathway of epinephrine).
As shown in the diagram above, PKA
phosphorylates PFK2-FBPase2 knocking out PFK2 activity, hence reducing
the level of F2,6BP, leading to slowdown in glycolysis and enhancement in
gluconeogenesis for the synthesis of glucose.
e) Explain how high levels of fructose 6 phosphate inhibit glyconeogenesis.
High levels of F6P lead to the formation of the regulator F2,6BP which in
turns inhibits F1,6 BPase, a key enzyme in gluconeogenesis.
f) What are the likely consequences of a genetic disorder rendering fructose 1, 6
bisphosphatase less sensitive to regulation by fructose 2,6 bisphosphate?
If fructose 1, 6 bisphosphatase is less sensitive to the inhibition by F2,6BP
but PFK is still activated by F2,6BP, fructose 1,6 bisphosphate tends to be
converted back to F6P even when F2,6BP level is high. This generates a
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