Question

4.

a. Which steps in gluconeogenesis DO NOT occur in the cytoplasm?
b. Gluconeogenesis can synthesize glucose because it is energetically favorable in the cell. It is
energetically favorable because it bypasses the three irreversible steps of glycolysis. Which
enzymes in gluconeogenesis are involved in bypass these irreversible reactions?
c. Fructose 2,6-bisphosphate (F-2,6-BP) helps regulate both glycolysis and gluconeogenesis. F-
2,6-BP levels are determined by a single polypeptide containing both phosphofructokinase 2
(PFK2) and fructose bisphosphatase 2 (FBPase2). How is the level of F-2,6-BP regulated?

Answer 1

a. Conversion of pyruvate to oxaloacetate by pyruvate carboxylase.

Conversion of oxaloacetate to malate by malate dehydrogenase.

b. G-6-P --> G + Pi (glucose-6-phosphatase)

F-1,6-BisP --> F-6-P + Pi (Fructose-1,6-bisphosphate)

Pyr --> PEP (3 steps)

Pyr + CO2 + ATP --> oxaloacetate + ADP (occurs in mitochondria; pyruvate carboxylase)

Oxaloacetate + NADH --> malate + NAD+ (in mitochondria; malate dehydrogenase)

malate + NAD+ --> NADH + oxaloacetate (in cytoplasm; malate dehydrogenase)

Oxaloactetate + GTP --> PEP + CO2 + GDP (phosphoenolpyruvate carboxykinase).

c. The level of F-2,6-BP is regulated by synthesis and breakdown by PFK-2/FBPase-2. These two enzymes are further regulated by hormones such as insulin, glycogen and epinephrine via phosphorylation/dephosphorylation. Glucagon triggers cAMP formation which activates a protein kinase (phosphorylates PFK-2/FBPase-2 resulting in reduced level of F-2,6-BP in cells). Insulin as opposite effect as opposite to glucagon.