Question

Glycolysis and gluconeogenesis are opposite pathways. What are three different ways that the pathways are kept from canceling each other out?

Answer 1

The levels of fructose 2,6 bisphosphate in the liver is low during starvation and is high in fed state. It strongly stimulate phosphofructokinase and inhibits fructose 1,6 bisphosphatase. As the levels of fructose 2,6 bisphosphatase is high in fed state the glycolysis is accelerated and gluconeogenesis is dimnished. The opposite happens in starvation as the levels of fructose 2,6 bisphosphatase is low.

Pyruvate kinase is controlled by allosteric effectors and by phosphorylation. Pyruvate carboxylase, which catalyzes the first step in gluconeogenesis from pyruvate, is activated by acetyl CoA and inhibited by ADP. ADP inhibits phosphoenolpyruvate carboxykinase. Hence, gluconeogenesis is favored when the cell is rich in biosynthetic precursors and ATP.

Insulin stimulates the expression of phosphofructokinase, pyruvate kinase, and the bifunctional enzyme that makes and degrades Fructose 2,6-Bisphosphate. Glucagon inhibits the expression of these enzymes and stimulates instead the production of two key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and fructose 1,6-bisphosphatase.