Question

Explain in detail how PFK-1, hexokinase, glucokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase-1, pyruvate carboxylase & PEPCK are regulated & compare their regulation in liver vs. skeletal muscle & brain when blood glucose levels are high (i.e. a fed state) & low (i.e. a fasting or starvation state).

Answer 1

The rate of glycolysis is determined by the concentration of glucose, and the rate of gluconeogenesis by the concentrations of lactate and other precursors of glucose. The level of fructose 2,6-bisphosphate is high in the fed state and low in starvation. Fructose 2,6-bisphosphate strongly stimulates phosphofructokinase and inhibits fructose 1,6-bisphosphatase.Another important control is the inhibition of pyruvate kinase by phosphorylation during starvation.The interconversion of phosphoenolpyruvate and pyruvate is precisely regulated. 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.

Regulation in liver cells :

In skeletal muscle during vigorous exercise, the rate at which glycolysis produces pyruvate exceeds the rate at which the citric acid cycle oxidizes it. Continued glycolysis depends on the availability of NAD+ for the oxidation of glyceraldehyde 3-phosphate. Liver furnishes glucose to contracting skeletal muscle, which derives ATP from the glycolytic conversion of glucose into lactate. Contracting skeletal muscle supplies lactate to the liver, which uses it to synthesize glucose. These reactions constitute the Cori cycle.