Question

Research in cell biology and metabolism has progressed due to the discovery of molecules that artificially stimulate or inhibit glucagon/epinephrine and insulin signaling pathways. Let’s say you are working in a lab cataloging the effects of a library of small molecules on these pathways and have a “hit” on molecule 1stAVNGR. Preliminary data on molecule 1stAVNGRindicates that the cardiac isoform of PFK2/FBPase2 is doubly phosphorylated when this molecule is present at micromolar concentrations in cell cultures. A. In consideration of the data presented in this problem what would be the expected effect of molecule 1stAVNGRon glycolytic flux in a culture of cardiac myocytes? Explain your reasoning? B.Finally, if molecule 1stAVNGRwere infused into a culture of hepatocytes what would be the expected effect on glycolytic flux in these cells? Explain your reasoning.

Answer 1

Phosphorylation of PFK2/FBPase2 in the presence of the molecule, activates PFK2 in heart (cardiac cells) which in turn stimulates glycolysis. PFK2 controls the glycolytic pathway through inhibition of PFK1.

Presence of the molecule will induce phosphorylation of PFK2/FBPase 2 and this phosphorylation, in liver cells, result in the activation of FBPase 2. Activation of FBPase 2 results in the decrease of fructose 2,6 biphosphate levels thereby decreasing the concentration of PFK1. This leads to inhibition of glycolysis and activation of gluconeogenesis.