Question

Pyruvate kinase is a key regulatory pacemaker enzyme of animal and plant glycolysis. Describe the sequence of events (signal transduction pathway) whereby elevated glucagon concentrations in our bloodstream leads in inactivation of PK in the cytosol of hepatocytes (liver cells)

Answer 1

Elevated glucagon levels trigger a phosphorylation cascade via adenyl cyclase activation and cAMP production, leading to the inactivation of pyruvate kinase in hepatocytes, shifting liver metabolism towards glucose release.

Step-by-step explanation:

When glucagon concentrations in the bloodstream are elevated, a signal transduction pathway is initiated that ultimately leads to the inactivation of pyruvate kinase (PK) in hepatocytes. Elevated glucagon binds to its receptors on liver cells, activating adenyl cyclase. This enzyme catalyzes the conversion of ATP to cyclic AMP (cAMP). The increase in cAMP activates protein kinase A (PKA), which then initiates a phosphorylation cascade.

PKA phosphorylates pyruvate kinase kinase (PKK), which in turn phosphorylates and inactivates pyruvate kinase, the pacemaker enzyme of glycolysis. This phosphorylation results in the conversion of PK from its active 'a' form to a less-active 'b' form, decreasing glycolysis and shifting the cell's metabolism towards glucose production rather than its breakdown. The decrease in pyruvate kinase activity occurs because the liver is responding to the signal to release glucose into the bloodstream for other tissues to use, which is the opposite function of glycolysis.