Regulation of pyruvate kinase, pyruvate carboxylase and PEP carboxykinase:

-   In liver,  pyruvate  kinase  is inhibited  through high levels  of ATP and alanine  so which  glycolysis  is  inhibited  when  ATP  and  biosynthetic  intermediates   are already  plentiful.  The Acetyl CoA is also abundant under these conditions and favoring gluconeogenesis and activates pyruvate carboxylase. Conversely, when the energy status of the cell is low and the ADP concentration is high and this inhibits both pyruvate carboxylase and PEP carboxykinase, switching off gluconeogenessis. At present, the ATP level will be low so pyruvate kinase is not inhibited and glycolysis will operate.

-   Pyruvate kinase is also stimulated through fructose 1, 6-bisphosphate feed- forward activation so that its activity rises when required, as glycolysis speeds up.

-   During starvation, the priority is to conserve blood glucose for the muscle and brain. Therefore, under these situations and pyruvate kinase in the liver is switched off.  This  happens  because  the  hormone  glucagon  is secreted  into  the  blood- stream  and activates  a cAMP  cascade which leads to the inhibition and phosphorylation of this enzyme.