Regulation of pyruvate kinase, pyruvate carboxylase and PEP carboxykinase
A) In liver, pyruvate kinase is inhibited by high levels of ATP and alanine so which glycolysis is inhibited when ATP and biosynthetic intermediates are by now 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 down 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 down so pyruvate kinase is not inhibited and glycolysis will operate.
B) Pyruvate kinase is also stimulated by fructose 1, 6-bisphosphate feed- forward activation so that its activity increases when needed, as glycolysis speeds up.
c) During starvation, the priority is to conserve blood glucose for the muscle and brain. Thus, 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.