2 Pyruvate Kinase

Abstract

The chapter discusses the regulatory phosphorylation of pyruvate kinase type L by cAMP-dependent protein kinase. It also briefly discusses the role of phosphorylation of liver pyruvate kinase in the regulation of glycolysis and gluconeogenesis. The phosphorylation of liver pyruvate kinase alters the kinetic behavior of the enzyme, including the influence of allosteric effectors on the enzyme. The dephosphorylation of pyruvate kinase is mainly accounted for by protein phosphatase-2A. For the phosphorylation of the enzyme by cAMP-dependent protein kinase, the structural requirements reside mainly in the amino acid sequence of the phosphorylatable site. As its counterpart in the liver, kidney pyruvate kinase—type L—is phosphorylated on serine residues upon incubation with ATP and cAMP-dependent protein kinase. The phosphorylation of the pyruvate kinase and the changes of its activity are reversed by phosphoprotein phosphatase. In vivo and in isolated hepatocytes, the enzyme is subject to the same functional changes in the presence of glucagon or cAMP as the purified enzyme when it is incubated with cAMP-dependent protein kinase and ATP. The degree of phosphorylation appears to correlate fairly well with the changes in the kinetic properties of the enzyme in vitro and with the hormonal response and cAMP level in intact cells.