A calcium/calmodulin-dependent protein kinase termed CaM-kinase

The nature of the protein phosphatases involved in the regulation of glycolysis/gluconeogenesis, fatty acid synthesis and cholesterol synthesis in rat liver has been investigated using L-pyruvate kinase, ATP-citrate lyase, acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase as substrates. The results show that protein phosphatases-1, 2A and 2C are the only significant protein phosphatases in rat liver acting on these four substrates. The relationship of these three enzymes to other protein phosphatases described in the literature is discussed.Glycolysis, gluconeogenesis and the synthesis of lipids (fatty acid and cholesterol) are under hormonal control; several key regulatory enzymes in these metabolic pathways are known to be controlled by phosphorylation-dephosphorylation reactions. The conversion of phosphoenolpyruvate to pyruvic acid by L-pyruvate kinase is an important control point in both glycolysis and gluconeogenesis in mammalian liver. L-pyruvate kinase is phosphorylated on a single serine residue by cyclic-AMP-dependent protein kinase, increasing its K , for phosphoenolpyruvate and decreasing its Ki for ATP and alanine.