Function of calcium ions in pyruvate dehydrogenase phosphatase activity

Abstract

Phosphorylation and dephosphorylation of the pyruvate dehydrogenase (PDH) component of the mammalian pyruvate dehydrogenase complex are catalyzed, respectively, by a MgATP 2-requiring kinase and a Mg 2+-requiring phosphatase. The kinase and the PDH, but not the phosphatase, are tightly bound to the dihydrolipoyl transacetylase core of the complex. Evidence is presented that the activity of the PDH phosphatase from bovine kidney and heart is increased about tenfold when it is attached to the transacetylase. Ca 2+ is required to bind the phosphatase, but not the kinase or the PDH, to the transacetylase, thereby facilitating the Mg 2+-dependent dephosphorylation of the phosphorylated PDH. Ca 2+ lowers the apparent K m of the phosphatase for phosphorylated PDH about twentyfold. The Ca 2+-controlled association of the phosphatase and the transacetylase could provide an important mechanism for regulation of the phosphorylation-dephosphorylation cycle.