| Abstract: | In polymorphonuclear leukocytes from severely diabetic patients the rate of glycolysis is decreased due to decreased activity of phosphofructokinase, and the glycogen content and rate of glycogen synthesis are decreased due to a decreased total activity of glycogen synthase and an impaired activation of this enzyme. Covalent modification of glycogen synthase by phosphorylation creates a continuum of phosphorylated enzyme forms of decreasing activity. Phosphorylation of a single peptide, whether by the synthase kinase or the cyclic AMP dependent protein kinase, is critical for the associated kinetic changes during the initial phosphorylation. Conversely, dephosphorylation of this particular peptide is associated with complete activation. The protein phosphatase activity of the microsomal fraction may be separated into functionally and possibly also structurally different phosphorylase- and synthase-phosphatase activities, where the latter appears to be dependent on free cytoplasmic Ca2+. It is hypothesized that it is synthase-phosphatase activity that is absent in leukocytes from diabetic patients and is restored upon insulin treatment. |
