Regulation of renal glycogen synthase interconversion of two forms in vitro

Glycogen synthase (UDP glucose: glycogen α-4-glucosyltransferase, EC 2.4. 1.11) from rat kidney was stimulated 4- to 5-fold by glucose 6-phosphate. The for glucose 6-phosphate stimulation was about 0.45 mM. Glycogen synthase was not evenly distributed throughout the kidney. Total synthase activity was greatest in the outer cortex and cortico-medullary junction and least in the inner medulla. Glucose 6-phosphate stimulation was greatest in the outer cortex and least in the inner medulla. Glycogen synthase in crude homogenates was not complexed with glycogen and eluted from Sepharose 6-B with an apparent molecular weight of about 390 000.Renal glycogen synthase appeared to exist in two interconvertible forms, synthase I (activity in the absence of glucose 6-phosphate) and synthase D (requires glucose 6-phosphate for activity). The conversion of synthase D to I (synthase D phosphatase) was inhibited by F⁻, glycogen, ATP, Mn²⁺, and Co²⁺. The conversion was not altered by mercaptoethanol, AMP, Mg²⁺, or Ca²⁺. The conversion of synthase I to D (synthase I kinase) required ATP-Mg and was stimulated by cyclic AMP.It was suggested that the interconversion of renal glycogen synthase involved a phosphorylation-dephosphorylation. The significance of glycogen synthase interconversion to the regulation of renal glycogen synthesis is discussed.