GLYCOGEN-SYNTHESIS IN THE ASTROCYTE - FROM GLYCOGENIN TO PROGLYCOGEN TO GLYCOGEN

The astrocyte of the newborn rat brain has proven to be a versatile sy stem in which to study glycogen biogenesis. We have taken advantage of the rapid stimulation of glycogen synthesis that occurs when glucose is fed to astrocytes, and the marked limitation on this synthesis that occurs in astrocytes previously exposed to ammonium ions. These obser vations have been related to our earlier reports of the initiation of glycogen synthesis on a protein primer, glycogenin, and the discovery of a low-molecular-weight form of glycogen, proglycogen. The following conclusions have been drawn: 1) In the ammonia-treated astrocytes sta rved of glucose, free glycogenin is present. 2) When these astrocytes are fed with glucose, proglycogen is synthesized from the glycogenin p rimer by a glycogen-synthase-like UDPglucose transglucosylase activity (proglycogen synthase) distinct from the well-recognized glycogen syn thase, and synthesis stops at this point. 3) Proglycogen is the precur sor of macromolecular glycogen, which is synthesized from proglycogen by glycogen synthase when glucose is fed to untreated astrocytes, acco unting for the much greater accumulation of total glycogen. 4) The sti mulus to proglycogen and macroglycogen synthesis that occurs on feedin g glucose to untreated or ammonia-treated astrocytes is the result of the activation of proglycogen synthase, not of glycogen synthase. 5) T herefore, in the synthesis of macromolecular glycogen from glycogenin via proglycogen, the step between glycogenin and proglycogen is rate-l imiting. 6) The discovery of additional potential control points in gl ycogen synthesis, now emerging, may assist the identification of so-fa r-unexplained aberrations of glycogen metabolism.