Glycogen synthesis in the astrocyte: from glycogenin to proglycogen to glycogen

Abstract

The astrocyte of the newborn rat brain has proven to be a versatile system 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 observations 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 starved of glucose, free glycogenin is present. 2) When these astrocytes are fed with glucose, proglycogen is synthesized from the glycogenin primer by a glycogen-synthase-like UDPglucose transglucosylase activity (proglycogen synthase) distinct from the well-recognized glycogen synthase, and synthesis stops at this point. 3) Proglycogen is the precursor of macromolecular glycogen, which is synthesized from proglycogen by glycogen synthase when glucose is fed to untreated astrocytes, accounting for the much greater accumulation of total glycogen. 4) The stimulus to proglycogen and macroglycogen synthesis that occurs on feeding glucose to untreated or ammonia-treated astrocytes is the result of the activation of proglycogen synthase, not of glycogen synthase. 5) Therefore, in the synthesis of macromolecular glycogen from glycogenin via proglycogen, the step between glycogenin and proglycogen is rate-limiting. 6) The discovery of additional potential control points in glycogen synthesis, now emerging, may assist the identification of so-far-unexplained aberrations of glycogen metabolism.

Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter

“…It is not surprising that nerve glycogen content remained at a low plateau level after 30 min of glucose withdrawal rather than falling to zero. Cultured astrocytes are not able to mobilize their glycogen stores completely in the absence of glucose (Lomako et al, 1993(Lomako et al, , 1995. Glycogen is composed of a protein core, glycogenin, with many attached glucose residues.…”

Effect of Cooking Condition on the Water-Soluble Flavor Precursors in Various Beef Muscles from Hanwoo (Korean Cattle)

“…The glycogen in animal muscles is classified into two types, i.e., macroglycogen and proglycogen (Lomako et al, 1991(Lomako et al, , 1993. The macroglycogen (MW: 10,000 kDa) is found in muscles at a high proportion to protein (about 0.4%) and easily dissolves in acid solution.…”

New and specific nucleoside diphosphate glucose substrates for glycogenin

“…When working with tissue extracts or partly purified preparations containing both glycogenin and synthase, it has been possible to distinguish between the two enzymes by virtue of the fact that the Km values of glycogenin and synthase for UDP-glucose differ by three orders of magnitude [2M], although the form of synthase we have named proglycogen synthase is active at the same micromolar UDP-glucose concentration as is optimal for glycogenin [5]. Another distinction is possible because glycogenin is activated by Mn 2+, while the synthases are activated by glucose 6P, and not vice versa [6][7][8].…”