Volume I Glycogen: A Historical Overview, An Adjunct To Thesis Volume Ii Non-Glucose Components Of Glycogen

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Biochemistry and Molecular Biology

First Committee Member

William J. Whelan, Committee Chair


Investigations have been carried out on three non-glucose components of native glycogen: protein, glucosamine, and phosphate. The protein, glycogenin, appears to serve as the primer upon which new molecules of glycogen are synthesized. When cell extracts are incubated with ($\sp $C) UDPG, ($\sp $C) glucose becomes transferred onto pre-existing chains of alpha-1,4 linked glucose associated with free glycogenin. The transferase and glycogenin remain associated during various purification steps. Liver glycogen appears to contain less than 0.02% protein which may correspond to the presence of one molecule of glycogenin (37 kDa) per alpha particle of of liver glycogen. The "core beta particle" within each alpha particle may be synthesized upon glycogenin, while the remaining 20-40 beta particles may arise from each other.When an effort was made to radiolabel the protein in liver glycogen by reductive methylation, most of the radioactivity was incorporated into another component which we identified as glucosamine. Previous studies (Maley et al., 1966 a and b) had demonstrated that the administration of galactosamine to an animal resulted in the incorporation of glucosamine into liver glycogen. We now have demonstrated the natural occurrence of glucosamine in liver glycogen (but not muscle glycogen) from various species in an amount of about one molecule per molecule of glycogen. The glucosamine is underivatized, appears to be randomly scattered in the glycogen, and may be derived from dietary galactosamine. When we administered ($\sp $C) galactosamine and glucose intraperitoneally to a fasted rabbit, ($\sp $C) glucosamine became incorporated into kidney and liver glycogen, but not skeletal muscle or heart glycogen. Such liver glycogen could be fractionated on CM-cellulose into peaks postulated to represent (1) fasting glycogen, (2) glycogen derived from perivenous cells, and (3) glycogen from periportal cells.Similar to Fontana (1980), we observed that native liver glycogen could be fractionated on DEAE-cellulose apparently on the basis of phosphate content. The more strongly bound glycogen possessed a greater molecular weight and content of glucosamine and phosphate. Possible explanations for these subfractions are considered. The phosphate appears to be concentrated near the center of the glycogen molecules. About 30% appears to be associated with glucose-6P and the remainder with an unidentified phosphodiester. The phosphate may stimulate glycogen synthesis. How the phosphate becomes incorporated is unknown.


Biology, General

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