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Pride and prejudice: The discovery of the primer for glycogen synthesis

The study of glycogen and its metabolism has been important for the progress of biochemistry as a whole because of the number of general concepts that have emerged therefrom. It was the first macromolecule to be synthesized in vitro by Carl and Gerty Cori. Its synthesis from UDPglucose by glycogen synthase was one of the crowning achievements of Luis Leloir, who discovered the nucleoside diphosphate sugars. Cyclic AMP and the second-messenger concept arose out of a study of the breakdown of liver glycogen. Protein phosphorylation and dephosphorylation, as a means of regulating enzyme activity, were discovered out of the realization that active muscle phosphorylase is a phosphorylated form of the inactive, unphosphorylated enzyme. Arising from the discovery of how glycogen can be synthesized with phosphorylase and branching enzyme came the realization that a primer is necessary for this synthesis to take place. The primer can be glycogen itself. Originally it was thought that the