Glycogen Breakdown and Synthesis

Besides his investigations on glycogen, Bernard was concerned with the differences in carbohydrate metabolism between carnivores and herbivores. In the course of these studies he examined the role of the pancreas in digestion and its ability to hydrolyze starch and fats. For his work on the pancreas Bernard was made a Chevalier of the Legion of Honour, the citation stating that the award was for excellent work on the musical [vice medical ] properties of the pancreas (Leicester, 1974). 

In a book published in 1878, the year after his death, Bernard first enunciated the concept of homeostasis—a term coined much later (in 

Studies on the breakdown and synthesis of glycogen are particularly associated with the work of Carl and Gerti Cori in the 1930s and 1940s. They emigrated to the U.S. from Vienna in 1922 initially to Buffalo, N. Y. and later moved to Washington University School of Medicine at St. Louis in 1931, when they worked together on carbohydrate metabolism, work for which they received a Nobel prize in 1947. 

Phosphoglucomutase was isolated by the Coris and crystallized by Najjar. Its mechanism of action was suggested from experiments by Leloir in 1951 using [32P]. The enzyme is a phosphoprotein. Leloir showed that the phosphate group was transferred from the enzyme to G-1-P in the course of the reaction to give G-1,6 diP, which then donated the phosphate from its 1-position back to the enzyme, releasing G-6-P  

Phosphorylase was studied in depth. The enzyme from muscle was different from that catalyzing the same reaction in liver. Muscle phosphorylase but not that from liver, was activated by AMP, an early example of enzyme regulation by a ligand which was not a substrate. [Allosteric regulation was not postulated until the work of Jacob and 

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The glycolytic pathway and those for glycogen breakdown and synthesis are shown in Appendix 2. 

Glycogen breakdown and synthesis is regnlated by multiple second messengers indnced by neural or hormonal stimulation (see Figure 15-6). 

Glucagon stimulates glycogen breakdown and simultaneously inhibits glycogen synthesis in the liver. 

A variety of hormones affect the body s carbohydrate metabolism some increase carbohydrate reserves by promoting the synthesis of glycogen, others accelerate the rate of glycogen breakdown and glucose oxidation. Between them, they add formidable weapons to the cell s already powerful armoury of glucose control systems. 

This depends on the target of the activated PK-A for example, PK-A phosphorylates enzymes that are involved in glycogen metabolism, thus promoting glycogen breakdown and inhibiting glycogen synthesis in the short term. 

Several metabolic blocks [57] cause glycogen to accumulate in parenchyma or muscle some blocks affect glycogen breakdown and others affect glycogen synthesis. The absence of glucose-6-phosphatase, or von Gierke s disease, will be used as a model for all forms of glycogen storage disease. The other types will be mentioned only briefly. 

A good illustration of the regulatory properties of cAMP occurs in liver stimulated by glucagon. cAMP activates a protein kinase which phosphorylates both phosphorylase and glycogen synthetase, but while phosphorylase is activated, glycogen synthetase is inhibited by the phosphorylation. Consequently, cAMP at the same time stimulates glycogen breakdown and inhibits glycogen synthesis. 

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