Glycogen storage disease type I Glycogen storage disease type I Glycogen storage disease type I (GSD I) or von Gierke disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase, and has an incidence in the American population of approximately 1 in 50,000 to 100,000 births. The deficiency impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis. Since these are the two principal metabolic mechanisms by which the liver supplies glucose to the rest of the body during periods of fasting, it causes severe hypoglycemia and results in increased
Glycogen phosphorylase Glycogen phosphorylase is regulated by both allosteric control and by phosphorylation. Hormones such as epinephrine, insulin and glucagon regulate glycogen phosphorylase using second messenger amplification systems that are linked to G proteins. Glucagon activates adenylate cyclase through a seven transmembrane receptor coupled to G which, in turn, activates adenylate cyclase to increase intracellular concentrations of cAMP. cAMP binds to and releases an active form of protein kinase A (PKA). Next, PKA phosphorylates phosphorylase kinase, which, in turn, phosphorylates glycogen phosphorylase b, transforming it into the active glycogen phosphorylase a. This phosphorylation is added onto the glycogen phosphorylase b serine 14.