During times of physiological stress, the adrenal medulla releases epinephrine to signal the body's need for blood glucose. The glucose is initially derived from hepatic glycogenolysis. Hepatocyte α1-adrenergic GPCR activation by epinephrine leads to a phospholipid-dependent cascade, causing Ca2+ to move from the endoplasmic reticulum (ER) to the cytoplasm. This results in the formation of a complex between Ca2+ and calmodulin (CaM), which then activates hepatic phosphorylase kinase b. Additionally, the released Ca2+ also aids in the activation of protein kinase C, which can phosphorylate and inactivate glycogen synthase a. 

Glycogen storage diseases (GSD) are a group of genetic disorders that arise from defects in enzymes necessary for glycogen degradation or, less commonly, glycogen synthesis. These diseases can lead to the formation of structurally abnormal glycogen or the accumulation of excessive amounts of normal glycogen in specific tissues due to impaired degradation. The defects can affect a single tissue, like the liver (causing hypoglycemia) or muscle (resulting in muscle weakness), or have a more generalized impact on various tissues, including the heart and kidneys. The severity of these diseases varies, ranging from fatal in early childhood to mild disorders that are not life-threatening. Figure 11.8 illustrates some of the more prevalent GSD. Notably, GSD II is the only lysosomal GSD since glycogen metabolism primarily occurs in the cytosol. 

In summary, the activation of liver phosphorylase kinase during physiologic stress involves the release of epinephrine, which stimulates hepatic glycogenolysis. This process is mediated by the binding of epinephrine to hepatocyte α1-adrenergic GPCR, resulting in the activation of a phospholipid-dependent cascade and the subsequent release of Ca2+ from the ER into the cytoplasm. The Ca2+ then forms a complex with CaM, which activates hepatic phosphorylase kinase b. Additionally, the released Ca2+ also activates protein kinase C, leading to the phosphorylation and inactivation of glycogen synthase a. Glycogen storage diseases are genetic disorders caused by defects in enzymes required for glycogen metabolism, resulting in abnormal glycogen structure or excessive glycogen accumulation in specific tissues. These diseases can affect various tissues and vary in severity, with GSD II being the only lysosomal GSD.
Liver phosphorylase kinase activation: During physiologic stress, epinephrine is released from the adrenal medulla and signals the need for blood glucose. This glucose initially comes from hepatic glycogenolysis. Binding of epinephrine to hepatocyte α1-adrenergic
GPCR activates a phospholipid-dependent cascade (see p. 205) that results in movement of Ca2+ from the ER into the cytoplasm. A Ca2+– CaM complex forms and activates hepatic phosphorylase kinase b. [Note: The released Ca2+ also helps to activate protein kinase C that can phosphorylate (therefore, inactivate) glycogen synthase a.]
VI. GLYCOGEN STORAGE DISEASES
GSD are a group of genetic diseases caused by defects in enzymes required for glycogen degradation or, more rarely, glycogen synthesis. They result either in formation of glycogen that has an abnormal structure or in the accumulation of excessive amounts of normal glycogen in specific tissues as a result of impaired degradation. A particular enzyme may be defective in a single tissue, such as the liver (resulting in hypoglycemia) or muscle (causing muscle weakness), or the defect may be more generalized, affecting a variety of tissues, such as the heart and kidneys. Severity ranges from fatal in early childhood to mild disorders that are not life threatening. Some of the more prevalent GSD are illustrated in Figure 11.8. [Note: Only GSD II is lysosomal because glycogen metabolism occurs primarily in the cytosol.]
VII. CHAPTER SUMMARY