Glycogen-storage site

FIGURE 15.15 (a) The structure of a glycogen phosphorylase monomer, showing the locations of the catalytic site, the PLP cofactor site, the allosteric effector site, the glycogen storage site, the tower helix (residnes 262 throngh 278), and the snbnnit interface. 

Inhibitor site, which binds caffeine and related molecules Glycogen storage site... 

The 357-residue mammalian glucose-6-phospha-tase plays an important role in metabolism (Chapter 17). Defects in the enzyme cause a glycogen storage disease (Box 20-D) and severe disruption of metabolism.731 However, the molecular basis of its action is not well-known. Furthermore, the active site of the enzyme is located in the lumen of the endoplasmic reticulum732 and glucose-6-phosphate must pass in through the plasma membrane. An additional glucose-6-phosphate transporter subunit may be required to allow the substrate to leave the cytoplasm.73... 

Because the liver is a major processor of dietary and endogenous carbohydrates, liver disease affects carbohydrate metabolism in a variety of ways (see Chapter 25). However, none of the conventional modes of evaluating carbohydrate metabolism have value in the diagnosis of liver disease. Because the liver is the major site of both glycogen storage and gluconeogenesis, hypoglycemia is a common complication in certain liver diseases, particularly Reye s syndrome, fulminant hepatic failure, advanced cirrhosis, and hepatocellular carcinoma. 

The debranching enzyme has two enzymatic activities a glycosyltransferase and an a-1,6 gly-cosidase activity. There are two forms of deb-rancher enzyme deficiency in glycogen storage disease type Ilia (85 % of patients), the enzyme is deficient in both liver and muscle, whereas in glycogen storage disease type nib (15 % of patients), the enzyme is only deficient in liver but is normal in muscle. The preservation of muscle enzyme activity is caused by mutations in exon 3 where a muscle promoter allows translational start using a secondary start site after the mutation. Isolated deficiency of only one of the two enzyme activities is very rare. 

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