Glycogen defect

Eleven defects in the metabolism of glycogen have been reported nine of them affect skeletal muscle directly (see Figure 5), but only glycogenosis type II (acid maltase deficiency) and glycogenesis type V (myophosphorylase deficiency) are reasonably common the rest are rare and some have been recorded in isolated case studies only. 

Figure 5. Glycogen metabolism and glycolysis. Dotted lines indicate sites of metabolic defects involving enzymes l-XI.

Phosphorylase deficiency (McArdle s disease, glycogenosis type V) is an autosomal recessive myopathy caused by a genetic defect of the muscle isoenzyme of glycogen phosphorylase (Fig. 42-1). Intolerance of strenuous exercise is present from childhood, but usually onset is in adolescence, with cramps after exercise [1, 5]. Myoglobinuria occurs in about one-half of patients. If they avoid intense exercise, most patients can live normal lives however, about one-third of them develop some degree of fixed weakness, usually as a late-onset manifestation of the disease. In a few patients, weakness rather than exercise-related cramps and myoglobinuria characterizes the clinical picture. 

Glycogen metabolism disorders Amylo-l,6-glucosidase defect Liver phosphorylase defect Glycogen synthetase defect... 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

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... 

Metabolic Effects of Mutant Enzymes Predict and explain the effect on glycogen metabolism of each of the following defects caused by mutation (a) loss of the cAMP-binding site on the regulatory subunit of protein kinase A (PKA) (b) loss of the protein phosphatase inhibitor (inhibitor 1 in Fig. 15-40) (c) overexpression of phosphorylase b kinase in liver (d) defective glucagon receptors in liver. 

This is a group of recessive genetic disorders resulting in defects in glycogen synthesis or breakdown, with each type (and there are several)... 

---