Glycogen phosphorylase V, McArdle's Disease). More than 65 mutations in the PYGM gene that lead to McArdle disease have been identified to date. Symptoms of McArdle disease include muscle weakness, myalgia, and lack of endurance, all stemming from low glucose levels in muscle tissue. Mutations in the liver isoform of glycogen phosphorylase (PYGL) are associated with Hers' Disease (glycogen storage disease type VI). Hers' disease is often associated with mild symptoms normally limited to hypoglycemia, and is sometimes difficult to diagnose due to residual enzyme activity. The brain isoform of glycogen phosphorylase (PYGB) has been proposed as a biomarker for gastric cancer.
Glycogen is referred to as "hitting the wall". Glycogen depletion can be forestalled in three possible ways. First, during exercise, carbohydrates with the highest possible rate of conversion to blood glucose (high glycemic index) are ingested continuously. The best possible outcome of this strategy replaces about 35% of glucose consumed at heart rates above about 80% of maximum. Second, through endurance training adaptations and specialized regimens (e.g. fasting low-intensity endurance training), the body can condition type I muscle fibers to improve both fuel use efficiency and workload capacity to increase the percentage of fatty acids used as fuel, sparing carbohydrate use