Which enzyme is primarily affected in McArdle disease, characterized by muscle cramping after exercise?

In McArdle disease, the primary issue lies with glycogen phosphorylase, which is an enzyme crucial in the glycogenolysis pathway. This enzyme is responsible for breaking down glycogen into glucose-1-phosphate, which is then converted into glucose for energy production, particularly during periods of exercise when muscle demand for energy increases.

Due to a deficiency or dysfunction of glycogen phosphorylase in individuals with McArdle disease, the muscles cannot effectively utilize glycogen stores during physical activity. This results in an inability to deliver adequate energy when needed, leading to symptoms such as muscle cramping, fatigue, and pain during exercise. Notably, individuals with this condition may experience a marked improvement in symptoms if they warm up slowly before exercising, as this can help stimulate alternative pathways to produce energy.

Other enzymes listed are associated with different metabolic disorders. Acid maltase is implicated in Pompe disease, a disorder affecting lysosomal glycogen degradation. The branching enzyme is involved in the synthesis of glycogen and is associated with Andersen disease. Pyruvate dehydrogenase is key in converting pyruvate to acetyl-CoA and is linked to various metabolic diseases but not specifically to glycogen metabolism deficiencies like McArdle disease.