What is the primary metabolic deficiency in McArdle's disease?

McArdle's disease is fundamentally caused by a deficiency in the enzyme muscle glycogen phosphorylase. This enzyme plays a crucial role in the breakdown of glycogen, which serves as a stored form of glucose within muscle tissues. When muscle glycogen phosphorylase is deficient, the muscles are unable to properly utilize glycogen for energy, particularly during periods of exertion. This leads to a phenomenon known as 'exercise intolerance' or muscle cramps after exertion, as there is an inadequate supply of glucose for muscle metabolism.

Individuals with McArdle's disease exhibit characteristic signs such as muscle pain and fatigue after exercise, which stem from their inability to mobilize glycogen stores. The accumulation of glycogen in muscle tissues occurs because it cannot be broken down efficiently into glucose.

In contrast, hexokinase is involved in the initial phosphorylation of glucose, glucose-6-phosphate dehydrogenase is critical for the pentose phosphate pathway (important for generating NADPH), and phosphofructokinase is a key regulator of glycolysis. While these enzymes play essential roles in metabolism, they are not the primary defect in McArdle's disease. Thus, the identification of muscle glycogen phosphorylase as the primary metabolic