**Question:** McArdle's disease is due to deficiency of -

A. Lactate dehydrogenase (LDH)
B. Pyruvate kinase
C. Creatine kinase (CK)
D. Myophosphorylase

**Correct Answer:** **D. Myophosphorylase**

**Core Concept:** McArdle's disease (myopathic variant of congenital myasthenic syndrome) is a rare genetic disorder characterized by severe exercise intolerance, muscle pain, and cramps. It is caused by deficiency or dysfunction of myophosphorylase, an enzyme involved in glycogenolysis, the process of breaking down glycogen to produce glucose for energy during exercise.

**Why the Correct Answer is Right:** Myophosphorylase, also known as glycogen phosphorylase, is responsible for the initial step in glycogenolysis, specifically the breakdown of glycogen into glucose-1-phosphate. In McArdle's disease, this deficiency leads to impaired breakdown of glycogen during periods of intense exercise. As glycogen stores cannot be utilized for energy production, patients experience severe fatigue, muscle pain, and cramps during physical activity.

**Why Each Wrong Option is Incorrect:**

A. Lactate dehydrogenase (LDH) is involved in the conversion of lactate and pyruvate during cellular respiration, not in glycogenolysis. LDH deficiency would not cause the specific symptoms seen in McArdle's disease.

B. Pyruvate kinase is an enzyme involved in the last step of glycolysis and does not play a role in glycogenolysis. Its deficiency would not lead to the muscle symptoms seen in McArdle's disease.

C. Creatine kinase (CK) is an enzyme involved in the production of ATP from ADP during cellular respiration, specifically in the mitochondria. CK deficiency would not result in the specific symptoms of McArdle's disease.

**Clinical Pearl:** McArdle's disease primarily affects the skeletal muscles, leading to exercise intolerance, muscle pain, and cramps. This disorder serves as a reminder of the importance of understanding the correct enzymes and pathways involved in glycogenolysis and cellular respiration, particularly in relation to muscle function and exercise capacity.