Tarui disease is due to deficiency of which enzyme?

• A. Phosphofructokinase
• B. Glycogen phosphorylase
• C. Debranching enzyme
• D. Glucose-6-phosphatase

Answer: (A)

Tarui disease is caused by a deficiency of the muscle form of phosphofructokinase-1, the enzyme that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis. This step is a major control point and essentially drives glycolysis forward; when it’s defective, skeletal muscle cannot efficiently break down glucose to generate ATP during exercise. The result is exercise intolerance with cramps and often myoglobinuria, because the muscle runs short of readily available energy and relies more on other, less efficient pathways. Moreover, because glycolysis is impaired, lactate levels fail to rise normally with activity, reflecting the bottleneck early in the pathway. Tarui disease is known as glycogen storage disease type VII, highlighting the glycogen-related muscle energy issue.

The other enzymes listed map to different glycogen storage diseases: deficiency of muscle glycogen phosphorylase causes McArdle disease, with poor exercise-induced lactate rise and muscle cramps; deficiency of debranching enzyme causes Cori disease, featuring abnormal glycogen with limit dextrin-like structures and fasting hypoglycemia; deficiency of glucose-6-phosphatase causes von Gierke disease, marked by severe hypoglycemia and hepatomegaly.