What is the site of dysfunction in glycogen storage disease, type I?

In glycogen storage disease type I (also known as von Gierke disease), the site of dysfunction is primarily in the endoplasmic reticulum. This condition is caused by a deficiency in the enzyme glucose-6-phosphatase, which is located in the lumen of the endoplasmic reticulum. This enzyme is crucial for the final step in gluconeogenesis and glycogenolysis, where glucose-6-phosphate is converted to free glucose.

When this enzyme is deficient, there is an accumulation of glycogen and glucose-6-phosphate in the liver and kidneys. This leads to symptoms such as hypoglycemia, hepatomegaly, and hyperlipidemia due to the disrupted ability to maintain normal blood sugar levels following fasting.

The endoplasmic reticulum's role is essential since it serves as a site for various biosynthetic processes, and in this specific condition, the failure to properly convert glucose-6-phosphate to glucose directly affects the organism's metabolism, leading to the symptoms associated with the disease. Understanding the function and dysfunction of the endoplasmic reticulum in this context highlights its critical role in cellular metabolism and energy regulation.