**Core Concept**
Fructose 1,6-bisphosphatase is a key enzyme in gluconeogenesis, regulating the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate. It is primarily inhibited by fructose 2,6-bisphosphate, which is a potent allosteric inhibitor. A genetic disorder affecting the sensitivity of fructose 1,6-bisphosphatase to fructose 2,6-bisphosphate would disrupt normal gluconeogenic regulation.
**Why the Correct Answer is Right**
The lack of sensitivity to fructose 2,6-bisphosphate would lead to an increased activity of fructose 1,6-bisphosphatase. This would result in an increased conversion of fructose 1,6-bisphosphate to fructose 6-phosphate, thereby promoting gluconeogenesis. As a result, the metabolic changes observed in this disorder would include:
* Increased glucose production in the liver
* Elevated levels of glucose in the blood
* Increased activity of gluconeogenic enzymes
* Reduced activity of glycolytic enzymes
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because increased glucose production and elevated blood glucose levels are expected outcomes of the disorder. This is a consequence of the increased activity of fructose 1,6-bisphosphatase.
**Option B:** This option is incorrect because the disorder would actually lead to increased gluconeogenic activity, not decreased. The increased activity of fructose 1,6-bisphosphatase promotes gluconeogenesis, which is the opposite of what is stated in this option.
**Option C:** This option is incorrect because the disorder would lead to increased glucose production and elevated blood glucose levels, not decreased. The increased activity of fructose 1,6-bisphosphatase promotes gluconeogenesis, resulting in increased glucose production.
**Clinical Pearl / High-Yield Fact**
Fructose 1,6-bisphosphatase is a key regulatory enzyme in gluconeogenesis, and its activity is tightly controlled by fructose 2,6-bisphosphate. A genetic disorder affecting the sensitivity of fructose 1,6-bisphosphatase to fructose 2,6-bisphosphate can lead to significant metabolic disturbances, including hyperglycemia and increased glucose production.
**Correct Answer:** D
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