## **Core Concept**
The question revolves around the regulation of gluconeogenesis, specifically focusing on the enzyme fructose 1,6-bisphosphatase and its interaction with fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate is a potent regulator of gluconeogenesis and glycolysis, acting as an inhibitor of fructose 1,6-bisphosphatase (a key gluconeogenic enzyme) and an activator of phosphofructokinase-1 (a key glycolytic enzyme).

## **Why the Correct Answer is Right**
In the disorder described, fructose 1,6-bisphosphatase becomes less sensitive to inhibition by fructose 2,6-bisphosphate. This means that gluconeogenesis would be less inhibited, leading to an increase in glucose production by the liver. The expected metabolic changes would include increased gluconeogenesis, increased glucose levels, and potentially decreased glycolysis due to the reduced inhibitory effect on gluconeogenic pathways.

## **Why Each Wrong Option is Incorrect**
- **Option A:** This option would likely be increased due to the enhanced gluconeogenic flux as a result of decreased inhibition of fructose 1,6-bisphosphatase by fructose 2,6-bisphosphate.
- **Option B:** This might be decreased because the reduced sensitivity to fructose 2,6-bisphosphate would favor gluconeogenesis over glycolysis, potentially lowering pyruvate conversion to glucose through glycolysis.
- **Option C:** This would likely be increased as gluconeogenesis produces glucose-6-phosphate, which can then be converted to glucose by glucose-6-phosphatase.
- **Option D:** This option suggests a decrease in a metabolite that is directly related to glycolytic activity. If glycolysis is decreased due to the shift towards gluconeogenesis, one might expect changes in metabolites associated with glycolysis.

## **Clinical Pearl / High-Yield Fact**
A key point to remember is that fructose 2,6-bisphosphate plays a critical role in the regulation of glucose metabolism, acting as a signal of high energy status and promoting glycolysis while inhibiting gluconeogenesis. Disorders affecting the regulation of gluconeogenic enzymes by fructose 2,6-bisphosphate can lead to disturbances in glucose homeostasis.

## **Correct Answer:** D.