Why is it important that hexokinase and phosphofructokinase-1 are not used in gluconeogenesis?
The correct answer and explanation is:
Hexokinase and phosphofructokinase-1 (PFK-1) are key enzymes in glycolysis, and their roles in gluconeogenesis must be carefully regulated to ensure the proper functioning of metabolic processes. These enzymes catalyze irreversible steps in glycolysis: hexokinase converts glucose to glucose-6-phosphate, and PFK-1 catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. Their participation in gluconeogenesis would mean reversing these reactions, which would be highly unfavorable energetically.
In gluconeogenesis, the synthesis of glucose from non-carbohydrate precursors like lactate, pyruvate, or amino acids occurs mainly in the liver and kidneys. For this process to proceed, cells must bypass the irreversible steps of glycolysis by using different enzymes. This is necessary to avoid wasting energy and resources in an attempt to reverse the glycolytic pathway. If hexokinase and PFK-1 were involved, the reactions would not only require excessive energy input, but they could also lead to the futile cycle of glucose being both consumed and synthesized simultaneously, thereby wasting ATP.
Instead of hexokinase, the enzyme glucose-6-phosphatase is used in gluconeogenesis to convert glucose-6-phosphate back to glucose. Similarly, instead of PFK-1, the enzyme fructose-1,6-bisphosphatase is involved in converting fructose-1,6-bisphosphate to fructose-6-phosphate. Both of these alternative enzymes work in the opposite direction of the glycolytic pathway and are regulated in a way that ensures gluconeogenesis can occur efficiently, using energy derived from other sources, such as fatty acid oxidation, rather than relying on the ATP-consuming steps of glycolysis.
This regulation allows the body to maintain glucose homeostasis and avoid energy inefficiency during metabolic transitions, particularly when glucose availability is low.