Regulation of Glycolysis and Gluconeogenesis: The Role of Bifunctional Enzyme PFK2/FBPase-2

An enzyme with two different, often opposing, catalytic activities on one polypeptide chain. For instance, phosphofructokinase 2 synthesizes fructose 2,6-bisphosphate and fructose 2,6-bisphosphatase hydrolyzes it, yet both active sites are on the same polypeptide chain.

The enzyme we are referring to is commonly known as bifunctional enzyme

The enzyme we are referring to is commonly known as bifunctional enzyme. Bifunctional enzymes possess two distinct catalytic activities on the same polypeptide chain. In the case of phosphofructokinase 2/fructose 2,6-bisphosphatase, it is involved in the regulation of glycolysis and gluconeogenesis, which are two opposing metabolic pathways.

Phosphofructokinase 2 (PFK2) is responsible for synthesizing fructose 2,6-bisphosphate, an allosteric activator of the glycolytic enzyme, phosphofructokinase 1 (PFK1). Fructose 2,6-bisphosphate stimulates the activity of PFK1, ultimately increasing the rate of glycolysis. PFK2, through its kinase activity, adds a phosphate group to fructose 6-phosphate, producing fructose 2,6-bisphosphate.

On the other hand, fructose 2,6-bisphosphatase (FBPase-2) hydrolyzes fructose 2,6-bisphosphate, converting it back to fructose 6-phosphate. This reaction is an important step in the regulation of gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate carbon sources. FBPase-2, through its phosphatase activity, removes a phosphate group from fructose 2,6-bisphosphate.

Both the kinase and phosphatase activities of PFK2/FBPase-2 are catalyzed by distinct active sites on the same polypeptide chain. The enzyme can switch between its kinase and phosphatase activities depending on the metabolic needs of the cell. Several factors, such as hormones and metabolites, regulate the interconversion between fructose 2,6-bisphosphate synthesis and hydrolysis, maintaining the balance between glycolysis and gluconeogenesis.

The presence of a bifunctional enzyme like PFK2/FBPase-2 allows for efficient coordination of metabolic processes. By having both activities on a single polypeptide chain, the enzyme can rapidly respond to changes in intracellular conditions and fine-tune the rates of glycolysis and gluconeogenesis. This kind of regulatory mechanism is crucial for maintaining energy homeostasis in the cell.

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