What are the regulatory steps in glycolysis?

The regulatory steps in glycolysis are the reactions catalysed by hexokinase, phosphofructokinase, and pyruvate kinase.

Glycolysis is a metabolic pathway that breaks down glucose to produce energy in the form of ATP. It is regulated at three key enzymatic steps to ensure efficient energy production and to prevent wasteful overproduction of end products. These steps are catalysed by the enzymes hexokinase, phosphofructokinase, and pyruvate kinase.

The first regulatory step in glycolysis is the phosphorylation of glucose by hexokinase. This step is irreversible and commits the glucose molecule to the glycolytic pathway. Hexokinase is inhibited by its product, glucose-6-phosphate, in a classic example of feedback inhibition. This ensures that glucose is not unnecessarily committed to glycolysis when there is already a sufficient supply of glucose-6-phosphate.

The second regulatory step is the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate by phosphofructokinase. This is the most important regulatory step in glycolysis, as it is both irreversible and highly exergonic, meaning it releases a large amount of energy. Phosphofructokinase is allosterically inhibited by ATP and citrate, indicating a high energy status of the cell, and activated by AMP, indicating a low energy status. This ensures that glycolysis is upregulated when energy is needed and downregulated when it is not.

The final regulatory step is the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase. This step is also irreversible and exergonic, releasing a large amount of energy. Pyruvate kinase is inhibited by ATP and alanine and activated by fructose-1,6-bisphosphate. This ensures that glycolysis is downregulated when there is a high energy status and upregulated when there is a low energy status.

In summary, the regulation of glycolysis at the steps catalysed by hexokinase, phosphofructokinase, and pyruvate kinase ensures that energy production is closely matched to the needs of the cell. This is achieved through a combination of feedback inhibition and allosteric regulation, which respond to the energy status of the cell and the availability of substrates.