Phosphofructokinase Regulation



Phosphofructokinase (PFK) is an important enzyme in virtually all living cells. It performs the committed step in the glycolytic pathway, namely, the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. Glycolysis is a pathway that uses glucose to maintain a steady amount of ATP, the major energy carrier in living cells.

Phosphofructokinase is a multisubunit protein. In such proteins, the subunits may behave cooperatively; that is, the activity of one subunit influences the activity of all the other subunits. Proteins that exhibit this behavior are known as allosteric proteins. An especially notable example of an allosteric protein is hemoglobin, which is an oxygen-transport protein rather than an enzyme.

The activity of an allosteric enzyme such as PFK can be regulated by the binding of a small molecule that acts as an activator or inhibitor. Because the subunits act cooperatively, activation of one subunit leads to activation of all the subunits, and inhibition of one subunit leads to inhibition of all the subunits. We will examine PFK as a model for understanding allosteric enzyme regulation.

Learning objectives

  • Understand the regulation of phosphofructokinase at a structural level.
  • Gain insight into cooperative allosteric enzyme regulation.