fosfofruktokinase

Fosfofruktokinase, best known as phosphofructokinase-1 (PFK-1), is a cytosolic enzyme that catalyzes the ATP-dependent phosphorylation of fructose‑6‑phosphate to fructose‑1,6‑bisphosphate, a key committed step in glycolysis. This reaction uses magnesium as a cofactor and helps regulate the rate of glucose breakdown for energy production.

In humans, PFK-1 exists as tetramers formed from three catalytic subunit genes—PFKM (muscle), PFKL (liver), and PFKP (platelet/erythrocyte)—which generate tissue-specific isoforms. The enzyme is regulated primarily by allosteric effectors rather than by substrate concentration alone, allowing it to respond to cellular energy needs.

Allosteric regulation involves ATP, which inhibits PFK-1 when energy is abundant, and AMP or ADP, which relieve inhibition and activate the enzyme. Fructose‑2,6‑bisphosphate (F2,6BP) is a potent activator of PFK‑1. Citrate inhibits PFK‑1, signaling a sufficient supply of biosynthetic precursors. In liver and some other tissues, hormonal control modulates glycolysis through bifunctional enzymes called PFK-2/FBPase-2, which synthesize or degrade F2,6BP in response to insulin and glucagon, thereby adjusting PFK‑1 activity.

Physiologically, PFK‑1 helps synchronize carbohydrate utilization with cellular energy status and biosynthetic demands. Defects in PFK subunits can cause glycogen storage diseases, such as Tarui disease (PFKM deficiency) affecting muscle, or related hematologic issues from RBC PFK deficiencies. In cancer metabolism, increased PFK‑1 activity can support high glycolytic flux characteristic of the Warburg effect.