foszfofruktokináz1

Foszfofruktokináz1 (PFK1) is a key regulatory enzyme in glycolysis that catalyzes the phosphorylation of fructose‑6‑phosphate to fructose‑1,6‑bisphosphate. The human gene encoding this enzyme is located on chromosome 15q26, and it produces a heterogeneous protein composed of three identical subunits that can associate with regulatory subunits of other isoforms. In mammals, distinct tissue‑specific isoforms of PFK1 exist, including PFKL (liver type), PFKM (muscle type) and PFKP (platelet type). The foszfofruktokináz1 gene product is largely expressed in liver and other highly glycolytic tissues, where it responds to allosteric effectors such as fructose‑2,6‑bisphosphate, AMP, and citrate, thereby modulating the rate of glucose utilization.

The enzyme plays a crucial role in cellular energy metabolism, serving as a rate‑limiting step in glycolysis. Regulation of foszfofruktokináz1 activity affects metabolic flux toward lactate in anaerobic conditions and influences flux into the pentose phosphate pathway under oxidative stress. Genetic variations in the PFK1 locus have been linked to metabolic disorders, including hypoglycemia and certain myopathies. Mutations that reduce enzyme activity can impair lactate production and lead to fatigue during exercise, while overactivity has been associated with tumor progression, as many cancers exploit glycolytic intermediates for rapid proliferation and biosynthetic needs. Current research investigates small‑molecule modulators of PFK1 as potential therapeutic agents for metabolic diseases and cancer. Studies also examine the impact of post‑translational modifications, such as phosphorylation and glycosylation, on enzyme stability and activity. Thus, foszfofruktokináz1 remains a central focus in understanding energy metabolism and its dysregulation in disease.