6-phosphofructokinase (PFK-1)

6-phosphofructokinase (PFK-1) is a critical, rate-limiting enzyme in the glycolytic pathway that catalyzes the conversion of fructose-6-phosphate and ATP to fructose-1,6-bisphosphate and ADP [StatPearls]. In humans, the enzyme exists as a tetramer composed of three distinct subunits—muscle (PFKM), liver (PFKL), and platelet (PFKP)—which are expressed in various combinations across different tissues to meet specific metabolic demands [UniProt]. PFK-1 serves as a major metabolic sensor, highly regulated by allosteric activators like fructose-2,6-bisphosphate and AMP, and inhibitors such as ATP and citrate, ensuring that glycolytic flux matches the cell's energy status [PubMed]. In oncology, PFK-1 (particularly the PFKP isoform) is frequently overexpressed to facilitate the Warburg effect, supporting the high energy and biosynthetic requirements of rapidly proliferating tumor cells [PubMed]. Conversely, genetic mutations in the PFKM gene lead to Tarui disease, a metabolic disorder characterized by exercise intolerance, myogenic hyperuricemia, and compensated hemolysis [NIH]. While PFK-1 is an attractive target for metabolic reprogramming in cancer, its fundamental role in systemic glucose homeostasis and red blood cell function presents significant therapeutic challenges regarding safety and off-target effects [PubMed].

Other names

Phosphofructokinase-1PFK16-phosphofructo-1-kinasePhosphofructokinase, muscle type (PFKM)Phosphofructokinase, liver type (PFKL)Phosphofructokinase, platelet type (PFKP)Fructose-6-phosphate kinase

Catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate using ATP as the phosphate donor, serving as the primary rate-limiting and committed step of glycolysis [StatPearls].