6-phosphofructokinase, muscle type (PFKM)

6-phosphofructokinase, muscle type (PFKM) is an essential enzyme that catalyzes the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate using ATP, constituting the first committed and rate-limiting step in the glycolytic pathway[1][7]. It functions primarily as a tetrameric complex composed of muscle-type subunits in skeletal muscle, but is also expressed in heart, brain, and erythrocytes[1][2]. PFKM is crucial for the efficient breakdown of glycogen and the generation of ATP, especially in tissues with high-energy demand. Inherited deficiency causes glycogen storage disease type VII (Tarui disease), characterized by exercise-induced muscle cramps, weakness, myopathy, and in some cases hemolytic anemia[1][2]. Overexpression or dysregulation of PFKM has been implicated in metabolic disturbances such as type 2 diabetes and insulin resistance[1]. Recent research also identifies a novel nuclear function for PFKM as a protein kinase that phosphorylates histone H3 at serine 10, influencing mitosis and cell proliferation[3]. There are currently no clinically approved drugs specifically targeting PFKM, but general glycolysis inhibitors impact its function[1][2][7].

Other names

6-phosphofructo-1-kinasePFK-1PFK-APFK1PFKAPFKXphosphofructo-1-kinase isozyme Aphosphofructokinase 1phosphofructokinase, polypeptide Xphosphofructokinase-MphosphohexokinaseATP-dependent 6-phosphofructokinase, muscle type

Modulation of glycolytic flux (inhibition/activation adjusts cellular ATP production); Regulation of histone phosphorylation and mitotic progression (recent discovery)