Phosphofructokinase (PFK) exists in three isoforms in humans: muscle (PFKM), liver (PFKL), and platelet (PFKP). These isoforms function as subunits of the mammalian tetramer phosphofructokinase, with the tetramer composition varying depending on the tissue type . The muscle isoform, PFKM, is encoded by the PFKM gene and is predominantly expressed in skeletal muscle tissue .
PFKM is a homotetrameric enzyme, meaning it forms a tetramer composed of four identical subunits. The enzyme is allosterically regulated, meaning its activity can be modulated by various metabolites. For instance, ATP acts as an allosteric inhibitor, while AMP and fructose-2,6-bisphosphate serve as activators .
The primary function of PFKM is to catalyze the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, a key step in glycolysis. This reaction is essentially irreversible and serves as a major control point in the glycolytic pathway . By regulating this step, PFKM controls the rate of glucose metabolism and energy production in muscle cells.
PFKM’s activity is regulated by various allosteric effectors. High levels of ATP inhibit PFKM, reducing glycolysis when energy is abundant. Conversely, high levels of AMP and fructose-2,6-bisphosphate activate PFKM, enhancing glycolysis when energy is needed . This regulation ensures that glycolysis is tightly controlled in response to the cell’s energy status.
PFKM is subject to both allosteric regulation and covalent modification. Allosteric regulation involves the binding of metabolites like ATP, AMP, and fructose-2,6-bisphosphate to specific sites on the enzyme, altering its activity . Covalent modification, such as phosphorylation, can also modulate PFKM activity, although this is less common compared to allosteric regulation.