ATP-dependent 6-phosphofructokinase, liver type

PFKL (ATP-dependent 6-phosphofructokinase, liver type) is a glycolytic enzyme that catalyzes the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate, a key regulatory step in glucose metabolism (UniProt: P17858). Beyond its canonical glycolytic role, PFKL also negatively regulates the phagocyte oxidative burst by controlling NADPH biosynthesis and reactive oxygen species production, linking metabolic and immune function.

PFKL is widely expressed and plays a central role in cellular energy metabolism. The protein coordinates the metabolic switch toward glycolysis in activated macrophages, balancing glucose utilization between the pentose phosphate pathway and glycolytic flux.

In Alzheimer's Disease, PFKL is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics; mean log2FC −0.281). This reduction in glycolytic capacity may reflect broader metabolic dysfunction in AD pathology, potentially contributing to neuronal energy deficit and impaired immune cell function in the diseased brain.