6-phosphofructokinase (Schistosoma) (PFK)

Schistosoma phosphofructokinase (PFK) is a pivotal regulatory enzyme in the glycolytic pathway of Schistosoma parasites, such as S. mansoni and S. japonicum, which cause schistosomiasis (UniProt P12858). Adult schistosomes are homolactic fermenters that rely almost exclusively on the high-rate conversion of glucose to lactate for energy production while inhabiting the host's bloodstream (Bueding & Mansour, 1957). PFK catalyzes the ATP-dependent phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, serving as a rate-limiting step in this essential metabolic process. Historically, trivalent antimonial drugs like antimony potassium tartrate were the mainstay of treatment, exerting their effect by selectively inhibiting schistosome PFK at concentrations that do not significantly affect the human host's enzyme (Mansour & Bueding, 1954). This inhibition leads to a rapid decrease in ATP levels, causing muscular paralysis and the eventual death of the parasite. Despite the clinical shift toward praziquantel, Schistosoma PFK remains a significant target for drug discovery due to the parasite's absolute metabolic dependence on glycolysis (PubMed 2121451).

Other names

Phosphofructokinase-1PFK-1ATP-dependent phosphofructokinasePhosphofructokinase

The primary mechanism involves the selective inhibition of the parasite's 6-phosphofructokinase enzyme, which halts the glycolytic flux necessary for ATP production in adult schistosomes (Bueding & Mansour, 1957). This metabolic blockade results in the loss of motor activity and detachment of the worms from the host's blood vessel walls.