Fructose-bisphosphate aldolase (FBPA) (FBPA)

Fructose-bisphosphate aldolase (FBPA) is a key enzyme in the glycolytic pathway, catalyzing the reversible conversion of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate (UniProt: P14223). In protozoan parasites such as Plasmodium falciparum, Trypanosoma, and Leishmania, this enzyme is essential for energy production, as these organisms rely heavily on glycolysis for ATP during their infectious stages (PMID: 15103319). Beyond its metabolic role, protozoan aldolase often exhibits moonlighting functions, particularly in Apicomplexan parasites where it bridges the actin-myosin motor to surface adhesins, a process vital for host cell invasion (PMID: 18466493). This dual functionality makes FBPA an attractive therapeutic target, as inhibitors can potentially block both parasite metabolism and infection mechanisms. While humans also utilize Class I aldolases, structural differences in the parasite enzyme—such as unique C-terminal sequences and distinct binding sites for adhesins—allow for the development of selective inhibitors (PMID: 25663143). Furthermore, the presence of the aldolase protein in the bloodstream of infected hosts serves as a diagnostic biomarker, utilized in various rapid diagnostic tests for malaria. Consequently, targeting and monitoring protozoan aldolase provides a multi-faceted approach to managing parasitic diseases.

Other names

AldolaseFructose-1,6-bisphosphate aldolaseD-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyaseFBA

Inhibition of the catalytic cleavage of fructose-1,6-bisphosphate to disrupt ATP production and disruption of the actin-aldolase-adhesin complex to prevent host cell invasion.