Plasmodium falciparum L-lactate dehydrogenase (PfLDH)

Plasmodium falciparum L-lactate dehydrogenase (PfLDH) is a vital enzyme in the anaerobic glycolytic pathway of the malaria parasite, which lacks a functional citric acid cycle during its blood stage and depends entirely on glycolysis for energy (Source: 1.3.3, 1.3.5). The enzyme catalyzes the reversible conversion of pyruvate to lactate, a process essential for regenerating NAD+ and maintaining the high glycolytic flux required for parasite survival (Source: 1.2.3, 1.3.5). PfLDH is structurally distinct from human LDH isoforms, notably possessing a unique five-amino acid insertion in its substrate-specificity loop, which makes it an attractive target for selective antimalarial drug development (Source: 1.2.3, 1.3.3). Several drugs, including chloroquine and repurposed agents like posaconazole, have been shown to interact with the enzyme's NADH binding pocket (Source: 1.3.2, 1.3.4). Beyond its role as a therapeutic target, PfLDH serves as a critical diagnostic biomarker in rapid diagnostic tests (RDTs) used to detect and monitor malaria infections globally (Source: 1.1.1, 1.1.5). Targeting this enzyme offers a strategy to combat drug-resistant malaria by disrupting the parasite's primary energy production mechanism (Source: 1.3.1, 1.3.3).

Other names

pLDHLDH-PParasite lactate dehydrogenaseL-lactate dehydrogenase

Inhibition of PfLDH typically involves competitive binding at the NADH cofactor site or the substrate binding pocket, which prevents the conversion of pyruvate to lactate. This disruption halts the regeneration of NAD+, leading to the cessation of anaerobic glycolysis and a subsequent depletion of ATP, ultimately resulting in parasite death (Source: 1.3.3, 1.3.5).