Enzymatic properties of the lactate dehydrogenase enzyme from Plasmodium falciparum

The lactate dehydrogenase enzyme from Plasmodium falciparum ( Pf LDH) is a target for antimalarial compounds owing to structural and functional differences from the human isozymes. The plasmodial enzyme possesses a five‐residue insertion in the substrate‐specificity loop and exhibits less marked substrate inhibition than its mammalian counterparts. Here we provide a comprehensive kinetic analysis of the enzyme by steady‐state and transient kinetic methods. The mechanism deduced by product inhibition studies proves that Pf LDH shares a common mechanism with the human LDHs, that of an ordered sequential bireactant system with coenzyme binding first. Transient kinetic analysis reveals that the major rate‐limiting step is the closure of the substrate‐specificity loop prior to hydride transfer, in line with other LDHs. The five‐residue insertion in this loop markedly increases substrate specificity compared with the human muscle and heart isoforms.