Plasmodium and host lactate dehydrogenase molecular function and biological pathways: implication for antimalarial drug discovery.
Lactate dehydrogenase is an enzyme that catalyses the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD(+). Lactate dehydrogenase is present at high levels in humans and Plasmodium spp. However, the function of lactate dehydrogenase in malarial infection is not well characterized. In this investigation, a new gene ontology technology is used to predict molecular function and biological pathways of lactate dehydrogenase. In comparison with human lactate dehydrogenase, the P. falciparum lactate dehydrogenase has similar molecular functions such as L-lactate dehydrogenase activity. Furthermore, P. falciparum lactate dehydrogenase has L-malate dehydrogenase activity. Although the amino acid sequences for human and P. falciparum lactate dehydrogenase are very different, the molecular functions are similar. This suggests that any non-selective therapeutic treatment aimed at blocking P. falciparum lactate dehydrogenase function may affect human lactate dehydrogenase. In contrast, a selective lactate dehydrogenase inhibitor targeting the l-malate dehydrogenase function of P. falciparum and its corresponding tricarboxylic acid cycle provides an attractive therapeutic opportunity.
Wiwanitkit
Viroj
V
Department of Laboratory Medicine, Chulalongkorn University, Bangkok 10330, Thailand. wviroj@yahoo.com
D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*; D016415:Sequence Alignment
D000962:Antimalarials; D007770:L-Lactate Dehydrogenase