Heme metabolism of Plasmodium is a major antimalarial target.
The malarial parasite manifests unique features of heme metabolism. In the intraerythrocyte stage it utilizes the host hemoglobin to generate amino acids for its own protein synthesis, but polymerizes the acquired heme as a mechanism for detoxification. At the same time the parasite synthesizes heme de novo for metabolic use. The heme biosynthetic pathway of the parasite is similar to that of hepatocytes and erythrocytes. However, while the parasite makes its own delta-aminolevulinate (ALA) synthase that is immunochemically different from that of the host, it imports ALA dehydrase and perhaps the subsequent enzymes of the pathway from the host red cell. Many schizonticidal drugs such as chloroquine and artemisinin act by interfering with the heme metabolism of the parasite and there is scope to design new molecules based on the unique features of this metabolic machinery in the parasite.
Padmanaban
G
G
Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.
Rangarajan
P N
PN
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000097:blood / Q000188:drug therapy / Q000469:parasitology; D008954:Models, Biological; D010961:Plasmodium / Q000187:drug effects* / Q000378:metabolism*; D000623:Porphobilinogen Synthase / Q000378:metabolism
D000962:Antimalarials; D006418:Heme; D002738:Chloroquine; D000624:5-Aminolevulinate Synthetase; D000623:Porphobilinogen Synthase