The pivotal role of carbonic anhydrase in malaria infection.
Carbon dioxide (CO2) is essential for the growth of intraerythrocytic malaria parasites to synthesize pyrimidine through CO2 fixation and to regulate intracellular pH. CO2 transport across the plasma membrane of erythrocytes is facilitated by carbonic anhydrase (CA). With the use of electron microscopy and CA-specific Hansson's stain, CA is found also in all the intraerythrocytic stages of Plasmodium falciparum. When CA inhibitors, including acetazolamide, potassium iodide, and sodium deoxycholate, were added to continuous culture of P. falciparum, they, particularly sodium deoxycholate, produced a marked reduction in parasitemia. These results explain the biochemical basis of some of the clinical conditions associated with malaria and strongly suggest that CA inhibitors have potential as a new class of antimalarials.
Sein
K K
KK
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Aikawa
M
M
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology* / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D018512:Parasitemia / Q000097:blood / Q000201:enzymology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity*
D000962:Antimalarials; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases