title: Plasmodium falciparum-infected erythrocytes contain an adenylate cyclase with properties which differ from those of the host enzyme.
abstract: It has been postulated that differentiation of the human malaria parasite, Plasmodium falciparum, is controlled by cAMP levels. We have determined that P. falciparum synthesizes an adenylate cyclase with several properties distinct from those of the mammalian host cell enzyme. Adenylate cyclase activity was compared in P. falciparum-infected erythrocytes, isolated parasites free of host cell material, and uninfected erythrocyte membranes. The parasite enzyme was unaffected by GTP gamma S, AlF4-, and forskolin, while the erythrocyte enzyme was markedly stimulated by each of these compounds. The parasite adenylate cyclase also exhibited a striking preference for Mn2+ over Mg2+, which was not evident in the erythrocyte enzyme. Moreover, differing cation and pH sensitivities were observed for adenylate cyclase activity in the two cell types. When infected and uninfected erythrocytes were compared, the basal adenylate cyclase activity of infected cells was 7 and 49 times that measured in uninfected erythrocytes in the presence of Mg2+ and Mn2+, respectively. Furthermore, adenylate cyclase activity in infected cells exhibited properties typical of the parasite enzyme. This indicates that synthesis of the parasite enzyme rather than stimulation of the host enzyme accounts for the increased activity in infected cells.
authors.affiliation: Department of Physiology, Tufts University School of Medicine, Boston, MA.
authors.forename: L K
authors.initials: LK
authors.lastname: Read
authors.forename: R B
authors.initials: RB
authors.lastname: Mikkelsen
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002712:Chlorides; D005576:Colforsin / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000469:parasitology*; D019204:GTP-Binding Proteins / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D015636:Magnesium Chloride / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D015636:Magnesium Chloride; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008345:Manganese; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C025340:manganese chloride