The deamination of adenosine and adenosine monophosphate in Plasmodium falciparum-infected human erythrocytes: in vitro use of 2'deoxycoformycin and AMP deaminase-deficient red cells.
The role of enzymatic deamination of adenosine monophosphate (AMP) and adenosine in the in vitro growth of the malaria parasite Plasmodium falciparum was investigated by means of human red cells deficient in AMP deaminase to which the adenosine deaminase inhibitor 2'-deoxycoformycin was added. Malaria parasites grew normally in red cells lacking one or both of these enzyme activities. As a further probe of adenosine triphosphate (ATP) catabolism, both infected and uninfected RBCs were incubated with NaF (with and without 2'-deoxycoformycin) and the purine nucleotide/nucleoside content was analyzed by high-performance liquid chromatography (HPLC). Uninfected RBCs lacking either AMP or adenosine deaminase were able to bypass the enzyme block and degrade ATP to hypoxanthine. Uninfected RBCs with both deaminases blocked were unable to produce significant quantities of hypoxanthine. On the other hand, infected RBCs were able to bypass blockade of both deaminases and produce hypoxanthine and adenosine. These findings establish that deamination of adenosine and/or AMP are not essential for plasmodial growth. However, further work will be required to elucidate the pathways that permit the parasites to bypass these catabolic steps.
Roth
E
E
Department of Genetics, Institute for Developmental Research, Aichi, Japan.
Ogasawara
N
N
Schulman
S
S
D000659:AMP Deaminase / Q000097:blood / Q000172:deficiency*; D000241:Adenosine / Q000097:blood*; D000249:Adenosine Monophosphate / Q000097:blood*; D000328:Adult; D000818:Animals; D003070:Coformycin / Q000031:analogs & derivatives; D003641:Deamination; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism / Q000469:parasitology*; D005260:Female; D006801:Humans; D008288:Malaria / Q000097:blood / Q000201:enzymology / Q000469:parasitology; D009709:Nucleotide Deaminases / Q000172:deficiency*; D015649:Pentostatin; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D012263:Ribonucleosides / Q000031:analogs & derivatives
D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D000249:Adenosine Monophosphate; D009709:Nucleotide Deaminases; D000659:AMP Deaminase; D000241:Adenosine