Purine metabolism during continuous erythrocyte culture of human malaria parasites (P. falciparum).
Through use of techniques for continuous erythrocyte culture and novel chromatographic procedures we have identified the major salvage pathways for metabolism of purine bases in P. falciparum infected human erythrocytes. The malaria parasitized erythrocyte (PRBC) differs from the unparasitized mature erythrocyte (RBC) in the following ways: PRBC primarily utilize hypoxanthine for synthesis of both adenylates and guanylates; PRBC incorporate the base guanine into guanylates at a higher rate than control RBC, PRBC do not appear to use adenine effectively due to an overwhelming competition for this base by the whole erythrocyte population; although PRBC cultures show an initial increase in [ATP] this change is interpreted to reflect a generalized RBC response to malaria infection and not a response restricted to PRBC. Our observations have identified a purine pathway involving adenylosuccinate (AMPs) present only in PRBC (HYP leads to IMP leads to AMPS leads to AMP). They also demonstrate the importance of guanylate synthesis to the malaria parasite. We have shown that the purine metabolism of unparasitized erythrocytes is perturbed during malaria infection, an effect reflected primarily by an increase in erythrocyte ATP. This increase in host erythrocyte ATP not only improves metabolic conditions for parasite growth but also places a demand on available purine resources that has implications for the severe disruption of normal erythrocyte function.
D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002250:Carbon Radioisotopes; D004912:Erythrocytes / Q000382:microbiology*; D006147:Guanine / Q000378:metabolism; D006801:Humans; D007042:Hypoxanthines / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*
D002250:Carbon Radioisotopes; D007042:Hypoxanthines; D011687:Purines; D006147:Guanine; D000255:Adenosine Triphosphate; D000225:Adenine; D000241:Adenosine