Erythrocyte membranes convert monomeric ferriprotoporphyrin IX to β-hematin in acidic environment at malarial fever temperature.
Hemozoin production makes it possible for intraerythrocytic malaria parasites to digest massive quantities of hemoglobin but still avoid potential ferriprotoporphyrin IX (FP) toxicity, which they cannot decompose further. Some antimalarial drugs, such as chloroquine, work by inhibiting this production, forcing the parasite to starve to death. As part of the efforts to identify possible biological mechanisms of FP polymerization, we have used normal human erythrocyte membranes as a model, to promote β-hematin (β-h) synthesis. Hemin in 35% aqueous dimethyl sulfoxide (DMSO) was reacted with isolated erythrocyte membranes and incubated overnight in sodium acetate buffer, pH 4.8, at 41°C. Infrared spectroscopy and electron microscopy showed that β-h was produced. Hemin in 10% was less effective as the substrate than when it was in 35% DMSO. A high malarial temperature seemed to be necessary, because FP polymerization was less at 37°C than at 41°C. Production was partially inhibited by chloroquine. These observations are of interest because other investigators have reported that membrane lipids mediated FP polymerization, but whole membranes were ineffective. On the other hand, our hypothesis is that the transport vesicles (TV) in malaria parasites could provide the receptor for FP and the lipids that promote hemozoin formation. Erythrocyte membranes may not be directly involved, but Plasmodium species transport hemoglobin in membrane-bound TV into food vacuoles, where hemoglobin catabolism is completed and hemozoin crystals are stored.
Department of Medical Laboratory Sciences, Kuwait University, Kuwait, Arabian Gulf. aurjih@gmail.com
Augustine U
AU
Orjih
Thazhumpal C
TC
Mathew
Preethi T
PT
Cherian
D000328:Adult; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D005334:Fever / Q000503:physiopathology*; D006420:Hemeproteins / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000469:parasitology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D010961:Plasmodium / Q000378:metabolism / Q000472:pathogenicity; D013055:Spectrophotometry, Infrared; D013696:Temperature
D006420:Hemeproteins; C020753:hemozoin; D006427:Hemin