Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria

Approximately 70% of the initial ferriprotoporphyrin IX polymerizing activi ty in cell-free preparations of erythrocytes infected with Plasmodium bergh ei was recovered in a chloroform extract. No polymerizing activity remained in the residue. In studies to identify substances that promote FP polymeri zation, arachidonic, linoleic, oleic, and palmitoleic acids, 1-mono- and di -oleoylglycerol, and the detergents, SDS, Tween 80, and n-octyl-glucopyrano side, were active. Tri-oleoylglycerol, cholesterol, di-oleoylphosphatidylet hanolamine, and stearic and palmitic acids were inactive. The model lipid, monooleoylglycerol (250 nmol), co-precipitated with FP from a 0.09 M acetat e medium at pH 5 and promoted the polymerization of 215 nmol (61%) of the f erriprotoporphyrin IX in the precipitate during a 24-h incubation at 37 deg rees C. Polymerization was maximal at pH 5, it was approximately linear for 2 h, and it continued at a decreasing rate for 24 h. The polymer contained exclusively ferriprotoporphyrin IX (97 +/- 1.3%, mean +/- S.E., n = 4) and exhibited the solubility and the electronic absorption and infrared spectr al characteristics of the sequestered ferriprotoporphyrin IX of hemozoin. D etergents presumably promote polymerization in an acid medium by helping to dissolve monomeric FP. We suggest that unsaturated lipids co-precipitate w ith FP in the parasite's acidic food vacuole and also dissolve sufficient m onomeric FP to allow polymerization. (C) 1999 Elsevier Science B.V. All rig hts reserved.