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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Melvin A Ambele, Timothy J Egan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-337) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

Both authors conceived and designed the study. MAA performed the experiments, data analyses and prepared the figures and tables. Both authors drafted the manuscript. Both authors read and approved the final manuscript.

Abstract

Background

The malaria parasite disposes of host-derived ferrihaem (iron(III)protoporphyrin IX, Fe(III)PPIX) by conversion to crystalline haemozoin in close association with neutral lipids. Lipids mediate synthetic haemozoin (β-haematin) formation very efficiently. However, the effect on reaction rates of concentrations of lipid, Fe(III)PPIX and physiologically relevant ions and biomolecules are unknown.

Methods

Lipid emulsions containing Fe(III)PPIX were prepared in aqueous medium (pH 4.8, 37°C) to mediate β-haematin formation. The reaction was quenched at various times and free Fe(III)PPIX measured colorimetrically as a pyridine complex and the kinetics and yields analysed. Products were also characterized by FTIR, TEM and electron diffraction. Autofluorescence was also used to monitor β-haematin formation by confocal microscopy.

Results

At fixed Fe(III)PPIX concentration, β-haematin yields remained constant with decreasing lipid concentration until a cut-off ratio was reached whereupon efficiency decreased dramatically. For the haemozoin-associated neutral lipid blend (NLB) and monopalmitoylglycerol (MPG), this occurred below a lipid/Fe(III)PPIX (L/H) ratio of 0.54. Rate constants were found to increase with L/H ratio above the cut-off. At 16 μM MPG, Fe(III)PPIX concentration could be raised until the L/H ratio reached the same ratio before a sudden decline in yield was observed. MPG-mediated β-haematin formation was relatively insensitive to biologically relevant cations (Na+, K+, Mg2+, Ca2+), or anions (H2PO4, HCO3, ATP, 2,3-diphosphoglycerate, glutathione). Confocal microscopy demonstrated β-haematin formation occurs in association with the lipid particles.

Conclusions

Kinetics of β-haematin formation have shown that haemozoin-associated neutral lipids alone are capable of mediating β-haematin formation at adequate rates under physiologically realistic conditions of ion concentrations to account for haemozoin formation.
Zusatzmaterial
Authors’ original file for figure 1
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Literatur
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