Hemozoin crystal

Slater A, Swiggard W, Orton B, Hitter W, Goldberg D, Cerami A, Henderson G. An iron-carboxylate bond links the heme units of malaria pigment. Proc. Natl. Acad. Sci. U.S.A. 1991 88 325-329. Noland G, Briones N, Sullivan D Jr. The shape and size of hemozoin crystals distinguishes diverse Plasmodium species. Mol. Biochem. Parasitol. 2003 130 91-99. 

Inhibition of the nucleation and/or growth of the hemozoin crystals induced by FQ may be explained by the stereoselective binding of FQ with faces thereof. Generally, the two forms, biogenic (hemozoin) and synthetic (P-hematin), of the malaria pigment present three dominant crystal feces [h k 1 of the [100] side surfaces, 010 face that is perpendicular to each other, and the 011 fece that is inclined relative to the c-axis, ending at each end of crystal [85]. Sometimes, the biogenic hemozoin crystals have a face 001, which is perpendicular to the c-axis and that does not develop properly. The 001 face is exposed to the... 

Figure 11.7 Heme groups in different binding situations (a) free heme which is cell toxic (b) In hemoglobin, the heme is bound to a protein backbone (R). Hemoglobin is ordered in a quaternary structure, meaning that four globular a-helical subunits arrange in a tetrahedral shape, (c) Heme is detoxified in hemozoin crystals, which are insoluble.

In a complementary study, a hemozoin crystal was investigated in the same way [79]. Hemozoin is synthesized when the malarial parasite Plasmodiumfalciparum digests the protein and the free heme, which is toxic for the parasite, is leftover. The crystallization of heme yields hemozoin (see Figure 11.7c), which is insoluble in the cell. In this way, the parasite gets rid of the toxic heme while insoluble crystals of hemozoin with a size of a few hundred nanometers are formed. This happens by dimerization of two heme molecules via one of their carboxyl moieties. The other carboxyl group coordinates with the central iron atom (see Figure 11.7c). 

Hemozoin, also known as malaria pigment, is, in teims of its chemical composition, identical to (3-hematin. Hemozoin is formed as a crystallization product of heme under the acidic conditions present in the food vacuole of malarial parasites. In the crystal, the heme molecules are linked into dimers through reciprocal iron-carboxylate bonds to one of the propionate side chains of each porphyrin. The dimers form chains linked by hydrogen bonds. 

A crystal is formed and its characteristics have been recently defined and discussed concerning the mechanism of action of antimalarials interacting with hemozoin formation [35, 36], With the mechanism of biomineralization, the low soluble hemozoin is thus removed from the biological environment of the parasite. 

Figure 4 Physical characterization of hemozoin. (a) The axial propionate linkages between heme units in FIZ are seen by FT-IR fingerprints of C = 0 and C-O stretching at 1664 and 1211 cm , respectively, (b) Characteristic 2 1 peaks are seen at T-. 21° and 24° 28 for (i) native and (ii) synthetic FIZ. Absent from these aggregates is the 23° 28 peak observed in the diffraction pattern of (iii) substrate hemin chloride, (c) Electron micrograph of FIZ in P. falciparum infected RBC where (i) is the host RBC, (ii) is the parasite, and (iii) is the DV. Image reproduced with kind permission of Springer Science and Business Media (23). (d) SEM image of uniform BFI crystals.

Although Fitch et al. (1999) found TAG to be inactive in p-hematin formation Jackson et al. (2004) found MOG as well as mono- and dimyristoyl glycerol to be effective. In contrast, Pisciotta et al. (2007) found MPG to be a potent promoter of heme crystallization as was the combination of 1-stearic-3-palmitic glycerol. A NL blend of MPG/MSG/dipalmitic glycerol (DPG)/ dioleic glycerol (DOG)/dilinoleic glycerol (DLG) (2 4 1 1 1) produced heme crystals rapidly. Of some interest is their observation, the lipid blend crystals did not exactly replicate hemozoin made by P. falciparum (and) may require the presence of non-specific proteins or other molecular species. ... 

Recently, a novel physical method for rapid and sensitive malaria detection in blood has been developed [46-50]. This method— ultraviolet LD MS—is based on the detection of heme (iron protoporphyrin) in blood as a qualitative and quantitative malaria biomarker, both in vitro [46] and in vivo [49,50]. In infected erythrocytes, the parasite sequesters heme from digested hemoglobin in a molecular crystal (malaria pigment or hemozoin). LDMS detects only heme from hemozoin in parasite-infected blood, and not heme, bound to hemoglobin... 

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