Hemozoin

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Hemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. Haematophagous organisms such as Malaria parasites (Plasmodium spp.), Rhodnius and Schistosoma digest hemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin.[1] A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. This process is much-studied in Plasmodium since it is an attractive target for developing drugs to treat malaria.

Formation

The monomeric and potentially toxic α-hematin (ferriprotoporphyrin IX) is detoxified by biocrystallization into insoluble, chemically inert ß-hematin crystals (hemozoin).[2] [3] Several mechanisms have been proposed for this reaction and the area is controversial, with membrane lipids,[4][5] histidine-rich proteins,[6] or even a combination of the two,[7] being proposed to catalyse the formation of hemozoin.

Structure

In ß-hematin a unique iron oxygen coordinate bond links the central iron of one heme to the oxygen of the carboxylate side chain of the adjacent heme. β-hematin can either be a cyclic dimer or a linear polymer [8], a polymeric form has never been found in hemozoin.[9] Hemozoin crystals have a distinct triclinic structure and are weakly magnetic. They also exhibit optical dichroism, which means that they absorb light more strongly along their length than across their width, and this allows the automated detection of malaria. Hemozoin is produced in a form that under the action of an applied magnetic field gives rise to an induced optical dichroism characteristic of the hemozoin concentration and precise measurement of this induced dichroism may be used to determine the level of malarial infection. [10]

References

  1. Egan TJ (2008). "Haemozoin formation". Mol. Biochem. Parasitol. 157 (2): 127–36. doi:10.1016/j.molbiopara.2007.11.005. PMID 18083247. Unknown parameter |month= ignored (help)
  2. Fitch CD, Kanjananggulpan P. (1987). "The state of ferriprotoporphyrin IX in malaria pigment". J Biol Chem. 262 (32): 15552–5. PMID 3119578. Unknown parameter |month= ignored (help)
  3. Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK (2000). "The structure of malaria pigment beta-haematin". Nature. 404 (6775): 307–10. doi:10.1038/35005132. PMID 10749217. Unknown parameter |month= ignored (help)
  4. Bendrat K, Berger BJ, Cerami A (1995). "Haem polymerization in malaria". Nature. 378 (6553): 138–9. doi:10.1038/378138a0. PMID 7477315. Unknown parameter |month= ignored (help)
  5. Dorn A, Vippagunta SR, Matile H, Bubendorf A, Vennerstrom JL, Ridley RG (1998). "A comparison and analysis of several ways to promote haematin (haem) polymerisation and an assessment of its initiation in vitro". Biochem. Pharmacol. 55 (6): 737–47. PMID 9586945. Unknown parameter |month= ignored (help)
  6. Sullivan DJ, Gluzman IY, Goldberg DE (1996). "Plasmodium hemozoin formation mediated by histidine-rich proteins". Science (journal). 271 (5246): 219–22. PMID 8539625. Unknown parameter |month= ignored (help)
  7. Pandey AV, Babbarwal VK, Okoyeh JN; et al. (2003). "Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids". Biochem. Biophys. Res. Commun. 308 (4): 736–43. PMID 12927780. Unknown parameter |month= ignored (help)
  8. Lemberg R, Legge JW (1949). "Hematin compounds and bile pigments". Interscience, New York.
  9. Hempelmann E, Marques HM. (1994). "Analysis of malaria pigment from Plasmodium falciparum". J Pharmacol Toxicol Methods. 32 (1): 25–30. PMID 7833503. Unknown parameter |month= ignored (help)
  10. Newman DM, Heptinstall J, Matelon RJ, Savage L, Wears ML, Beddow J, Cox M, Schallig HD, Mens P (2008). "A magneto-optic route towards the in-vivo diagnosis of malaria: preliminary results and pre-clinical trial data". Biophys J. Apr 4. PMID 18390603.

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