Digestive vacuole

Lead material tracks through digestive vacuoles and enters cytoplasm of... 

Scheme I. Ordered Catabolic Pathway of Hemoglobin Degredation within the Digestive Vacuole of P. falciparum.

While hemoglobin proteolysis yields needed amino acids, it also releases toxic free heme. Fig. (1) Upon proteolysis, heme is released into the digestive vacuole where the iron of the heme moiety is oxidized from the predominantly ferrous (+2) state to the ferric (+3) state. Estimates suggest... 

Another possible participant in hemozoin nucleation is the histidine-rich protein (HRP). Using monoclonal antibodies to probe the proteins of the digestive food vacuole of P. falciparum, Sullivan et al. identified two histidine-rich proteins, HRP II and HRP III, and demonstrated that these proteins could mediate the formation of hemozoin [37]. HRP II (Mr 35 kD) contains 51 repeats of the sequence Ala-His-His (76% of the mature protein is histidine and alanine) [38], while HRP III (Mr 27 kD) contains 28 Ala-His-His sequences (56% of the mature protein is histidine and alanine) [39]. While a clone lacking both HRP II and III has been shown to produce hemozoin, a third protein which cross reacted with anti-HRP monoclonal antibodies has also been found in the digestive vacuole of this strain. Although this protein has not been isolated or shown to mediate hemozoin formation, a candidate is HRP IV (Mr 10 kD) which is 31% histidine [40]. 

The malaria parasite, P. falciparum, obtains most of its requisite amino acids from the catabolism of host hemoglobin via a defined metabolic pathway which occurs in specialized digestive vacuoles at low pH (4.8-5.2). Ironically, one molecule of hemoglobin contains four molecules of... 

Spiller DG, Bray PG, Hughes RH, et al. The pH of the Plasmodium falciparum digestive vacuole holy grail or dead-end trail Trends Parasitol. 2002 18 441M44. 

Cells would have persisted only because of extreme efficiency in self-maintenance. In cell compartments the catalyst concentration would be a hundred to a thousand times higher than on the outside where everything is large compared to the picoliter size cell. A few protons, two to three in alysosome (a digestive vacuole), would produce pH values of 1 (the equivalent of 0.1 molar hydrochloric acid), and two enzymes in that space would bring its concentration into the millimolar range. In a cell the affinity of the enzyme for its substrate determines the speed of the reaction as opposed to thermodynamic limitations of the chemical transformation per se. 

During hemoglobin degradation, free heme, ferriprotoporphyrin-IX or Fe(II) PPIX (Fig. 2) is released in the digestive vacuole. The toxicity of heme to the parasite has been demonstrated [27-30] it is supposed to cause the disruption of metabolic functions by means of peroxidation of membranes and inhibitions of enzymes via the generation of oxidative free radicals [31],... 

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