Heme polymerase

Chloroquine (Aralen) is one of several 4-aminoquino-line derivatives that display antimalarial activity. Chloroquine is particularly effective against intraerythrocytic forms because it is concentrated within the parasitized erythrocyte. This preferential drug accumulation appears to occur as a result of specific uptake mechanisms in the parasite. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++-calmodulin-mediated mechanisms. It also accumulates in the parasite s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. 

Chou, A. C., and Fitch, C. D. (1992). Heme polymerase Modulation by chloroquine treatment of a rodent malaria. Life Sci. 51,2073-2078. 

The mechanism of malaria pigment s biosynthesis is unique and involves a putative heme polymerase enzyme that is associated with the aggregated heme and functions at the low pH of the food vacuole (6,7). Recent work demonstrates that heme-aggregation is inhibited by the quinine family of antimalarials... 

The heme coordination polymer which results from the heme polymerase activity of the plasmodium parasite is an insoluble crystalline solid with prc ionate interheme links. How the quinine antimalarials inhibit heme polymerase and how this enzyme is associated with jS-hematin remain important, albeit poorly understood, aspects of this biochemistry. Furthermore, heme detoxification by malaria is the only currently recognized example of iron excretion. The homeostasis of iron is usually srictly controlled, and excess is usually stored in ferritin for subsequent... 

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