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Home / Malaria Q&A / Malaria Drug Binding Site

Malaria Drug Binding Site

March 14, 2012 By Malaria Q&A Leave a Comment

QUESTION

What is malaria, and drug binding site?

ANSWER

Malaria is caused by a single-celled protozoan parasite of the genus Plasmodium. Five kinds of Plasmodium are known to infect people: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

There is no one drug binding site with respect to malaria: different anti-malarial drugs have different modes of action, and not all are well described. I will briefly outline the proposed mechanism of action of two of the most common types of anti-malarials: artemisinin (and derivatives) and chloroquine (quinine is thought to act similarly to chloroquine).

Artemisinin is thought to have anti-malarial properties by virtue of possessing an endoperoxide moiety, or double oxygen bridge (-Carbon-Oxygen-Oxygen-Carbon). In the presence of intracellular free ion, this moiety is converted by a chemical reaction to “free radicals”, atoms with unpaired electrons which are highly reactive. The free radicals act as alkylating agents and induce cell death, but only those that are already pathologically crippled, for example due to malaria infection. Another hypothesis is that the free radicals directly damage the malaria parasite.

Chloroquine is thought to act by causing buildup of the toxic by-product of hemoglobin metabolism, heme – the malaria parasite usually converts heme to hemozoin, a non-toxic crystal, and stores it in the digestive vacuole. When chloroquine diffuses into an infected red blood cell, it reacts with heme to “cap” it, preventing further conversion into hemozoin. Moreover, chloroquine also converts hemozoin into a highly toxic substance called the FP-Chloroquine complex. This build-up of toxicity leads to breakdown of the cell membrane, and eventual cell death and autodigestion.

Filed Under: Malaria Q&A Tagged With: alkylating agents, Artemisinin, causes of malaria, cell death, Chloroquine, endoperoxide moiety, FP-Chloroquine complex, free radicals, heme, hemoglobin, hemozoin, mechanisms of anti-malarials, Plasmodium, Plasmodium Falciparum, Plasmodium Knowlesi, Plasmodium malariae, Plasmodium Ovale, Plasmodium Vivax, protozoan, single-celled

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