Parasitic strategy for poison control.

Parasitic strategy for poison control

Humans aren't the only organisms with elaborate waste-disposal systems. The malaria parasite Plasmodium falciparum has an unusual way of protecting itself from a toxic by-product of its voracious lifestyle in the human bloodstream, researchers report in the January PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol. 88, No. 2). As scientists unravel the molecular details of this mechanism, they may gain a better understanding of how today's antimalaria drugs work, and perhaps develop more effective treatments.

The single-called P. falciparum feasts on an oxygen-carrying pigment called hemoglobin, sapping red blood cells of more than half their hemoglobin supply. Butthis hearty fare harbors a poisonous ingredient: the iron-rich heme portion of the hemoglobin molecule, which the parasite's digestive process cannot break down. Heme can kill the organism by chemically smashing open its membranes, but P. falciparum avoids that fate by converting heme into a nontoxic pigment called hemozoin, which causes the brown discoloration of the liver, spleen and brain in people with severe malarial infection.

Some scientists have suggested that the parasite accomplishes this conversion by using proteins to sequester the heme. Not so, says biochemist Andrew F.G. Slater of Rockefeller University in New York City.

He and his colleagues discovered that the parasite makes its hemozoin by stringing together heme molecules through a link between the central iron atom of one heme and one of two carboxylate ions sticking off one side of the next heme. They theorize that P. falciparum produces enzymes tht expedite this bonding process, which would otherwise require enormous amounts of chemical energy. Identifying those enzymes might enable chemists to design antimalaria drugs that interfere with their action, Slater says.

Scientists still don't fully understand the action of two of today's major antimalaria drugs, quinine and chloroquine, he adds. They do know, however, that these drugs target the parasite's digestive organ, or food vacuole. Since hemozoin synthesis also occurs in the vacuole, Slater theorizes that the drugs interfere with hemozoin formation, in effect fighting P. falciparum through food poisoning.