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African parasite makes component of fat differently from all other organisms

Studying the parasite that causes African sleeping sickness, scientists at Johns Hopkins have discovered a previously unknown way of making fatty acids, a component of fat and the outer layer of all cells. The find unveils more about the biology of this hard-to-kill parasite and could lead to a target for designing new drugs to fight the illness that infects a half-million people and kills 50,000 a year worldwide.

Results of the study, in the Aug. 25 issue of Cell, "show that this is a completely new biochemical pathway for making fatty acids," says Soo Hee Lee, Ph.D., a postdoctoral fellow in the Department of Biological Chemistry at the Institute for Basic Biomedical Sciences at Hopkins. "It may be that the enzymes in the pathway could be good targets for designing drugs to treat sleeping sickness."

The single-celled trypanosome that causes African sleeping sickness, transmitted between humans and animals by bloodsucking tsetse flies, goes through several different stages in its life cycle. One such form is harbored by the insect and the other multiplies in a host's bloodstream.

There, the parasite avoids detection by the human immune system by replacing each of the 10 million proteins on its outer layer - known as the cell membrane - with different proteins that are not recognized by immune cells. These proteins are attached to the cell membrane by an anchor composed in part of a fatty acid only 14 units long - dubbed myristate -- whereas typically, in other organisms, these types of anchors contain longer fatty acids, generally 16 or 18 units long.

"For many years we thought the parasite had to get the myristate from its human host because we never could see any evidence that it could make the fatty acid itself," says Paul Englund, Ph.D., a professor of biological chemistry in the Institute of Basic Biomedical Sciences at Hopkins. "Several years ago we found that it does actually make myristate as well as other fatty
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
24-Aug-2006


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