BIOCHEMISTRY AND MOLECULAR-GENETICS OF LEISHMANIA GLUCOSE TRANSPORTERS

Glucose is utilized as a significant source of metabolic energy by Lei shmania parasites. This sugar is accumulated by the parasite via a spe cific carrier-mediated transport system located in the parasite membra ne. Parasites may also contain another transporter that shuttles gluco se between the cytoplasm and the glycosome, a membrane-bound organelle where the early steps of glycolysis occur. The transport systems of b oth the insect stage promastigotes and the intracellular amastigotes h ave been characterized and shown to have kinetic properties that are c onsistent with the different physiological environments of the insect gut and the macrophage phagolysosome. Several genes have been cloned f rom Leishmania species which encode proteins with substantial sequence similarity to glucose transporters from mammals and lower eukaryotes. Two of these genes are expressed preferentially in the promastigote s tage of the life cycle, where glucose is more readily available and mo re rapidly transported and metabolized than in the intracellular amast igotes. One of these two developmentally-regulated genes has been func tionally expressed in Xenopus oocytes and shown to encode a glucose tr ansporter. A third gene encodes a protein that is also a member of the glucose transporter family on the basis of sequence similarity and pr oposed secondary structure. However, the significant differences betwe en this protein and the other two suggest that it is likely to transpo rt a different substrate. Functional expression will be required to de fine the specific biochemical role of each gene within the parasite.