LEISHMANIA-DONOVANI POSSESS A NADPH-DEPENDENT ALKYLGLYCEROL CLEAVAGE ENZYME

Leishmania parasites possess an abundance of ether-linked hydrocarbons as components of phospholipids and glycosylphosphatidylinositol ancho rs of glycoproteins and polysaccharides, including important surface m olecules such as lipophosphoglycan (LPG) and glycosylinositolphospholi pids (GIPLs). Cleavage of the ether bond is an important feature in th e turnover pathway of alkylglycerols. In mammals, ether lipid cleavage activity requires a pteridine cofactor (H-4-biopterin), suggesting th e potential for linkage between the unusual Leishmania pteridine metab olic pathways and lipid metabolism. In this study, we partially purifi ed and characterized an activity in L. donovani capable of cleaving th e ether lipid 1-O-alkyl[H-3]glycol. Unlike the mammalian enzyme but li ke that of Tetrahymena, the Leishmania enzyme required NADPH rather th an H-4-biopterin. The use of divergent cofactors by the parasite and m ammalian enzymes may provide a basis for the design of anti-parasitic drugs targeting ether-linked lipid metabolism. (C) 1996 Academic Press Inc.