A novel glycosyl phosphatidylinositol in african trypanosomcs: A possible catabolic intermediate

Grant from N1H (AI 21334) and Wellcome Trust Prize Travelling Research Fellowship. The surface coat of African trypanosomes is composed of variant surface glycoprotein molecules, each of which is anchored to the plasma membrane by a glycosyl phosphatidylinositol (GPI)- The GPI anchor is synthesized as a precursor, glycolipid A, which is attached en bloc to the VSG polypcptide. Another abundant GPI is an inositol-acylated version of the GPI precursor, glycolipid C, which may serve as a reservoir for excess GPIs or as the first intermediate in GPI catabolism. Both glycolipids A and C are myristoylated on the glycerot moiety by highly specific remodeling and exchange reactions. We now report a novel acylation reaction forming a glycolipid which we characterized as a lyso species, Man-4GlcN(acyl)inositoI<phosphopalmitoylglycerol. We detected this species, designated glycolipid X, in trypanosomes permeabilized with 0.03% digitonin and incubated with [H]palmitoyl-CoA. The radiotabeled palmitate was exclusively incorporated into the glycerol moiety of this glycolipid. Glycolipid X is a transient species with its formation being inhibited by Mg2+ and its breakdown being inhibited by Co2. We have tentatively identified breakdown products of this glycolipid and further speculate that it may be an intermediate in the catabolism of excess GPIs.