ADDITION OF LIPID SUBSTITUENTS OF MAMMALIAN PROTEIN GLYCOSYLPHOSPHOINOSITOL ANCHORS

A single metabolic path leading to synthesis of ether lipids is known in animal cells, the major products of which are plasmalogens. To lear n whether this peroxisomal path is also responsible for the synthesis of base-resistant lipid components of glycosylphosphoinositol (GPI)-an chored membrane proteins, we have investigated the structure of anchor precursor mannolipids both in wild-type cells (CHO-K1 and a macrophag e-like line, RAW 264.7) and in two corresponding mutant cells in which ether lipid biosynthesis is severely impaired. We observe that the pr ecursor mannolipids of both the wild-type and mutant cells do not incl ude alkylglycerol. Nevertheless, both wild-type and mutant cells expre ss cell surface GPI-anchored placental alkaline phosphatase (AP) which includes alkali-resistant hydrophobic chains in its anchor moiety. Th us, (i) in normal AP GPI anchor synthesis, any ether-linked substituen ts must be added either immediately before, during, or after anchor ad dition to AP, and (ii) the classical peroxisomal path for ether lipid synthesis appears not to contribute to the synthesis of GPI anchors.