Metabolism of ether lysophospholipids in Leishmania donovani promastigotes.

Ether lysophospholipids, 1-O-[1'-14C]octadec-1'-enyl-sn-glycero-3-phosphoethanolamine (A) and -phosphocholine (B) as well as 1-O-[1'-14C]octadecyl-sn-glycero-3-phosphoethanolamine (C) and -phosphocholine (D) were taken up rapidly and metabolized extensively in Leishmania donovani promastigotes. Degradation to neutral lipids occurred first, followed by incorporation into phospholipids. Incubation of the cells with (A) or (B) revealed the stability of the O-[1-14C]octadec-1-enyl group up to 15 h, indicating the absence of any O-alk-1-enyl cleavage enzymes. Most of the radioactivity was found in 1-O-alkenyl-2-acyl-glycerophosphoethanolamine and 1-O-alkenyl-2,3-diacylglycerol. 1-O-Alkenyl-2-acyl-glycerophosphocholine was detected only after incubation with substrate (B). In contrast to the O-alk-1-enyl residue, the O-[1-14C]octadecyl moiety in substrate (C) and (D) could be converted into the O-[1-14C]octadec-1-enyl moiety or cleaved, yielding labelled acyl groups. Following 5 h incubation with substrate (C), most of the incorporated radioactivity was associated with 1-O-[1'-14C]octadec-1'-enyl-2-acyl-glycerophosphoethanolamine, 1-O-[1'-14C]octadecyl-2,3-diacylglycerol and 1-O-[1'-14C]octadecyl-2-acyl-glycerophosphoinositol. After 15 h minor amounts of label appeared in diacyl glycerophosphocholine. Similar labelling patterns were obtained with the choline analogue (D), except that 1-O-[1'-14C]octadecyl-2-acyl-glycerophosphocholine was found additionally. Incubations of the four labelled ether lysophospholipids with cell homogenates showed the presence of a lysophospholipase D and a phosphohydrolase. There was no specificity towards different ether residues or phosphobase moieties. Formation of alkyl- and alkenylglycerol, respectively, was stimulated by Mg2+ ions and the phosphohydrolase was inhibited by NaF. The results support the conclusion that the specific pattern of ether phospholipids in L. donovani cells is due to a pronounced specificity of the biosynthetic enzymes. Enzymes of the catabolic reactions are of low specificity or absent, such as plasmalogenases.