The uptake and metabolism of lyso‐phospholipids by Saccharomyces cerevisiae

Abstract

We have characterized the uptake and metabolism of lyso‐PtdEtn and lyso‐PtdCho by yeast. The reactions involved in the utilization of these compounds are collectively termed the exogenous lysolipid metabolism (ELM) pathway, and mutants defective in both the uptake and acylation steps of the ELM pathway have been isolated. The P‐type ATPases Dnf1p and Dnf2p, in consort with their β‐subunit Lem3p, catalyze the transport reaction. An enzyme designated Ale1p (acyltransferase for lyso‐PtdEtn), a member of the membrane bound O‐acyltransferase (MBOAT) family, serves as the acyltransferase component of this pathway for both lyso‐PtdEtn and lyso‐PtdCho. Ale1p is the major lyso‐phospholipid acyltransferase in yeast, and shows a preference for mono‐unsaturated acyl‐CoA species, and a broad lyso‐lipid substrate specificity that includes lyso‐PtdOH, lyso‐PtdGro, lyso‐PtdIns, and lyso‐PtdSer. The ale1Δ mutant is devoid of lyso‐PtdEtn and lyso‐PtdCho acyltransferase activities, making this strain an ideal host for expression and analysis of putative acyltransferases from other species. We now report the expression and enzymatic characterization of previously uncharacterized human MBOAT family members in an ale1Δ mutant yeast strain. Supported by NIH grants GM32453 (to D.R.V), GM076798 (to W.R.R.), and HL25785 (to R.C.M.), and by American Cancer Society grant PF‐06‐288‐01‐CSM (to W.R.R.)