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Reference: Riekhof WR, et al. (2007) Lysophosphatidylcholine metabolism in Saccharomyces cerevisiae: the role of P-type ATPases in transport and a broad specificity acyltransferase in acylation. J Biol Chem 282(51):36853-61

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Abstract

We recently described a new route for the synthesis of PtdEtn from exogenous lyso-PtdEtn, which we have termed the exogenous lysolipid metabolism (ELM) pathway. The ELM pathway for lyso-PtdEtn requires the action of plasma membrane P-type ATPases Dnf1p and Dnf2p, and their requisite ss-subunit, Lem3p, for the active uptake of lyso-PtdEtn. In addition, the acyl-CoA dependent acyltransferase, Ale1p, mediates the acylation of the imported lysolipid to form PtdEtn. We now report that these components of the lyso-PtdEtn ELM pathway are also active with lyso-PtdCho as a substrate. Lyso-PtdCho supports the growth of a choline auxotrophic pem1 pem2 strain. Uptake of radiolabeled lyso-PtdCho was impaired by the dnf2 and lem3 mutations. Introduction of a lem3 mutation into a pem1 pem2 background impaired the ability of the resulting strain to grow with lyso-PtdCho as the sole precursor of PtdCho. After import of lyso-PtdCho, the recently characterized lyso-PtdEtn acyltransferase, Ale1p, functioned as the sole lyso-PtdCho acyltransferase in yeast. A pem1 pem2 ale1 strain grew with lyso-PtdCho as a substrate, but showed a profound reduction in PtdCho content when lyso-PtdCho was the only precursor of PtdCho. Ale1p acylates lyso-PtdCho with a preference for monounsaturated acyl-CoA species, and the specific LPCAT activity of Ale1p in yeast membranes is >50 fold higher than the basal rate of de novo aminoglycerophospholipid biosynthesis from PtdSer synthase activity. In addition to lyso-PtdCho, lyso-PtdEtn, and lyso-PtdOH, Ale1p was also active with lyso-PtdSer, lyso-PtdGro, and lyso-PtdIns as substrates. These results establish a new pathway for the net synthesis of PtdCho in yeast, and provide new tools for the study of PtdCho synthesis, transport, and remodeling.

Reference Type
Journal Article
Authors
Riekhof WR, Wu J, Gijon MA, Zarini S, Murphy RC, Voelker DR
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