SLC1 and SLC4 Encode Partially Redundant Acyl-Coenzyme A 1-Acylglycerol-3-phosphate O-Acyltransferases of Budding Yeast

Phosphatidic acid is the intermediate, from which all glycerophospholipids are synthesized. In yeast, it is generated from lysophosphatidic acid, which is acylated by Slc1p, an sn-2-specific, acyl-coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal and d...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-10, Vol.282 (42), p.30845-30855
Main Authors: Benghezal, Mohammed, Roubaty, Carole, Veepuri, Vijayanath, Knudsen, Jens, Conzelmann, Andreas
Format: Article
Language:English
Subjects:
Acyl Coenzyme A - chemistry
Acyl Coenzyme A - genetics
Acyl Coenzyme A - metabolism
Acyltransferases - chemistry
Acyltransferases - genetics
Acyltransferases - metabolism
Amino Acid Motifs - physiology
Down-Regulation - physiology
Dyneins
Fatty Acids - chemistry
Fatty Acids - genetics
Fatty Acids - metabolism
Gene Deletion
Gene Expression Regulation, Enzymologic - physiology
Glycerophospholipids - biosynthesis
Glycerophospholipids - chemistry
Glycerophospholipids - genetics
Lipid Metabolism - physiology
Lysophospholipids - metabolism
Mass Spectrometry
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Microsomes - enzymology
Phosphotransferases (Alcohol Group Acceptor) - chemistry
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Substrate Specificity - physiology
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Summary:Phosphatidic acid is the intermediate, from which all glycerophospholipids are synthesized. In yeast, it is generated from lysophosphatidic acid, which is acylated by Slc1p, an sn-2-specific, acyl-coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal and does not eliminate all microsomal 1-acylglycerol-3-phosphate O-acyltransferase activity, suggesting that an additional enzyme may exist. Here we show that SLC4 (Yor175c), a gene of hitherto unknown function, encodes a second 1-acyl-sn-glycerol-3-phosphate acyltransferase. SLC4 harbors a membrane-bound O-acyltransferase motif and down-regulation of SLC4 strongly reduces 1-acyl-sn-glycerol-3-phosphate acyltransferase activity in microsomes from slc1Δ cells. The simultaneous deletion of SLC1 and SLC4 is lethal. Mass spectrometric analysis of lipids from slc1Δ and slc4Δ cells demonstrates that in vivo Slc1p and Slc4p generate almost the same glycerophospholipid profile. Microsomes from slc1Δ and slc4Δ cells incubated with [14C]oleoyl-coenzyme A in the absence of lysophosphatidic acid and without CTP still incorporate the label into glycerophospholipids, indicating that Slc1p and Slc4p can also use endogenous lysoglycerophospholipids as substrates. However, the lipid profiles generated by microsomes from slc1Δ and slc4Δ cells are different, and this suggests that Slc1p and Slc4p have a different substrate specificity or have access to different lyso-glycerophospholipid substrates because of a different subcellular location. Indeed, affinity-purified Slc1p displays Mg2+-dependent acyltransferase activity not only toward lysophosphatidic acid but also lyso forms of phosphatidylserine and phosphatidylinositol. Thus, Slc1p and Slc4p may not only be active as 1-acylglycerol-3-phosphate O-acyltransferases but also be involved in fatty acid exchange at the sn-2-position of mature glycerophospholipids.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M702719200