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Lysophospholipid Acyltransferases and Arachidonate Recycling in Human Neutrophils
Open accessAbstract
The cycle of deacylation and reacylation of phospholipids plays a critical role in regulating availability of arachidonic acid for eicosanoid production. The major yeast lysophospholipid acyltransferase, Ale1p, is related to mammalian membrane-bound O-acyltransferase (MBOAT) proteins. We expressed four human MBOATs in yeast strains lacking Ale1p and studied their acyl-CoA and lysophospholipid specificities using novel mass spectrometry-based enzyme assays. MBOAT1 is a lysophosphatidylserine (lyso-PS) acyltransferase with preference for oleoyl-CoA. MBOAT2 also prefers oleoyl-CoA, using lysophosphatidic acid and lysophosphatidylethanolamine as acyl acceptors. MBOAT5 prefers lysophosphatidylcholine and lyso-PS to incorporate linoleoyl and arachidonoyl chains. MBOAT7 is a lysophosphatidylinositol acyltransferase with remarkable specificity for arachidonoyl-CoA. MBOAT5 and MBOAT7 are particularly susceptible to inhibition by thimerosal. Human neutrophils express mRNA for these four enzymes, and neutrophil microsomes incorporate arachidonoyl chains into phosphatidylinositol, phosphatidylcholine, PS, and phosphatidylethanolamine in a thimerosal-sensitive manner. These results strongly implicate MBOAT5 and MBOAT7 in arachidonate recycling, thus regulating free arachidonic acid levels and leukotriene synthesis in neutrophils.
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Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis
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Mancina, R. M., Dongiovanni, P., Petta, S., Pingitore, P., Meroni, M., Rametta, R., Borén, J., Montalcini, T., Pujia, A., Wiklund, O., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.032 · Cited by 676
Buch, S., Stickel, F., Trépo, E., Way, M., Herrmann, A., Nischalke, H. D., Brosch, M., Rosendahl, J., Berg, T., Ridinger, M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3417 · Cited by 565
Metadata
- Authors
- Gijón, M. A., Riekhof, W. R., Zarini, S., Murphy, R. C., & Voelker, D. R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 283
- Issue
- 44
- Pages
- 30235-30245
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2080092217
- Cited by
- 226
- References
- 2
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Gijón, M. A., Riekhof, W. R., Zarini, S., Murphy, R. C., & Voelker, D. R. (2008). Lysophospholipid Acyltransferases and Arachidonate Recycling in Human Neutrophils. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m806194200
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