Lysophospholipid acyltransferases and arachidonate recycling in human neutrophils.
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.
Gijón
Miguel A
MA
Department of Pharmacology, University of Colorado Denver, Aurora, Colorado 80045, USA.
Riekhof
Wayne R
WR
Zarini
Simona
S
Murphy
Robert C
RC
Voelker
Dennis R
DR
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D007249:Inflammation; D013058:Mass Spectrometry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity; D013849:Thimerosal / Q000494:pharmacology; D013997:Time Factors
D008565:Membrane Proteins; D010743:Phospholipids; D012333:RNA, Messenger; D013849:Thimerosal; D016718:Arachidonic Acid; D000217:Acyltransferases; C000616532:MBOAT7 protein, human; D000123:Acetyltransferases; C521271:MBOAT1 protein, human; D008243:1-Acylglycerophosphocholine O-Acyltransferase
FEBS Lett. 2008 Jan 23;582(2):305-9
18154737
J Biol Chem. 2006 Dec 1;281(48):36588-96
17015438
J Biol Chem. 2007 Oct 19;282(42):30845-55
17675291
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11724-9
16864775
J Biol Chem. 2008 Mar 28;283(13):8258-65
18195019
Methods Enzymol. 2002;350:87-96
12073338
J Biol Chem. 2007 Oct 19;282(42):30562-9
17726007
J Biol Chem. 1989 Dec 25;264(36):21652-9
2513324
Biochem J. 2007 Aug 1;405(3):379-95
17623009
J Biol Chem. 2007 Nov 23;282(47):34288-98
17890783
Can J Biochem Physiol. 1959 Aug;37(8):911-7
13671378
J Biol Chem. 2008 Jul 4;283(27):19049-57
18458083
J Biol Chem. 2004 Dec 31;279(53):55866-74
15485873
J Biol Chem. 2006 Apr 14;281(15):10134-42
16495221
J Biol Chem. 2006 Jul 21;281(29):20140-7
16704971
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2830-5
18287005
Prog Lipid Res. 2006 Nov;45(6):487-510
16814865
Proc Int Conf Intell Syst Mol Biol. 1998;6:175-82
9783223
J Biol Chem. 2002 Mar 15;277(11):8877-81
11751875
Mol Biol Cell. 2006 Jun;17(6):2636-45
16597698
J Biol Chem. 2007 Mar 2;282(9):6532-9
17182612
J Biol Chem. 2007 Dec 21;282(51):36853-61
17951629
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):88-93
18156367
Mol Cell Proteomics. 2005 Sep;4(9):1319-27
15965266
J Biol Chem. 1998 Oct 9;273(41):26765-71
9756920
J Mol Biol. 2001 Jan 19;305(3):567-80
11152613
Mol Biol Cell. 2008 Mar;19(3):1174-84
18094042
Science. 1999 Aug 6;285(5429):901-6
10436161
J Biol Chem. 1986 Jun 15;261(17):7771-7
3086318
FEBS Lett. 2007 Nov 27;581(28):5511-6
17996202
J Biol Chem. 2007 Sep 28;282(39):28344-28352
17652094
J Biol Chem. 1960 Aug;235:2233-7
14413818
FEBS Lett. 1973 Feb 15;30(1):29-34
11947055