Member of the membrane-bound O-acyltransferase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity.
Glycerophospholipids in biological membranes are metabolically active and participate in a series of deacylation-reacylation reactions, which may lead to accumulation of polyunsaturated fatty acids (PUFAs) at the sn-2 position of the glycerol backbone. The reacylation reaction is believed to be catalyzed by acyl-coenzyme A (acyl-CoA):lysophospholipid acyltransferase. Very recently, we have shown that Caenorhabditis elegans mboa-7, which belongs to the membrane-bound O-acyltransferase (MBOAT) family, encodes lysophosphatidylinositol (LPI)-specific acyltransferase (LPIAT). In this study, we found that knockdown of another member of the MBOAT family in C. elegans, named mboa-6, reduced incorporation of exogenous PUFAs into phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE) in C. elegans. Knockdown of a human mboa-6 homologue, referred to as MBOAT5, also impaired the incorporation of PUFAs into PC, PS and PE in HeLa cells. In in vitro assays, lysoPC (LPC), lysoPS (LPS) and lysoPE (LPE) acyltransferase activities using [(14)C]arachidonoyl-CoA were significantly reduced in the microsomes of MBOAT5 knockdown cells. Conversely, over-expression of MBOAT5 in human embryonic kidney (HEK) 293 cells resulted in great increases in LPC, LPS and LPE acyltransferase activities but not in LPIAT or lysophosphatidic acid (LPA) acyltransferase (LPAAT) activities. These results indicate that human MBOAT5 is a lysophospholipid acyltransferase acting preferentially on LPC, LPS and LPE.
Matsuda
Shinji
S
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Inoue
Takao
T
Lee
Hyeon-Cheol
HC
Kono
Nozomu
N
Tanaka
Fumiharu
F
Gengyo-Ando
Keiko
K
Mitani
Shohei
S
Arai
Hiroyuki
H
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013379:Substrate Specificity
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; C008301:lysophosphatidylethanolamine; C025059:lysophosphatidylserine; D008243:1-Acylglycerophosphocholine O-Acyltransferase