LPGAT1 controls the stearate/palmitate ratio of phosphatidylethanolamine and phosphatidylcholine in sn-1 specific remodeling.

Autor:	Xu Y; Department of Anesthesiology, New York University Grossman School of Medicine, New York, New York, USA., Miller PC; Department of Pediatrics, New York University Grossman School of Medicine, New York, New York, USA., Phoon CKL; Department of Pediatrics, New York University Grossman School of Medicine, New York, New York, USA., Ren M; Department of Anesthesiology, New York University Grossman School of Medicine, New York, New York, USA; Department of Cell Biology, New York University Grossman School of Medicine, New York, New York, USA., Nargis T; Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, New York, USA., Rajan S; Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, New York, USA., Hussain MM; Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, New York, USA., Schlame M; Department of Anesthesiology, New York University Grossman School of Medicine, New York, New York, USA; Department of Cell Biology, New York University Grossman School of Medicine, New York, New York, USA. Electronic address: michael.schlame@med.nyu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2022 Mar; Vol. 298 (3), pp. 101685. Date of Electronic Publication: 2022 Feb 04.
DOI:	10.1016/j.jbc.2022.101685
Abstrakt:	Most mammalian phospholipids contain a saturated fatty acid at the sn-1 carbon atom and an unsaturated fatty acid at the sn-2 carbon atom of the glycerol backbone group. While the sn-2 linked chains undergo extensive remodeling by deacylation and reacylation (Lands cycle), it is not known how the composition of saturated fatty acids is controlled at the sn-1 position. Here, we demonstrate that lysophosphatidylglycerol acyltransferase 1 (LPGAT1) is an sn-1 specific acyltransferase that controls the stearate/palmitate ratio of phosphatidylethanolamine (PE) and phosphatidylcholine. Bacterially expressed murine LPGAT1 transferred saturated acyl-CoAs specifically into the sn-1 position of lysophosphatidylethanolamine (LPE) rather than lysophosphatidylglycerol and preferred stearoyl-CoA over palmitoyl-CoA as the substrate. In addition, genetic ablation of LPGAT1 in mice abolished 1-LPE:stearoyl-CoA acyltransferase activity and caused a shift from stearate to palmitate species in PE, dimethyl-PE, and phosphatidylcholine. Lysophosphatidylglycerol acyltransferase 1 KO mice were leaner and had a shorter life span than their littermate controls. Finally, we show that total lipid synthesis was reduced in isolated hepatocytes of LPGAT1 knockout mice. Thus, we conclude that LPGAT1 is an sn-1 specific LPE acyltransferase that controls the stearate/palmitate homeostasis of PE and the metabolites of the PE methylation pathway and that LPGAT1 plays a central role in the regulation of lipid biosynthesis with implications for body fat content and longevity. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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