Recent progress on acyl CoA: lysophospholipid acyltransferase research

Shindou, Hideo; Hishikawa, Daisuke; Harayama, Takeshi; Yuki, Koichi; Shimizu, Takao

doi:10.1194/jlr.r800035-jlr200

Cited by 231 publications

(220 citation statements)

References 32 publications

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“…To date, four enzymes with LPCAT activity have been described in humans (45), LPCAT1, LPCAT2, and LPCAT4, members of the 1-acylglycerol-3-phosphate O-acyltransferase family, and LPCAT3, belonging to the membrane-bound O-acyltransferase family. In mouse, LPCAT2 (53) and LPCAT3 (49) have been suggested to show a preference for AA.…”

Section: Discussionmentioning

confidence: 99%

Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes

Pérez-Chacón

Astudillo²,

Ruipérez³

et al. 2009

The Journal of Immunology

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Cellular availability of free arachidonic acid (AA) is an important step in the production of pro- and anti-inflammatory eicosanoids. Control of free AA levels in cells is carried out by the action of phospholipase A2s and lysophospholipid acyltransferases, which are responsible for the reactions of deacylation and incorporation of AA from and into the sn-2 position of phospholipids, respectively. In this work, we have examined the pathways for AA incorporation into phospholipids in human monocytes stimulated by zymosan. Our data show that stimulated cells exhibit an enhanced incorporation of AA into phospholipids that is not secondary to an increased availability of lysophospholipid acceptors due to phospholipase A2 activation but rather reflects the receptor-regulated nature of the AA reacylation pathway. In vitro activity measurements indicate that the receptor-sensitive step of the AA reacylation pathway is the acyltransferase using lysophosphatidylcholine (lysoPC) as acceptor, and inhibition of the enzyme lysoPC acyltransferase 3 by specific small interfering RNA results in inhibition of the stimulated incorporation of AA into phospholipids. Collectively, these results define lysoPC acyltransferase 3 as a novel-signal–regulated enzyme that is centrally implicated in limiting free AA levels in activated cells.

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Section: Discussionmentioning

confidence: 99%

Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes

Pérez-Chacón

Astudillo²,

Ruipérez³

et al. 2009

The Journal of Immunology

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“…Because of its potential common occurrence in diverse human microbiomes, we elected to study this Cbeg in more detail. Cbeg12 is predicted to be a member of the acetyltransferase-5 family of enzymes, which is part of the lysophospholipid acyltransferase superfamily (PFAM CL0257) common to every domain of life (52). Enzymes from the acetytransferase-5 family are not known to produce commensal bacteria effectors, although acetyltransferase-5 enzymes from soil metagenomes are known to make N-acylated amino acids (15,20,21).…”

Section: Comparative Phylogenetic and Functional Analysis Of Effectormentioning

confidence: 99%

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

Cohen

Kang

Chu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

151

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The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about the specific effectors that commensal bacteria use to interact with the human host. Functional metagenomics provides a systematic means of surveying commensal DNA for genes that encode effector functions. Here, we examine 3,000 Mb of metagenomic DNA cloned from three phenotypically distinct patients for effectors that activate NF-κB, a transcription factor known to play a central role in mediating responses to environmental stimuli. This screen led to the identification of 26 unique commensal bacteria effector genes (Cbegs) that are predicted to encode proteins with diverse catabolic, anabolic, and ligand-binding functions and most frequently interact with either glycans or lipids. Detailed analysis of one effector gene family (Cbeg12) recovered from all three patient libraries found that it encodes for the production of N-acyl-3-hydroxypalmitoyl-glycine (commendamide). This metabolite was also found in culture broth from the commensal bacterium Bacteroides vulgatus, which harbors a gene highly similar to Cbeg12. Commendamide resembles long-chain N-acyl-amides that function as mammalian signaling molecules through activation of G-protein–coupled receptors (GPCRs), which led us to the observation that commendamide activates the GPCR G2A/GPR132. G2A has been implicated in disease models of autoimmunity and atherosclerosis. This study shows the utility of functional metagenomics for identifying potential mechanisms used by commensal bacteria for host interactions and outlines a functional metagenomics-based pipeline for the systematic identification of diverse commensal bacteria effectors that impact host cellular functions.

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“…Free FAs are activated by an acyl-CoA synthetase (ACSL) to produce the required acyl-CoA. Several PLA 2 s, LPLATs, and ACSLs having different characteristics and substrate specifi cities have been recently discovered, and their differential expression is likely responsible for the diversity of GPL molecular species in different tissues (5)(6)(7)(8)(9)(10)(11).…”

Section: Lymphocyte Isolation and Culturementioning

confidence: 99%

Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells

Robichaud

Boulay

Munganyiki

et al. 2013

Journal of Lipid Research

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Recent progress on acyl CoA: lysophospholipid acyltransferase research

Cited by 231 publications

References 32 publications

Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes

Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells

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