Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms

Yamashita, Atsushi; Hayashi, Yasuhiko; Nemoto-Sasaki, Yoko; Ito, Makoto; Oka, Saori; Tanikawa, Takashi; Waku, Keizo; Sugiura, Takayuki

doi:10.1016/j.plipres.2013.10.001

Cited by 221 publications

(282 citation statements)

References 628 publications

Supporting

Mentioning

277

Contrasting

Unclassified

Order By: Relevance

“…AA undergoes a specific pattern of incorporation into PLs where initial acylation is primarily in PC and PI resulting from reactions catalyzed by ACSs and lyso-PLATs. Once AA is incorporated into PC species, it is then transferred primarily into 1-radyl PE species by a CoA-IT-catalyzed reaction (19)(20)(21)(22)(23)(24). Upon appropriate cell stimulation, AA can be hydrolyzed from PL by PLA 2 and can be converted by LOXs and COXs into many different bioactive lipid mediators, called eicosanoids, which include HETEs, leukotrienes, prostaglandins, and lipoxins (24)(25)(26)(27).…”

Section: Preparation and Stimulation Of Human Neutrophilsmentioning

confidence: 99%

On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid

Robichaud

Poirier

Boudreau

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

Section: Preparation and Stimulation Of Human Neutrophilsmentioning

confidence: 99%

On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid

Robichaud

Poirier

Boudreau

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

“…The facts that the PNPLA3-induced alterations in molecular species composition observed in TAGs, DAGs, and PCs were not present in PAs, and that the total cellular PA content was not signifi cantly altered, suggest that PNPLA3 may not signifi cantly modify lipid syntheses at the level of PA ( 17 ) ( 15 ). Acyl chain remodeling is considered a frequent process in hepatocytes, and in addition to acyltransferases, transacylases are present that catalyze the acyl chain transfer ( 32,33 ). Our cell model data employing acute overexpression of PNPLA3 reveals that PNPLA3 has the capacity to modify the TAG, DAG, and PC FA composition.…”

Section: Pnpla3mentioning

confidence: 99%

PNPLA3 mediates hepatocyte triacylglycerol remodeling

Ruhanen

Perttilä

Hölttä‐Vuori

et al. 2014

Journal of Lipid Research

101

View full text Add to dashboard Cite

a single-nucleotide polymorphism (rs738409; C>G/I148M) in the patatin-like phospholipase domain containing 3 ( PNPLA3 , adiponutrin) gene, to be strongly associated with NAFLD. A meta-analysis of 16 studies demonstrated that homozygous carriers of PNPLA3 I148M have on the average a 73% higher liver fat content than weight-matched homozygous carriers of the major allele ( 5 ). However, NAFLD associated with PNPLA3I148M is distinct from obesity-associated common NAFLD, as it is not characterized by features of the metabolic syndrome such as hyperinsulinemia or dyslipidemia ( 1, 5 ).In vitro assays using recombinant PNPLA3 have suggested that the WT PNPLA3 (PNPLA3 WT ) hydrolyzes emulsifi ed triacylglycerol (TAG) and that the I148M substitution in PNPLA3 (PNPLA3 I148M ) abolishes this activity ( 6-8 ). Moreover, the protein was shown to display a transacylase activity ( 7 ), and to prefer oleic acid (18:1n-9) as the fatty acyl moiety ( 9 ). Opposing a putative role as a lipase, PNPLA3 is induced by glucose and insulin ( 10-12 ) and is a target gene of the lipogenic transcription factors SREBP-1c and the carbohydrate responsive element binding protein, ChREBP ( 13-16 ). Kumari et al. ( 17 ) suggested that the protein acts as lipogenic lysophosphatidic acid (LPA) acyltransferase, converting LPA to phosphatidic acid (PA), and that the I148M substitution increases this activity. Because PA acts as a precursor for both phospholipids and TAGs, this provided an alternative explanation for the hepatic fat accumulation in the PNPLA3 I148M

show abstract

“…Once within the cell these PUFAs are very quickly remodeled into cellular phospholipids. For example, the remodeling of arachidonic acid by what has been termed the Lands cycle has been studied for a number of years (5) and is known to be responsible for the diversity of phospholipid molecular species seen in all cellular membranes. This phospholipid remodeling pathway is a result of CoA esters of PUFAs being synthesized by a family of long chain acyl CoA-synthases (ACSLs) (6) and the action of specific acyltransferases, including the lysophospholipid acyltransferases LPCAT3/MBOAT5 (7) and LPIAT1/MBOAT7 (8), known to incorporate arachidonic acid into phosphatidylcholine and phosphatidylinositol, respectively.…”

Section: Introductionmentioning

confidence: 99%