Cloning and characterization of murine 1-acyl-<i>sn</i>-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart

Lü, Biao; Jiang, Yan; Zhou, Yingshan; Xu, Fred Y.; Hatch, Grant M.; Choy, Patrick C.

doi:10.1042/bj20041348

Cited by 104 publications

(101 citation statements)

References 46 publications

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“…Previous attempts for its isolation suggested that protein(s) of an apparent molecular mass of 50-60 kDa could be labeled with a photoreactive azido-lysoPC derivative in a partially purified microsomal fraction containing a LPCAT activity (10). To identify candidate LPCATs in RBCs, we searched databases for proteins carrying the E. coli plsC domain, which is characteristic of all known 1-acyl-sn-glycerol-3-phosphate acyltransferases (11)(12)(13), and excluded all known enzymes that have been described as lysophosphatidic acid acyltransferases (LPAATs). We focused particularly on two gene products of unknown function with a predicted molecular mass of 60 kDa, annotated in human as AYTL1 and AYTL2 and as Aytl1 and Aytl2 in mouse (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Five proteins have been identified in human and mouse containing the so-called plsC domain of the E. coli PlsC protein and have been reported to acylate lysoPA in the presence of acyl-CoA (12,13). However, systematic annotation of any plsC-containing protein homologous to AGPAT as an additional member of this family has led to some confusion, because not all appear to use lysoPA as substrate.…”

Section: Discussionmentioning

confidence: 99%

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Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Soupène¹,

Fyrst²,

Kuypers³

2008

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

105

107

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The mammalian RBC lacks de novo lipid synthesis but maintains its membrane composition by rapid turnover of acyl moieties at the sn-2 position of phospholipids. Plasma-derived fatty acids are esterified to acyl-CoA by acyl-CoA synthetases and transferred to lysophospholipids by acyl-CoA:lysophospholipid acyltransferases. We report the characterization of three lysophosphatidylcholine (lysoPC) acyltransferases (LPCATs), products of the AYTL1, -2, and -3 genes. These proteins are three members of a LPCAT family, of which all three genes are expressed in an erythroleukemic cell line. Aytl2 mRNA was detected in mouse reticulocytes, and the presence of the product of the human ortholog was confirmed in adult human RBCs. The three murine Aytl proteins generated phosphatidylcholine from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes. Spliced variants of Aytl1, affecting a conserved catalytic motif, were identified. Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus. Characterization of the product of the Aytl2 gene as the phosphatidylcholine reacylating enzyme in RBCs represents the identification of a plasma membrane lysophospholipid acyltransferase and establishes the function of a LPCAT protein.phosphatidylcholine ͉ RBC ͉ AYTL2

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Soupène¹,

Fyrst²,

Kuypers³

2008

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

105

107

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“…In vitro studies have revealed that liver fatty-acid binding protein can transport 1-acyl glycerol-3-phosphate from the mitochondria to target microsomes [13]. However, whether fatty-acid binding protein serves as a transporter in vivo remains elusive.Based on their known homology to mtGPAT, other acyltransferases for TAG synthesis in the Kennedy pathway were subsequently identified and studied, including AGPAT, DGAT and their isoforms [18,[22][23][24][25][26][27]. To date, eight AGPAT genes have been identified, although the physiological functions of each are not well established [28,29].…”

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confidence: 99%

Triacylglycerol Metabolism In Adipose Tissue

et al. 2007

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Triacylglycerol (TAG) in adipose tissue serves as the major energy storage form in higher eukaryotes. Obesity, resulting from excess white adipose tissue, has increased dramatically in recent years resulting in a serious public health problem. Understanding of adipocyte-specific TAG synthesis and hydrolysis is critical to the development of strategies to treat and prevent obesity and its closely associated diseases, for example, Type 2 diabetes, hypertension and atherosclerosis. In this review, we present an overview of the major enzymes in TAG synthesis and lipolysis, including the recent discovery of a novel adipocyte TAG hydrolase. Keywords1-acylglycerol-3-phosphate acyltransferase; desnutrin/adipose triglyceride lipase; diacylglycerol acyltransferase; glycerol-3-phosphate acyltransferase; hormone-sensitive lipase; lipolysis; phosphatidic acid phosphatase; triacylglycerol White adipose tissue (WAT) is the major energy reserve in higher eukaryotes. The primary purposes of WAT are synthesis and storage of triacylglycerol (TAG) in periods of energy excess, and hydrolysis of TAG to generate fatty acids for use by other organs during periods of energy deprivation [1]. Adipose tissue also secretes adipokines that regulate energy intake and metabolism.The prevalence of obesity resulting from excess WAT has increased dramatically in recent years resulting in a serious public health problem, since obesity is closely associated with a number of disorders including Type 2 diabetes, hypertension and atherosclerosis [2]. While † Author for correspondence, University of California, Department of Nutritional Sciences & Toxicology, Berkeley, CA 94720, USA, adipocyte number has been shown to increase (hyperplasia) in morbid obesity, obesity is primarily attributed to adipocyte hypertrophy that occurs when TAG synthesis (esterification) exceeds TAG breakdown (lipolysis), resulting in elevated TAG storage [1]. Although it has been postulated that large adipocyte size may contribute to insulin resistance, the molecular mechanism is not clear.Paradoxically, the metabolic abnormalities typically found in obesity are also associated with lipodystrophies that are characterized by selective loss of adipose tissue from particular regions of the body [3][4][5][6]. Although the underlying molecular mechanisms are not clear, metabolic complications may result from ectopic storage of TAG in tissues such as the liver and muscle [7][8][9]. A proper capacity for TAG storage in adipocytes is clearly important for normal metabolic regulation. In view of the wide range of health problems associated with improper fat storage and release, it is critical to understand adipocyte-specific regulation of TAG synthesis and hydrolysis. Biosynthesis of triacylglycerolThe synthesis of phosphatidic acid and its subsequent conversion to TAG was described more than 40 years ago by Kennedy and coworkers [10], and is summarized in Figure 1. The initial committal step in this pathway is the formation of lysophosphatidic acid (1-acylglycerol-3-phosphate)...

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“…Structural analysis of several glycerolipid acyltransferases from a variety of organisms has revealed a critical domain responsible for their catalytic activity (12). The critical amino acid motif of H(X) 4 D is present within this domain in all glycerolipid acyltransferases that have been studied to date (8)(9)(10)(11). To our knowledge, the cloning of any lysoPC acyltransferase has not been reported.…”

mentioning

confidence: 99%

“…Only a few glycerol lipid acyltransferases have been cloned and sequenced (7)(8)(9)(10)(11). Structural analysis of several glycerolipid acyltransferases from a variety of organisms has revealed a critical domain responsible for their catalytic activity (12).…”

mentioning

confidence: 99%

Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells

Chen

Hyatt

Mucenski

et al. 2006

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

175

187

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Pulmonary surfactant is a complex of lipids and proteins produced and secreted by alveolar type II cells that provides the low surface tension at the air-liquid interface. The phospholipid most responsible for providing the low surface tension in the lung is dipalmitoylphosphatidylcholine. Dipalmitoylphosphatidylcholine is synthesized in large part by phosphatidylcholine (PC) remodeling, and a lysophosphatidylcholine (lysoPC) acyltransferase is thought to play a critical role in its synthesis. However, this acyltransferase has not yet been identified. We have cloned full-length rat and mouse cDNAs coding for a lysoPC acyltransferase (LPCAT). LPCAT encodes a 535-aa protein of Ϸ59 kDa that contains a transmembrane domain and a putative acyltransferase domain. When transfected into COS-7 cells and HEK293 cells, LPCAT significantly increased lysoPC acyltransferase activity. LPCAT preferred lysoPC as a substrate over lysoPA, lysoPI, lysoPS, lysoPE, or lysoPG and prefers palmitoyl-CoA to oleoyl-CoA as the acyl donor. This LPCAT was preferentially expressed in the lung, specifically within alveolar type II cells. Expression in the fetal lung and in rat type II cells correlated with the expression of the surfactant proteins. LPCAT expression in fetal lung explants was sensitive to dexamethasone and FGFs. KGF was a potent stimulator of LPCAT expression in cultured adult type II cells. We hypothesize that LPCAT plays a critical role in regulating surfactant phospholipid biosynthesis and suggest that understanding the regulation of LPCAT will offer important insight into surfactant phospholipid biosynthesis.biochemistry ͉ lung ͉ surfactant ͉ phosphatidylcholine

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Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart

Cited by 104 publications

References 46 publications

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Triacylglycerol Metabolism In Adipose Tissue

Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells

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