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evolution
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the LPCAT genes are highly conserved, suggesting that the duplicated LPCAT genes were derived from a segmental duplication event. The segmental duplication is the result of a recent whole-genome duplication event in flax
evolution
enzyme At1g78690 shares high homology (about 40%) with the cardiolipin remodeling enzyme tafazzin, but the cardiolipin remodeling enzyme tafazzin and the lysophospholipid acyltransferase catalyze unique reactions
evolution
LPLATs have been identified in the membrane-bound O-acyltransferase (MBOAT) and 1-acyl-glycerol-3-phosphate O-acyltransferase families. Lysophosphatidylcholine acyltransferases (LPCATs), including isozymes LPCAT1-4, have LPLAT activities other than LPCAT activity. For example, LPCAT4 has lysophosphatidylethanolamine acyltransferase as well as LPCAT activity
evolution
the enzyme belongs to the MBOAT family
malfunction
LPCAT3 knockdown induces a spindle-shaped morphology typical of M1-polarized macrophages, increases the secretion of CXCL10, and decreases the levels of CD206 in interleukin-4-activated U-937 cells. Knockdown of LPCAT3 shifts the differentiation of phorbol ester-treated U-937 cells to M1-polarized macrophages. Decrease in the content of phosphatidylcholine containing linoleic acid or arachidonic acid in biological membranes caused by the suppression of LPCAT3 may influencemembrane fluidity, curvature and function
malfunction
the liver X receptor-mediated effects on arachidonic acid distribution are abolished by LPCAT3 silencing, and a redistribution of arachidonic acid toward the neutral lipid fraction is observed
malfunction
despite di-acylate phosphatidylglycerol being a substrate, overexpression of At1g78690 in Escherichia coli leads to the accumulation of acyl-PG. Cardiolipin also accumulates in cells overexpressing At1g78690, cardiolipin is found in the inner mitochondrial membrane in eukaryotes and is critical for mitochondrial function. It serves as a necessary proton trap for oxidative phosphorylation and is a trigger for apoptosis
malfunction
LPCAT1 gene-trapped mice show decreased lung saturated phosphatidylcholine and higher perinatal mortality due to respiratory failure. LPCAT1-KO mice also show decreased lung dipalmitoyl-PC and blood oxygenation levels, and lower survival ratios compared to wild-type mice in a ventilator-induced lung injury model, which is an acute lung inflammatory model. Retinal degeneration and defects in visual function are also reported in a mouse strain containing a mutation in LPCAT1, rd11, reduced retinal dipalmitoyl-PC contents in mutant mice, reproducing the similar observation in the lung
malfunction
LPCAT1 gene-trapped mice show decreased lung saturated phosphatidylcholine and higher perinatal mortality due to respiratory failure. LPCAT1-KO mice also show decreased lung dipalmitoyl-PC and blood oxygenation levels, and lower survival ratios compared to wild-type mice in a ventilator-induced lung injury model, which is an acute lung inflammatory model. Retinal degeneration and defects in visual function are also reported in a mouse strain containing a mutation in LPCAT1, reduced retinal dipalmitoyl-PC contents in mutant mice, reproducing the similar observation in the lung
malfunction
LPCAT1 knockdown enhances polyunsaturated fatty acids (PUFAs)-induced cytotoxicity. In LPCAT1 knockout mice, DPPC level is reduced and UPR is activated in the retina. In a study of rd11 mice in which there is a natural loss-of-function of LPCAT1, the level of DPPC in the retina is decreased, resulting in retinal degeneration
malfunction
LPCAT1 knockdown enhances polyunsaturated fatty acids (PUFAs)-induced cytotoxicity. Transfection of an siRNA against LPCAT1 efficiently reduces protein expression of LPCAT1 in HeLa cells. LPCAT1 knockdown cells show a significant reduction in the amount of DPPC upon eicosapentaenoic acid (EPA; 20:5) treatment compared with siControl-transfected cells, whereas the amounts of EPA-containing species are not affected by LPCAT1 knockdown. Oleic acid treatment has no effect
malfunction
LPCAT3 deficiency decreases arachidonic acid containing PC, PE, and PS and induces neonatal lethality due to triacylglycerol (TG) accumulation and dysfunction in enterocytes. LPCAT3-KO mice show longer and bigger small intestine. In response to high-fat feeding, LPCAT3 deficiency in the intestine increases a gut hormone, GLP-1, and oleoylethanolamide. These results suggest that AA-containing PC is a key molecule in regulating dietary lipid absorption. LPCAT3 deficiency reduces cholesterol efflux in macrophages and intestine. Excess cellular cholesterol by LPCAT3 deficiency increases intestinal stem cell proliferation and promotes tumorigenesis
malfunction
LPCAT4 knockdown decreases mRNA and protein levels of chondrogenic markers as well as Alcian blue staining intensity and alkaline phosphatase activity in ATDC5 cells. Knockdown of LPCAT4 suppresses the mRNA levels of chondrogenic differentiation markers, Col10, alkaline phosphatase (ALP), aggrecan, and transforming growth factor-beta (TGF-beta) and protein expression of Col10. LPCAT4 plays important roles during the transition of chondrocytes into hypertrophic chondrocytes and/or a mineralized phenotype. LPCAT4 knockdown inhibits hypertrophy/mineralization after a chondrogenic phenotype has been attained in ATDC5 cells
malfunction
Neuro 2A cells overexpressing LPEAT2 underwent cell death with necrotic morphology when differentiated into neuron-like cells, with supplementation with 22:6 (DHA)
malfunction
transient liver-specific knockdown of LPCAT3 in mice affects PPARdelta-mediated activation of several hepatic genes involving in fatty acid metabolism. Mice lacking LPCAT3 in the liver show reduced plasma triglycerides and hepatosteatosis and secrete lipid-poor VLDL lacking arachidonoyl phospholipids
malfunction
upon hepatitis C virus (HCV) infection, both Huh-7.5.1 cells and primary human hepatocytes (PHH) show decreased levels of LPCAT1 transcript and protein, consistent with transcriptional downregulation. LPCAT1 depletion in either naive or infected Huh-7.5.1 cells results in altered lipid metabolism characterised by lipid droplet remodelling, increased triacylglycerol storage, and increased secretion of VLDL. In infected Huh-7.5.1 cells or PHH, LPCAT1 depletion increases production of the viral particles of lowest density and highest infectivity
metabolism
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key enzyme in platelet-activating factor biosynthesis
metabolism
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the enzyme is involved in the Kennedy pathway for triacylglycerol synthesis, biochemical coupling of isozyme LPCAT1 and the diacylglycerol acyltransferase DGAT1-1-catalyzed reactions, overview. Both enzymes are required for synthesis of triacylgycerol
metabolism
the liver X receptor-mediated induction of enzyme LPCAT3 specifically regulates the metabolism of arachidonic acid, the precursor of key inflammatory mediators, such as eicosanoids. Liver X receptor and lysophosphatidylcholine acyltransferase 3 modulate the fatty acid composition of human macrophages, overview
metabolism
phospholipase A2 (PLA2) plays a role in membrane phospholipid remodeling by coupling with re-acylation processes mediated by lysophospholipid acyltransferases (LPLATs) to generate sn-1/sn-2 fatty acid asymmetry of phospholipids. Lysophospholipids are acylated by LPLAT to generate phospholipids phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), and cardiolipin (CL) by LPLATs. In the Kennedy pathway, glycerol-3-phosphate (G3P) is first acylated by glycerol-phosphate acyltransferase (GPAT) to form lyso-PA (LPA), which is subsequently converted to PA by LPA-acyltransferase (LPAAT)
metabolism
phospholipase A2 (PLA2) plays a role in membrane phospholipid remodeling by coupling with re-acylation processes mediated by lysophospholipid acyltransferases (LPLATs) to generate sn-1/sn-2 fatty acid asymmetry of phospholipids. Lysophospholipids are acylated by LPLAT to generate phospholipids phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), and cardiolipin (CL) by LPLATs. In the Kennedy pathway, glycerol-3-phosphate (G3P) is first acylated by glycerol-phosphate acyltransferase (GPAT) to form lyso-PA (LPA), which is subsequently converted to PA by LPA-acyltransferase (LPAAT). Dipalmitoyl-PC is biosynthesized by LPCAT1 in the Lands' cycle
metabolism
phospholipase A2 (PLA2) plays a role in membrane phospholipid remodeling by coupling with re-acylation processes mediated by lysophospholipid acyltransferases (LPLATs) to generate sn-1/sn-2 fatty acid asymmetry of phospholipids. Lysophospholipids are acylated by LPLAT to generate phospholipids phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), and cardiolipin (CL) by LPLATs. In the Kennedy pathway, glycerol-3-phosphate (G3P) is first acylated by glycerol-phosphate acyltransferase (GPAT) to form lyso-PA (LPA), which is subsequently converted to PA by LPA-acyltransferase (LPAAT). PAF is a potent phospholipid mediator that is biosynthesized by lyso-PAF acetyltransferase using lyso-PAF and acetyl-CoA
physiological function
double knockdown of both isoforms LPCAT1 and LPCAT2 in A-431 cells leads to strong reduction of lipid-droplet-associated enzymic activity
physiological function
double knockdown of both isoforms LPCAT1 and LPCAT2 in A-431 cells or single knockdown of isoform LPCAT1 in Hu-H7 cells leads to strong reduction of lipid-droplet-associated enzymic activity. Reduction of LPCAT1 activity in Hu-H7 cells is associated with a morphological alteration in the lipid droplet pool, the mean lipid droplet size increases, although the amount of stored triacylglycerols remains constant
physiological function
generation of mice bearing a hypomorphic allele of isoform Lpcat1. Newborn Lpcat1 hypomorphic mice show varying perinatal mortality from respiratory failure, with affected animals demonstrating hallmarks of respiratory distress such as atelectasis and hyaline membranes. Lpcat1 mRNA levels are reduced in newborn Lpcat1 hypomorphic mice and directly correlate with saturated phosphatidylcholine content, LPCAT1 activity, and survival. Surfactant isolated from dead Lpcat1 hypomorphic mice fails to reduce minimum surface tension to wild-type levels. Full LPCAT1 activity is required to achieve the levels of saturated phosphatidylcholine essential for the transition to air breathing
physiological function
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histone H4 protein is subject to palmitoylation catalyzed by Lpcat1 in a calcium-regulated manner. Cytosolic Lpcat1 shifts into the nucleus in lung epithelia in response to exogenous Ca2+. Nuclear Lpcat1 colocalizes with and binds to histone H4, where it catalyzes histone H4 palmitoylation. Residue Ser47 within histone H4 serves as a putative acceptor site, indicative of Lpcat1-mediated O-palmitoylation. Lpcat1 knock-down or expression of a histone H4 Ser47A mutant protein in cells decrease cellular mRNA synthesis
physiological function
in a diacylglycerol acyltransferase 1/diacylglycerol acyltransferase 2/phospholipid:diacylglycerol acyltransferase triple mutant the total lipid% dry cell weight as a percentage of the wild-type strain is 13%
physiological function
lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty acid composition in biological membranes. Lysophosphatidylcholine acyltransferases (LPCATs) are members of the LPLATs that play a role in inflammatory responses. LPCAT3 is reported to be a major contributor to increase polyunsaturated fatty acids, including linoleic acid and arachidonic acid, and is associated with inflammatory responses in human primary macrophages, and the enzyme LPCAT3 plays an important role in M1/M2-macrophage polarization, analysis of the underlying mechanism
physiological function
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phosphatidylcholine is the major site for polyunsaturated fatty acid synthesis. Enzyme lysophosphatidylcholine acyltransferase can transfer polyunsaturated fatty acids on phosphatidylcholine directly into the acyl-CoA pool, making these polyunsaturated fatty acids available for the diacylglycerol acyltransferase (DGAT)-catalyzed reaction for triacylglycerol production, proposed mechanism, overview
physiological function
pulmonary surfactant, a mixture of proteins and phospholipids, plays an important role in facilitating gas exchange by maintaining alveolar stability. Saturated phosphatidylcholine, the major component of surfactant, is synthesized both de novo and by the remodeling of unsaturated phosphatidylcholine by lyso-PC acyltransferase 1 (LPCAT1). After synthesis in the endoplasmic reticulum, saturated phosphatidylcholine is routed to lamellar bodies for storage prior to secretion. The enzyme forms a transient complex with saturated phosphatidylcholine and specific phospholipid transport protein(s) to initiate trafficking of saturated phosphatidylcholine from the endoplasmic reticulum to the lamellar bodies
physiological function
the enzyme is involved in the Lands cycle, it controls the fatty acid composition at the sn-2 position of glycerophospholipids and the availability of fatty acids, such as arachidonic acid, used for eicosanoid synthesis. LPCAT3 gene expression is regulated by liver X receptor in human primary macrophages and monocytes. Liver X receptor stimulation significantly enhances the lysophospholipid acyltransferase activity of LPCAT3 increasing the arachidonic acid content in the polar lipid fraction, specifically in phosphatidylcholines. Preconditioning of human macrophages by LXR agonist treatment increases the release of arachidonate-derived eicosanoids, such as prostaglandin E2 and thromboxane after lipopolysaccharide stimulation, with a significant attenuation by LPCAT3 silencing
physiological function
fatty acyl chains of membrane phospholipids are regulated by various lysophospholipid acyltransferases (LPLATs). Cells respond to loading with excess polyunsaturated fatty acids (PUFAs), such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. Dipalmitoylphosphatidylcholine (DPPC) is increased after the production of PUFA-containing phospholipids in cells loaded with PUFAs. An RNA interference screen of lipid-metabolizing enzymes reveals that lysophosphatidylcholine acyltransferase 1 (LPCAT1) is involved in the DPPC production, overview. Dipalmitoylphosphatidylcholine (DPPC) is produced via LPCAT1 to protect against excess PUFA-induced cytotoxicity
physiological function
fatty acyl chains of membrane phospholipids are regulated by various lysophospholipid acyltransferases (LPLATs). Cells respond to loading with excess polyunsaturated fatty acids (PUFAs), such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. Dipalmitoylphosphatidylcholine (DPPC) is increased after the production of PUFA-containing phospholipids in cells loaded with PUFAs. In murine retina, in which PUFAs are highly enriched, DPPC is produced along with increase of PUFA-containing phospholipids. Dipalmitoylphosphatidylcholine (DPPC) is produced via LPCAT1 to protect against excess PUFA-induced cytotoxicity
physiological function
glycerophospholipids have important structural and functional roles in cells and are the main components of cellular membranes. Glycerophospholipids are formed via the de novo pathway (Kennedy pathway) and are subsequently matured in the remodeling pathway (Lands' cycle). Lands' cycle consists of two steps: deacylation of phospholipids by phospholipases A2 and reacylation of lysophospholipids by lysophospholipid acyltransferases (LPLATs). LPLATs play key roles in the maturation and maintenance of the fatty acid composition of biomembranes, and cell differentiation. Lysophosphatidylcholine acyltransferase 4 is involved in chondrogenic differentiation of ATDC5 cells into chondrocytes. Lysophosphatidylcholine acyltransferase 4 (LPCAT4) mRNA expression and LPCAT enzymatic activity towards oleoyl-, linoleoyl-, (5Z,8Z,11Z,14Z)-eicosatetraenoyl-, and docosahexaenoyl-CoA increases in the late stage of chondrogenic differentiation, when mineralization occurs. Lysophosphatidylcholine (LPC) is involved in the pathogenesis of various lung disorders, including acute respiratory distress syndrom
physiological function
hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) has critical functions in triglycerides transport and endoplasmic reticulum stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Hepatic lysophosphatidylcholine acyltransferase 3 is encoded by a target gene regulated by peroxisome proliferator-activated receptor delta
physiological function
hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) has critical functions in triglycerides transport and endoplasmic reticulum stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Hepatic lysophosphatidylcholine acyltransferase 3 is encoded by a target gene regulated by peroxisome proliferator-activated receptor delta
physiological function
lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6, Prdx6, that shows a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction. The enzyme is a peroxiredoxin-6 (EC 1.11.1.27). Prdx6 also has a phospholipase A 2 (PLA2, EC 3.1.1.4) activity that plays important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. A linear incorporation of labeled fatty acyl CoA into dipalmitoyl phosphatidylcholine (PC) indicated that lysophosphatidylcholine generated by Prdx6 PLA2 activity remains bound to the enzyme for the reacylation reaction. Prdx6 is a complete enzyme comprising both PLA2 and LPCAT activities for the remodeling pathway of PC synthesis or for repair of membrane lipid peroxidation. The remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane
physiological function
lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6, Prdx6, that shows a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction. The enzyme is a peroxiredoxin-6 (EC 1.11.1.27). Prdx6 also has a phospholipase A 2 (PLA2, EC 3.1.1.4) activity that plays important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. A linear incorporation of labeled fatty acyl CoA into dipalmitoyl phosphatidylcholine (PC) indicated that lysophosphatidylcholine generated by Prdx6 PLA2 activity remains bound to the enzyme for the reacylation reaction. Prdx6 is a complete enzyme comprising both PLA2 and LPCAT activities for the remodeling pathway of PC synthesis or for repair of membrane lipid peroxidation. The remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane
physiological function
lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6, Prdx6, that shows a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction. The enzyme is a peroxiredoxin-6 (EC 1.11.1.27). Prdx6 also has a phospholipase A 2 (PLA2, EC 3.1.1.4) activity that plays important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. A linear incorporation of labeled fatty acyl CoA into dipalmitoyl phosphatidylcholine (PC) indicates that lysophosphatidylcholine generated by Prdx6 PLA2 activity remains bound to the enzyme for the reacylation reaction. Prdx6 is a complete enzyme comprising both PLA2 and LPCAT activities for the remodeling pathway of PC synthesis or for repair of membrane lipid peroxidation. The remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane
physiological function
lysophosphatidylcholine acyltransferase 1 (LPCAT1), as an LD phospholipid-remodelling enzyme, plays a role in liver lipid metabolism and HCV infectious cycle
physiological function
lysophosphatidylcholine acyltransferase 3 (LPCAT3) is an important enzyme in phospholipid remodeling, a process that influences the biophysical properties of cell membranes and thus cell function. LPCAT3 is involved in several diseases, including atherosclerosis, non-alcoholic steatohepatitis, and carcinoma
physiological function
lysophosphatidylethanolamine acyltransferase 2 (LPEAT2), one of the enzymes that play a role in the remodeling pathway, has been reported to have lysophosphatidylcholine acyltransferase (LPCAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities with 16:0-CoA, 18:0-CoA, and 18:1-CoA as donors. LPEAT2 incorporates docosahexanoic acid (DHA) into phospholipids and has possible functions for fatty acid-induced cell death. LPEAT2 shows endogenous LPEAT activity with 22:6-CoA, and functions in modulating 22:6/20:4 ratios of phospholipids. LPEAT2 plays a role in inducing cell death DHA-dependently. Cell death induced by DHA is dependent on mLPEAT2, insights on mechanisms of neuronal necrosis
physiological function
role for LPCAT1 in respiratory function: the production of surfactant phospholipids
physiological function
role for LPCAT3 in lipid and energy homeostasis
physiological function
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pulmonary surfactant, a mixture of proteins and phospholipids, plays an important role in facilitating gas exchange by maintaining alveolar stability. Saturated phosphatidylcholine, the major component of surfactant, is synthesized both de novo and by the remodeling of unsaturated phosphatidylcholine by lyso-PC acyltransferase 1 (LPCAT1). After synthesis in the endoplasmic reticulum, saturated phosphatidylcholine is routed to lamellar bodies for storage prior to secretion. The enzyme forms a transient complex with saturated phosphatidylcholine and specific phospholipid transport protein(s) to initiate trafficking of saturated phosphatidylcholine from the endoplasmic reticulum to the lamellar bodies
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physiological function
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in a diacylglycerol acyltransferase 1/diacylglycerol acyltransferase 2/phospholipid:diacylglycerol acyltransferase triple mutant the total lipid% dry cell weight as a percentage of the wild-type strain is 13%
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physiological function
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lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6, Prdx6, that shows a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction. The enzyme is a peroxiredoxin-6 (EC 1.11.1.27). Prdx6 also has a phospholipase A 2 (PLA2, EC 3.1.1.4) activity that plays important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. A linear incorporation of labeled fatty acyl CoA into dipalmitoyl phosphatidylcholine (PC) indicates that lysophosphatidylcholine generated by Prdx6 PLA2 activity remains bound to the enzyme for the reacylation reaction. Prdx6 is a complete enzyme comprising both PLA2 and LPCAT activities for the remodeling pathway of PC synthesis or for repair of membrane lipid peroxidation. The remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane
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additional information
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the specific activity of flax LPCAT1-catalyzed forward reaction is about 1000 times higher than that of flax DGAT1-catalyzed reaction when the coexpressed recombinant enzymes are assessed in yeast microsomes under in vitro enzyme assays, overview
additional information
a constitutive type of lyso-PAF acetyltransferase enzyme
additional information
a constitutive type of lyso-PAF acetyltransferase enzyme
additional information
a constitutive type of lyso-PAF acetyltransferase enzyme
additional information
amino acid D31 is crucial for LPCAT activity
additional information
amino acid D31 is crucial for LPCAT activity
additional information
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amino acid D31 is crucial for LPCAT activity
additional information
an inducible type of lyso-PAF acetyltransferase enzyme
additional information
an inducible type of lyso-PAF acetyltransferase enzyme
additional information
an inducible type of lyso-PAF acetyltransferase enzyme
additional information
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lipid extraction and analysis from the seeds of Camelina sativa
additional information
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amino acid D31 is crucial for LPCAT activity
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