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Literature summary for 2.3.1.23 extracted from

  • Fisher, A.B.; Dodia, C.; Sorokina, E.M.; Li, H.; Zhou, S.; Raabe, T.; Feinstein, S.I.
    A novel lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6 (2016), J. Lipid Res., 57, 587-596 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene prdx6, functional recombinant enzyme expression in mouse pulmonary microvascular endothelial cells via infection with a lentiviral vector construct Mus musculus
gene prdx6, recombinant enzyme expression Homo sapiens
gene prdx6, recombinant enzyme expression Rattus norvegicus

Protein Variants

Protein Variants Comment Organism
C47S site-directed mutagenesis, construction of mutant endothelial cells via lentivirus transfection. The C47S mutant protein does not express peroxidase activity, but both PLA2 and LPCAT activities are preserved Mus musculus
D140A site-directed mutagenesis, construction of mutant endothelial cells via lentivirus transfection. The D140A mutant protein retains full peroxidase activity Mus musculus
D31A site-directed mutagenesis, construction of mutant endothelial cells via lentivirus transfection Homo sapiens
D31A site-directed mutagenesis, construction of mutant endothelial cells via lentivirus transfection, the mutant loses almost all LPCAT activity, but retains PLA2 activity Mus musculus
H26A site-directed mutagenesis, breeding of H26A Prdx6 knock-in mutant mice, the final targeting construct is linearized, sequence verified, and electroporated into C57Bl/6J ES cells (EAP6 ES cells) for insertion of the mutant sequences into the mouse genome by homologous recombination, positive clones are used for blastocyst injection into CD-1/BALB/c mice, chimeric H26A Prdx6 mice are bred to C57Bl/6J wild-type mice and the resulting heterozygotic mice are bred to homozygosity. The H26A mutant retains the ability to reduce short chain hydroperoxides, but cannot reduce phospholipid hydroperoxides, as they do not bind to the phospholipid substrate Mus musculus
H26A site-directed mutagenesis, construction of mutant endothelial cells via lentivirus transfection Homo sapiens
additional information construction of a LPCAT knockout mutant Mus musculus
S32A site-directed mutagenesis, the S32A mutant retains the ability to reduce short chain hydroperoxides, but cannot reduce phospholipid hydroperoxides, as they do not bind to the phospholipid substrate Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
CI-976 about 50% inhibition at 0.01 mM Homo sapiens
CI-976
-
Mus musculus
CI-976 about 50% inhibition at 0.01 mM Rattus norvegicus
additional information in wild-type lamellar bodies, markedly decreased incorporation of labeled palmitate into phosphatidylcholine is observed in the presence of MJ33, an inhibitor of the PLA2 activity of Prdx6 and, therefore, an inhibitor of LPC generation. This decreased incorporation of palmitate into PC in the presence of MJ33 is reversed by the addition of exogenous LPC to the LB incubation medium. Presence of CI-976 also markedly inhibits the incorporation of palmitoyl CoA into PC, but, unlike the results with MJ33, there is no change in the inhibition with addition of LPC Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm Prdx6 is a unique LPCAT enzyme with demonstrated cytoplasmic localization Homo sapiens 5737
-
cytoplasm Prdx6 is a unique LPCAT enzyme with demonstrated cytoplasmic localization Mus musculus 5737
-
cytoplasm Prdx6 is a unique LPCAT enzyme with demonstrated cytoplasmic localization Rattus norvegicus 5737
-
lamellar body
-
Homo sapiens 42599
-
lamellar body
-
Mus musculus 42599
-
lamellar body
-
Rattus norvegicus 42599
-
additional information the remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane Homo sapiens
-
-
additional information the remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane Mus musculus
-
-
additional information the remodeling pathway for the repair of peroxidized cell membranes presumably occurs at the cytoplasmic face of the affected cell membrane Rattus norvegicus
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mus musculus 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 ?
-
-
additional information Homo sapiens 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 ?
-
-
additional information Rattus norvegicus 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 ?
-
-
additional information Mus musculus C57BL/6J 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 ?
-
-
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine Homo sapiens
-
CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine Mus musculus
-
CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine Rattus norvegicus
-
CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine Mus musculus C57BL/6J
-
CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P30041
-
-
Mus musculus O08709
-
-
Mus musculus C57BL/6J O08709
-
-
Rattus norvegicus O35244
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein Prdx6 is phosphorylated at amino acid T177 by incubation with the MAPK, Erk 2, in the presence of Mg2+-ATP Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme hPrdx6 by anion exchange chromatography Homo sapiens
recombinant enzyme rPrdx6 by anion exchange chromatography Rattus norvegicus

Source Tissue

Source Tissue Comment Organism Textmining
lung
-
Homo sapiens
-
lung
-
Mus musculus
-
lung
-
Rattus norvegicus
-
lung epithelial cell
-
Homo sapiens
-
lung epithelial cell
-
Mus musculus
-
lung epithelial cell
-
Rattus norvegicus
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
LPCAT activities of wild-type and mutant recombinant Prdx6, lungs isolated from wild-type and mutant mice, and lentiviral vector-infected mouse pulmonary microvascular endothelial cells (MPMVECs), overview Mus musculus
0.0004
-
purified unphosphorylated recombinant mutant D31A enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Mus musculus
0.024
-
purified unphosphorylated recombinant enzyme, pH 7.0, 30°C, substrates LPC and palmitoyl CoA Homo sapiens
0.028
-
purified unphosphorylated recombinant enzyme, pH 7.0, 30°C, substrates LPC and palmitoyl CoA Rattus norvegicus
0.059
-
purified unphosphorylated recombinant mutant C47S enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Mus musculus
0.064
-
purified unphosphorylated recombinant mutant S32A enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Mus musculus
0.065
-
purified unphosphorylated recombinant enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Homo sapiens
0.065
-
purified unphosphorylated recombinant mutant H26A enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Mus musculus
0.065
-
purified unphosphorylated recombinant wild-type enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Mus musculus
0.066
-
purified unphosphorylated recombinant mutant D140A enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Mus musculus
0.068
-
purified unphosphorylated recombinant enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Rattus norvegicus
0.652
-
purified phosphorylated recombinant enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Homo sapiens
0.661
-
purified phosphorylated recombinant enzyme, pH 7.0, 30°C, substrates LPC and palmitoyl CoA Rattus norvegicus
0.662
-
purified phosphorylated recombinant enzyme, pH 4.0, 30°C, substrates LPC and palmitoyl CoA Rattus norvegicus
0.662
-
purified phosphorylated recombinant enzyme, pH 7.0, 30°C, substrates LPC and palmitoyl CoA Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information 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 Mus musculus ?
-
-
additional information 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 Homo sapiens ?
-
-
additional information 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 Rattus norvegicus ?
-
-
additional information the enzyme is highly specific for substrates palmitoyl-CoA and lysophosphatidylcholine. Lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, and lysophosphatidylserine are poor substrates, as well as stearoyl-CoA, acetyl-CoA, oleoyl-CA, and arachidonoyl-CoA Homo sapiens ?
-
-
additional information 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 Mus musculus C57BL/6J ?
-
-
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine
-
Homo sapiens CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine
-
Mus musculus CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine
-
Rattus norvegicus CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine quantification of palmitic acid by gas chromatography Homo sapiens CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine quantification of palmitic acid by gas chromatography Mus musculus CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine quantification of palmitic acid by gas chromatography Rattus norvegicus CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine
-
Mus musculus C57BL/6J CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?
palmitoyl-CoA + 1-palmitoyl-sn-glycero-3-phosphocholine quantification of palmitic acid by gas chromatography Mus musculus C57BL/6J CoA + 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
-
?

Synonyms

Synonyms Comment Organism
hPrdx6
-
Homo sapiens
LPCAT
-
Homo sapiens
LPCAT
-
Mus musculus
LPCAT
-
Rattus norvegicus
lysophosphatidylcholine acyl transferase
-
Homo sapiens
lysophosphatidylcholine acyl transferase
-
Mus musculus
lysophosphatidylcholine acyl transferase
-
Rattus norvegicus
mPrdx6
-
Mus musculus
rPrdx6
-
Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at Homo sapiens
30
-
assay at Mus musculus
30
-
assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
assay at Homo sapiens
7
-
assay at Mus musculus
7
-
assay at Rattus norvegicus

General Information

General Information Comment Organism
additional information amino acid D31 is crucial for LPCAT activity Homo sapiens
additional information amino acid D31 is crucial for LPCAT activity Mus musculus
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 Homo sapiens
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 Rattus norvegicus
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 Mus musculus