GO:0047190 2-acylglycerophosphocholine O-acyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0047190 describes the enzymatic activity that transfers an acyl group from acyl-CoA to 2-acyl-sn-glycero-3-phosphocholine, producing phosphatidylcholine and CoA.
• This activity is also known as 2-acylglycerophosphocholine acyltransferase and is involved in the remodeling pathway of phosphatidylcholine biosynthesis.
• The enzyme is sensitive to lipid peroxidation, which can inhibit its activity in neural membranes.
• Peroxisome proliferators selectively increase the acylation of 1-acylglycerophosphorylcholine in rodent liver, linking this activity to lipid metabolism regulation.
• Stearoyl-CoA desaturase and this acyltransferase together regulate the acyl composition of phosphatidylcholine in rat liver.
• Studying GO:0047190 helps understand membrane lipid homeostasis and its disruption in metabolic and neurological disorders [3,4].
Description
GO:0047190, 2-acylglycerophosphocholine O-acyltransferase activity, is a molecular function that catalyzes the transfer of an acyl group from acyl-CoA to 2-acyl-sn-glycero-3-phosphocholine, yielding 1,2-diacyl-sn-glycero-3-phosphocholine and CoA. This reaction is a key step in the Lands cycle, a remodeling pathway that introduces polyunsaturated fatty acids into phosphatidylcholine, the most abundant phospholipid in eukaryotic membranes. The activity is essential for maintaining membrane fluidity, lipid signaling, and cellular responses to metabolic stress. Researchers study this enzyme to understand how cells adjust their lipid composition under normal and pathological conditions, including peroxisome proliferation and oxidative stress [2,3]. Because phosphatidylcholine is critical for membrane integrity and signaling, dysregulation of this activity has been implicated in liver disease, neurodegeneration, and metabolic disorders [3,4]. The enzyme has been characterized in various tissues, including porcine erythrocyte membranes and rat central nervous system [1,3]. Its sensitivity to lipid peroxidation suggests a role in oxidative stress-related pathologies. Understanding GO:0047190 provides insights into lipid metabolic networks and potential therapeutic targets.
2-acylglycerophosphocholine O-acyltransferase activity At A Glance
| GO ID | GO:0047190 |
|---|---|
| GO term | 2-acylglycerophosphocholine O-acyltransferase activity |
| Ontology | molecular_function |
| Synonym | 2-acylglycerol-3-phosphorylcholine acyltransferase activity; 2-acylglycerophosphocholine acyltransferase activity; acyl-CoA:2-acyl-sn-glycero-3-phosphocholine O-acyltransferase activity |
| Major function | Catalyzes the acylation of 2-acyl-sn-glycero-3-phosphocholine to form phosphatidylcholine and CoA |
| Reaction | 2-acyl-sn-glycero-3-phosphocholine + acyl-CoA = 1,2-diacyl-sn-glycero-3-phosphocholine + CoA |
| Substrates | 2-acyl-sn-glycero-3-phosphocholine and acyl-CoA |
| Products | 1,2-diacyl-sn-glycero-3-phosphocholine and CoA |
| Pathway | Phosphatidylcholine remodeling (Lands cycle) |
What Is GO:0047190?
According to the Gene Ontology, GO:0047190 is defined as the catalysis of the reaction: 2-acyl-sn-glycero-3-phosphocholine + acyl-CoA = 1,2-diacyl-sn-glycero-3-phosphocholine + CoA. In simpler terms, it is an enzyme activity that adds a fatty acid chain to a lysophosphatidylcholine molecule, converting it into a full phosphatidylcholine. This activity is part of the phospholipid remodeling pathway and is also known as 2-acylglycerophosphocholine acyltransferase or acyl-CoA:2-acyl-sn-glycero-3-phosphocholine O-acyltransferase [1,2].
Why Is 2-acylglycerophosphocholine O-acyltransferase activity Important in Cell Biology?
GO:0047190 is important because it governs the final step in phosphatidylcholine remodeling, a process that determines the fatty acid composition of cell membranes and influences membrane fluidity, lipid raft formation, and signaling. Perturbations in this activity have been linked to lipid peroxidation-induced neural membrane damage and to peroxisome proliferator responses in liver [2,3]. The enzyme also interacts with stearoyl-CoA desaturase to regulate acyl composition, highlighting its role in metabolic control. Thus, understanding this activity is crucial for lipid biology, metabolic disease, and neurobiology research.
• Maintains membrane phosphatidylcholine composition and fluidity.
• Involved in the Lands cycle of phospholipid remodeling.
• Regulated by peroxisome proliferators in liver.
• Inhibited by lipid peroxidation in neural membranes.
• Interacts with stearoyl-CoA desaturase to control acyl composition.
• Relevant to metabolic disorders and neurodegeneration [3,4].
• Potential target for modulating lipid signaling.
• Characterized in erythrocyte membranes and CNS fractions [1,3].
• Contributes to hepatic lipid homeostasis [2,4].
• Provides a model for studying enzyme kinetics in lipid metabolism.
Molecular Mechanism of 2-acylglycerophosphocholine O-acyltransferase activity
Substrate Binding and Acyl Transfer
In simple terms: The enzyme grabs a lysophosphatidylcholine and a fatty acyl-CoA, then moves the fatty acid onto the lysophospholipid.
The enzyme binds 2-acyl-sn-glycero-3-phosphocholine and acyl-CoA, facilitating the transfer of the acyl group to the sn-1 position of the lysophospholipid, releasing CoA and forming phosphatidylcholine. This reaction is part of the remodeling pathway that introduces specific fatty acids into phospholipids.
Cofactors and Cofactor Requirements
In simple terms: No special cofactors are needed beyond the substrates themselves.
The reaction uses acyl-CoA as the acyl donor and does not require additional cofactors such as ATP or metal ions. The enzyme activity is measured by following the incorporation of radiolabeled acyl-CoA into phosphatidylcholine [1,2].
Regulation by Lipid Environment
In simple terms: The enzyme's activity can be turned down by oxidative damage to membranes.
Lipid peroxidation inhibits oleoyl-CoA:1-acyl-sn-glycero-3-phosphocholine O-acyltransferase in rat CNS axolemma-enriched fractions, suggesting that oxidative stress can impair this remodeling step. This sensitivity may contribute to membrane dysfunction in neurodegenerative conditions.
Role in Phosphatidylcholine Remodeling
In simple terms: This enzyme helps tailor the fatty acid composition of phosphatidylcholine after it is initially made.
The acylation of 1-acylglycerophosphorylcholine is selectively increased in livers of rats and mice treated with peroxisome proliferators, indicating that this activity is part of the adaptive response to peroxisome proliferation. Together with stearoyl-CoA desaturase, it regulates the acyl composition of phosphatidylcholine in rat liver.
Key Genes Involved in GO:0047190 2-acylglycerophosphocholine O-acyltransferase activity
The following genes and proteins are associated with or studied in the context of 2-acylglycerophosphocholine O-acyltransferase activity, based on published biochemical and physiological studies.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LPCAT1 | Lysophosphatidylcholine acyltransferase 1 | Candidate enzyme for this activity; not directly cited in provided references but commonly studied in phosphatidylcholine remodeling |
| LPCAT2 | Lysophosphatidylcholine acyltransferase 2 | Potential enzyme with similar activity; not directly cited in provided references |
| LPCAT3 | Lysophosphatidylcholine acyltransferase 3 | Involved in phospholipid remodeling; not directly cited in provided references |
| LPCAT4 | Lysophosphatidylcholine acyltransferase 4 | May contribute to acylation; not directly cited in provided references |
| SCD | Stearoyl-CoA desaturase | Regulates acyl composition together with this activity |
| ACSL | Acyl-CoA synthetase | Provides acyl-CoA substrates; not directly cited in provided references |
| PLA2 | Phospholipase A2 | Generates lysophospholipid substrates; not directly cited in provided references |
| CEPT1 | Choline/ethanolamine phosphotransferase 1 | Involved in phosphatidylcholine synthesis; not directly cited in provided references |
| PEMT | Phosphatidylethanolamine N-methyltransferase | Alternative pathway for phosphatidylcholine synthesis; not directly cited in provided references |
| PPARA | Peroxisome proliferator-activated receptor alpha | Mediates peroxisome proliferator effects on this activity |
| PPARG | Peroxisome proliferator-activated receptor gamma | Potential regulator; not directly cited in provided references |
| GPAM | Glycerol-3-phosphate acyltransferase | Related acyltransferase; not directly cited in provided references |
| AGPAT | 1-acylglycerol-3-phosphate O-acyltransferase | Similar acyltransferase activity; not directly cited in provided references |
| DGAT | Diacylglycerol O-acyltransferase | Related acyltransferase; not directly cited in provided references |
| MBOAT | Membrane-bound O-acyltransferase family | Enzyme family containing some lysophospholipid acyltransferases; not directly cited in provided references |
How Is 2-acylglycerophosphocholine O-acyltransferase activity Regulated?
The activity of 2-acylglycerophosphocholine O-acyltransferase is regulated by peroxisome proliferators, which selectively increase the acylation of 1-acylglycerophosphorylcholine in rodent liver. Additionally, stearoyl-CoA desaturase influences the acyl composition of phosphatidylcholine, indirectly affecting the substrate pool for this enzyme. Lipid peroxidation inhibits the enzyme in neural membranes, indicating redox regulation.
2-acylglycerophosphocholine O-acyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LPCAT3 | Metabolic liver disease, atherosclerosis | Liver-specific knockout mouse |
| SCD | Obesity, insulin resistance | Knockout or point-mutation cell models |
| PPARA | Peroxisome proliferation, liver cancer | Overexpression in hepatocytes |
| PLA2 | Neurodegeneration, inflammation | Knock-in of mutant forms in neurons |
| LPCAT1 | Cancer, lipid metabolism | CRISPR knockout in cancer cell lines |
Neurodegeneration and Oxidative Stress
Lipid peroxidation inhibits oleoyl-CoA:1-acyl-sn-glycero-3-phosphocholine O-acyltransferase in rat CNS axolemma-enriched fractions, suggesting that oxidative stress may impair phosphatidylcholine remodeling in neurodegenerative conditions. This inhibition could contribute to membrane damage and neuronal dysfunction.
Metabolic Liver Disease
Peroxisome proliferators increase the acylation of 1-acylglycerophosphorylcholine in livers of rats and mice, linking this activity to hepatic lipid metabolism and potential liver disease states. The interplay with stearoyl-CoA desaturase further implicates it in fatty liver and metabolic syndrome.
From 2-acylglycerophosphocholine O-acyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of enzyme activity alter phosphatidylcholine composition? | CRISPR knockout of candidate LPCAT genes in HeLa or HepG2 cells |
| Does a point mutation affect catalytic efficiency? | Knock-in of catalytic site mutations in cell lines |
| Can overexpression rescue lipid peroxidation-induced damage? | Overexpression of LPCAT in neuronal cells |
| How does peroxisome proliferator treatment affect activity? | Wild-type and PPARA knockout mouse hepatocytes |
| What is the role of stearoyl-CoA desaturase in acyl remodeling? | SCD knockout or overexpression in liver cells |
| Can tagged enzyme be used for localization studies? | Knock-in of FLAG-tagged LPCAT in cell lines |
How to Study the 2-acylglycerophosphocholine O-acyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiometric acyltransferase assay | Enzyme activity using radiolabeled acyl-CoA | Measure activity in tissue homogenates |
| LC-MS lipidomics | Phosphatidylcholine species and acyl composition | Assess changes after gene knockout |
| qRT-PCR | mRNA expression of candidate genes | Evaluate transcriptional regulation |
| Western blot | Protein levels of candidate enzymes | Validate knockout or overexpression |
| CRISPR knockout screening | Gene requirement for activity | Identify novel regulators |
| Immunofluorescence | Subcellular localization | Determine membrane distribution |
| Lipid peroxidation assays | Oxidative stress markers | Correlate with enzyme inhibition |
Enzymatic Activity Assays
Radiometric assays using radiolabeled acyl-CoA and 2-acyl-sn-glycero-3-phosphocholine are standard for measuring this activity in membrane fractions [1,2]. These assays quantify the incorporation of labeled acyl groups into phosphatidylcholine.
Lipidomics and Mass Spectrometry
Mass spectrometry-based lipidomics can profile phosphatidylcholine species and assess changes in acyl composition upon enzyme manipulation. This approach is useful for linking activity to cellular lipid profiles.
Gene Expression Analysis
Quantitative PCR and RNA-seq can measure expression of candidate genes under conditions that modulate activity, such as peroxisome proliferator treatment. This helps identify transcriptional regulation.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes that affect phosphatidylcholine remodeling and enzyme activity, using lipid-sensitive reporters or mass spectrometry readouts.
How CRISPR Can Be Used to Study GO:0047190 2-acylglycerophosphocholine O-acyltransferase activity
Knockout
CRISPR knockout of candidate LPCAT genes in cell lines can abolish 2-acylglycerophosphocholine O-acyltransferase activity, allowing researchers to measure its contribution to phosphatidylcholine remodeling and cellular lipid composition.
Point Mutation
Introducing point mutations in the catalytic domain of candidate enzymes via CRISPR can help identify essential residues for acyl transfer and distinguish this activity from other acyltransferases.
Knock-in
Knock-in of epitope tags or fluorescent proteins at the endogenous locus enables tracking of enzyme localization and interaction partners without overexpression artifacts.
Overexpression
CRISPR activation or cDNA overexpression can increase enzyme levels to study gain-of-function effects on lipid metabolism and resistance to lipid peroxidation.
How EDITGENE Supports 2-acylglycerophosphocholine O-acyltransferase activity Research
Researchers studying 2-acylglycerophosphocholine O-acyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in phosphatidylcholine remodeling, metabolic regulation, or disease. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for 2-acylglycerophosphocholine O-acyltransferase activity research.
Frequently Asked Questions About 2-acylglycerophosphocholine O-acyltransferase activity
What is 2-acylglycerophosphocholine O-acyltransferase activity?
It is a molecular function defined by GO:0047190 that catalyzes the transfer of an acyl group from acyl-CoA to 2-acyl-sn-glycero-3-phosphocholine, forming phosphatidylcholine and CoA.
What genes are involved in 2-acylglycerophosphocholine O-acyltransferase activity?
Genes such as LPCAT1-4, SCD, and PPARA are associated with this activity or its regulation, though specific enzyme identity may vary by tissue [2,4].
How is this enzyme regulated?
It is regulated by peroxisome proliferators, which increase its activity in liver, and is inhibited by lipid peroxidation in neural membranes [2,3].
What diseases are linked to this activity?
Neurodegeneration and metabolic liver disease have been linked to altered activity through oxidative stress and peroxisome proliferator responses [2,3].
What is the reaction catalyzed by GO:0047190?
2-acyl-sn-glycero-3-phosphocholine + acyl-CoA = 1,2-diacyl-sn-glycero-3-phosphocholine + CoA.
How can I measure this enzyme activity?
Radiometric assays using radiolabeled acyl-CoA and lysophosphatidylcholine are commonly used [1,2].
Is this enzyme sensitive to oxidative stress?
Yes, lipid peroxidation inhibits its activity in rat CNS axolemma-enriched fractions.
What is the role of stearoyl-CoA desaturase in this process?
Stearoyl-CoA desaturase and this acyltransferase together regulate the acyl composition of phosphatidylcholine in rat liver.
Can CRISPR be used to study this activity?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models can be used to dissect gene function related to this activity.
What model systems are used to study GO:0047190?
Cell lines, primary hepatocytes, and rodent models are commonly used, with assays in membrane fractions [1,2,3].
Conclusion
GO:0047190, 2-acylglycerophosphocholine O-acyltransferase activity, is a critical enzymatic step in phosphatidylcholine remodeling, influencing membrane composition and cellular responses to metabolic and oxidative stress. Its regulation by peroxisome proliferators and inhibition by lipid peroxidation highlight its importance in liver and neural physiology [2,3]. Studying this activity with CRISPR-based models can reveal causal roles in disease and identify therapeutic targets. EDITGENE offers comprehensive services to support such research.
References
- 1. Mizuno M et al.. 1984. Properties of acyl-coenzyme A:1-acylglycerophosphate acyltransferase and lipases in porcine erythrocyte membranes.. J Lipid Res 25(8):843-50 PMID: 6491529
- 2. Kawashima Y et al.. 1984. Selective increase in acylation of 1-acylglycerophosphorylcholine in livers of rats and mice by peroxisome proliferators.. Biochim Biophys Acta 793(2):232-7 PMID: 6712968
- 3. Alberghina M et al.. 1993. Lipid peroxidation inhibits oleoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine O-acyltransferase in rat CNS axolemma-enriched fractions.. Neurochem Int 23(3):229-37 PMID: 8220169
- 4. Kawashima Y et al.. 1985. Role of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine acyltransferase in the regulation of the acyl composition of phosphatidylcholine in rat liver.. Biochim Biophys Acta 837(3):222-9 PMID: 2865977
