GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0047184 describes the enzymatic activity that converts 1-acyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine, LPC) into phosphatidylcholine (PC) by transferring an acyl chain from acyl-CoA.
• This activity is also known as lysophosphatidylcholine acyltransferase (LPCAT) activity and is central to the Lands cycle of phospholipid remodeling.
• LPCAT enzymes (LPCAT1-4) are the main proteins that catalyze this reaction in mammals, with distinct tissue distributions and substrate preferences.
• Dysregulation of this activity is linked to cancer, nonalcoholic steatohepatitis (NASH), and metabolic disorders through effects on membrane composition and ferroptosis.
• The activity can be induced by peroxisome proliferators, suggesting a role in lipid metabolic adaptation.
• Studying GO:0047184 requires combining lipidomics, enzyme assays, and CRISPR-based genetic models to dissect its physiological and pathological roles.
Description
1-acylglycerophosphocholine O-acyltransferase activity (GO:0047184) is a molecular function that catalyzes the acylation of lysophosphatidylcholine (LPC) to form phosphatidylcholine (PC), using acyl-CoA as the acyl donor. This reaction is a key step in the Lands cycle, a major pathway for phospholipid remodeling that maintains membrane lipid composition and diversity. The activity is essential for generating mature PC species with specific acyl chains, which influence membrane fluidity, curvature, and signaling. Researchers study this activity because it impacts diverse physiological processes, from lipid homeostasis to immune responses, and its dysregulation is implicated in cancer, liver disease, and metabolic disorders. Understanding the enzymes that carry out this reaction, primarily the LPCAT family, provides insights into how cells adapt to metabolic stress and how pathological states arise.
1-acylglycerophosphocholine O-acyltransferase activity At A Glance
| GO ID | GO:0047184 |
|---|---|
| GO term | 1-acylglycerophosphocholine O-acyltransferase activity |
| Ontology | molecular_function |
| Synonym | Lysophosphatidylcholine acyltransferase activity; lysolecithin acyltransferase activity; acyl-CoA:1-acyl-sn-glycero-3-phosphocholine O-acyltransferase activity |
| Major function | Catalyzes the conversion of lysophosphatidylcholine to phosphatidylcholine using acyl-CoA |
| Reaction | 1-acyl-sn-glycero-3-phosphocholine + acyl-CoA = phosphatidylcholine + CoA |
| Pathway | Lands cycle of phospholipid remodeling |
| Enzymes | LPCAT1, LPCAT2, LPCAT3, LPCAT4 (and related acyltransferases) |
| Tissue distribution | Ubiquitous, with highest expression in liver, lung, and immune cells |
What Is GO:0047184?
In our own words, GO:0047184 refers to the enzymatic activity that transfers an acyl group from an acyl-CoA molecule to the sn-2 position of 1-acyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine), producing phosphatidylcholine and free CoA. This activity is synonymous with lysophosphatidylcholine acyltransferase (LPCAT) activity and is a critical component of the phospholipid remodeling pathway known as the Lands cycle.
Why Is 1-acylglycerophosphocholine O-acyltransferase activity Important in Cell Biology?
This activity is fundamental to maintaining the structural and functional diversity of cellular membranes, as it determines the acyl chain composition of phosphatidylcholine, the most abundant phospholipid in eukaryotic membranes. By remodeling LPC to PC, it prevents the accumulation of lysophospholipids, which can be cytotoxic and pro-inflammatory. Moreover, the activity influences membrane fluidity, lipid raft formation, and the availability of polyunsaturated fatty acids for signaling and ferroptosis. Consequently, it plays a central role in health and disease, from cancer progression to metabolic liver disease.
• Maintains membrane phospholipid homeostasis by converting lysophosphatidylcholine to phosphatidylcholine.
• Regulates the acyl chain composition of phosphatidylcholine, affecting membrane fluidity and function.
• Prevents accumulation of lysophosphatidylcholine, which is cytotoxic and pro-inflammatory.
• Modulates ferroptosis sensitivity by controlling polyunsaturated fatty acid incorporation into membranes.
• Influences cancer progression, including colorectal cancer and immunotherapy response.
• Contributes to the pathogenesis of nonalcoholic steatohepatitis (NASH) and liver injury.
• Plays a role in adipose tissue expansion and metabolic adaptation.
• Can be induced by peroxisome proliferators, linking it to lipid metabolic regulation.
• Serves as a potential therapeutic target for metabolic and inflammatory diseases.
• Provides a biochemical node for understanding lipid remodeling in physiology and disease.
What Happens During 1-acylglycerophosphocholine O-acyltransferase activity?
Substrate recognition and binding
In simple terms: The enzyme grabs a lysophosphatidylcholine molecule and an acyl-CoA molecule.
The enzyme first binds 1-acyl-sn-glycero-3-phosphocholine (LPC) and acyl-CoA. LPC is a lysophospholipid with a free hydroxyl at the sn-2 position, while acyl-CoA carries an activated fatty acid. The binding site accommodates both substrates, positioning the acyl-CoA thioester for nucleophilic attack by the LPC hydroxyl.
Acyl transfer and product formation
In simple terms: The fatty acid is transferred from acyl-CoA to LPC, making phosphatidylcholine.
The hydroxyl group of LPC attacks the thioester carbonyl of acyl-CoA, leading to the transfer of the acyl chain to the sn-2 position of LPC. This forms phosphatidylcholine and releases coenzyme A (CoA). The reaction is a classic acyltransferase mechanism, often involving a catalytic histidine or serine residue.
Membrane integration and remodeling
In simple terms: The new phosphatidylcholine becomes part of the cell membrane, changing its properties.
The newly synthesized phosphatidylcholine is incorporated into cellular membranes, where it contributes to the lipid bilayer. This remodeling alters membrane fluidity, curvature, and the formation of lipid microdomains, impacting signal transduction and protein function.
Regulation by substrate availability and enzyme expression
In simple terms: The speed of the reaction depends on how much LPC and acyl-CoA are available and how much enzyme is present.
The activity is regulated by the availability of LPC and acyl-CoA, as well as by the expression levels of LPCAT enzymes. Hormones, nutrients, and inflammatory signals can influence enzyme expression. For example, peroxisome proliferators induce the activity in rat kidney, linking it to peroxisomal beta-oxidation.
Role in ferroptosis and disease
In simple terms: When this activity is too high or too low, it can affect how cells die and contribute to diseases.
LPCAT3, a key enzyme for this activity, incorporates polyunsaturated fatty acids into phosphatidylcholine, making cells susceptible to ferroptosis, an iron-dependent form of cell death. Modulation of this activity can influence cancer cell survival and immune responses. In NASH, altered phospholipid remodeling contributes to mitochondrial dysfunction and liver injury.
Key Genes Involved in GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity
The following genes encode enzymes that exhibit 1-acylglycerophosphocholine O-acyltransferase activity or are directly involved in the Lands cycle of phospholipid remodeling.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LPCAT1 | Lysophosphatidylcholine acyltransferase 1; catalyzes LPC to PC conversion | Implicated in cancer, lung surfactant production, and ferroptosis regulation |
| LPCAT2 | Lysophosphatidylcholine acyltransferase 2; also acetyltransferase activity | Involved in inflammatory responses and colorectal cancer progression |
| LPCAT3 | Lysophosphatidylcholine acyltransferase 3; prefers polyunsaturated acyl-CoAs | Key regulator of ferroptosis, lipid metabolism, and NASH |
| LPCAT4 | Lysophosphatidylcholine acyltransferase 4; also acts on other lysophospholipids | Less studied; potential role in skin and brain lipid metabolism |
| MBOAT1 | Membrane-bound O-acyltransferase domain-containing 1; may have LPCAT activity | Associated with bone density and lipid metabolism |
| MBOAT2 | Membrane-bound O-acyltransferase domain-containing 2; LPCAT-like activity | Implicated in cancer and lipid droplet formation |
| AGPAT1 | 1-acylglycerol-3-phosphate O-acyltransferase 1; related acyltransferase | Involved in triglyceride synthesis and metabolic disorders |
| AGPAT2 | 1-acylglycerol-3-phosphate O-acyltransferase 2; related acyltransferase | Mutations cause congenital generalized lipodystrophy |
| PLA2G4A | Phospholipase A2 group IVA; generates LPC for remodeling | Provides substrate for LPCAT activity; linked to inflammation |
| PLA2G6 | Phospholipase A2 group VI; calcium-independent | Generates LPC; mutations cause neurodegeneration |
| ABHD3 | Abhydrolase domain-containing 3; lysophospholipase | Regulates LPC levels and thus LPCAT activity |
| ABHD4 | Abhydrolase domain-containing 4; lysophospholipase | Modulates LPC availability |
| LCAT | Lecithin-cholesterol acyltransferase; uses PC as acyl donor | Interacts with PC metabolism; deficiency causes eye disease |
| CEPT1 | Choline/ethanolamine phosphotransferase 1; synthesizes PC | Contributes to PC pool; affects remodeling |
| CHKA | Choline kinase alpha; phosphorylates choline for PC synthesis | Upstream of PC synthesis; cancer target |
| PCYT1A | Phosphate cytidylyltransferase 1 alpha; rate-limiting in PC synthesis | Regulates PC availability for remodeling |
| SLC7A11 | Cystine/glutamate antiporter; affects ferroptosis | Linked to LPCAT2-mediated colorectal cancer suppression |
| PRMT1 | Protein arginine methyltransferase 1; regulates signaling | Interacts with LPCAT2 pathway in cancer |
How Is 1-acylglycerophosphocholine O-acyltransferase activity Regulated?
The activity of 1-acylglycerophosphocholine O-acyltransferase is regulated at multiple levels. Substrate availability of LPC and acyl-CoA directly influences reaction rate; phospholipase A2 enzymes generate LPC, while acyl-CoA synthetases activate fatty acids. Enzyme expression is controlled by transcription factors such as SREBP, which regulates lipid synthesis genes, and peroxisome proliferator-activated receptors (PPARs), as shown by induction of the activity by peroxisome proliferators in rat kidney. Additionally, post-translational modifications and membrane environment may affect enzyme activity. In disease states, inflammatory cytokines and metabolic stress can alter LPCAT expression, contributing to pathological remodeling.
1-acylglycerophosphocholine O-acyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LPCAT3 | Ferroptosis, NASH, cancer | LPCAT3 knockout or point-mutation cell lines; lipidomics and ferroptosis assays |
| LPCAT2 | Colorectal cancer | LPCAT2 overexpression and knockout in HCT116 cells; PRMT1/SLC7A11 axis analysis |
| LPCAT1 | Lung cancer, surfactant deficiency | LPCAT1 knockout mice or A549 cells; phospholipid profiling |
| SCAP/SREBP | NASH and liver carcinogenesis | Liver-specific knockout mice; high-fat diet models |
| Adipose tissue | Obesity and insulin resistance | Adipocyte-specific LPCAT knockout; dietary intervention studies |
Cancer and ferroptosis
LPCAT3-mediated incorporation of polyunsaturated fatty acids into phosphatidylcholine is a key determinant of ferroptosis sensitivity. Mefloquine enhances anti-PD-1 immunotherapy by inducing IFN-gamma-STAT1-IRF1 signaling, which upregulates LPCAT3 and promotes ferroptosis in tumors. In colorectal cancer, LPCAT2 inhibits progression via the PRMT1/SLC7A11 axis, affecting redox balance and cell survival. Thus, this activity can be either tumor-promoting or tumor-suppressive depending on context.
Nonalcoholic steatohepatitis (NASH) and liver injury
Membrane phospholipid remodeling modulates NASH progression by regulating mitochondrial homeostasis. Inhibition of SCAP/SREBP exacerbates liver injury and carcinogenesis in murine NASH, partly through altered lipid composition. LPCAT3 activity influences the balance of saturated and polyunsaturated phosphatidylcholine species, affecting hepatocyte susceptibility to stress.
Metabolic and adipose tissue disorders
Dietary control of peripheral adipose storage capacity involves membrane lipid remodeling, including LPCAT activity, which affects adipocyte expansion and insulin sensitivity. Dysregulation of this activity may contribute to obesity-related metabolic dysfunction.
Inflammatory and peroxisomal disorders
Lysophosphatidylcholine, the substrate for this activity, is a pro-inflammatory mediator; its accumulation is associated with atherosclerosis and inflammation. Induction of the activity by peroxisome proliferators suggests a role in peroxisomal beta-oxidation and related metabolic pathways.
From 1-acylglycerophosphocholine O-acyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of LPCAT3 affect ferroptosis sensitivity? | LPCAT3 knockout cell lines (e.g., HAP1, HepG2) with ferroptosis inducers |
| What is the role of LPCAT2 in colorectal cancer? | LPCAT2 overexpression and knockout in colorectal cancer cell lines |
| How does LPCAT1 contribute to lung surfactant? | LPCAT1 knockout mice or lung epithelial cells |
| Does point mutation in the catalytic site abolish activity? | CRISPR knock-in of catalytic dead LPCAT mutants |
| Can LPCAT3 overexpression protect against NASH? | Liver-specific LPCAT3 overexpression in mice fed a NASH diet |
| What is the impact of LPCAT4 on skin barrier? | LPCAT4 knockout keratinocytes and lipidomics |
How to Study the 1-acylglycerophosphocholine O-acyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| LC-MS/MS lipidomics | Phosphatidylcholine and lysophosphatidylcholine species | Profiling lipid changes in LPCAT knockout cells |
| Radioenzymatic assay | Acyltransferase activity using labeled substrates | Confirming enzymatic function of LPCAT isoforms |
| CRISPR knockout screen | Genes affecting ferroptosis or lipid metabolism | Identifying LPCAT3 as a ferroptosis regulator |
| RNA-seq | Transcript levels of LPCAT genes and related pathways | Assessing regulation by peroxisome proliferators |
| Western blot | Protein expression of LPCAT enzymes | Validating knockout or overexpression |
| Immunofluorescence | Subcellular localization of LPCAT enzymes | Determining membrane distribution |
| Co-immunoprecipitation | Protein-protein interactions | Identifying LPCAT2-PRMT1 interaction |
| Ferroptosis assays | Cell death and lipid peroxidation | Testing LPCAT3 modulation |
Enzymatic activity assays
Direct measurement of 1-acylglycerophosphocholine O-acyltransferase activity uses radiolabeled or fluorescent LPC and acyl-CoA, followed by separation of products by thin-layer chromatography or mass spectrometry. These assays are essential to confirm that a candidate gene encodes the activity.
Lipidomics and mass spectrometry
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allows comprehensive profiling of phosphatidylcholine and lysophosphatidylcholine species, revealing changes in acyl chain composition upon genetic manipulation of LPCAT enzymes.
CRISPR-based genetic screens
Genome-wide CRISPR knockout or activation screens can identify genes that regulate LPCAT activity or ferroptosis sensitivity. For example, screens have linked LPCAT3 to ferroptosis.
Transcriptomics and proteomics
RNA-seq and proteomics can assess expression changes in LPCAT genes under different conditions, such as peroxisome proliferator treatment or inflammatory stimuli.
How CRISPR Can Be Used to Study GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity
Knockout
CRISPR knockout of LPCAT genes (e.g., LPCAT3) in cell lines such as HepG2 or HAP1 abolishes the activity, leading to accumulation of LPC and altered PC species. These models are used to study ferroptosis, lipid remodeling, and liver disease.
Point Mutation
Introducing point mutations in the catalytic residues of LPCAT enzymes (e.g., histidine or serine) via CRISPR knock-in can create catalytically dead variants. These models help distinguish enzymatic activity from non-enzymatic functions.
Knock-in
Knock-in of tagged LPCAT (e.g., FLAG or GFP) allows for localization and interaction studies. Additionally, knock-in of disease-associated mutations can model human disorders.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression of LPCAT genes increases activity, enabling studies of gain-of-function effects in cancer, lipid metabolism, and ferroptosis.
How EDITGENE Supports 1-acylglycerophosphocholine O-acyltransferase activity Research
Researchers studying 1-acylglycerophosphocholine O-acyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in lipid remodeling, ferroptosis, or metabolic disease. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell models, enabling rigorous functional validation.
Contact EDITGENE today to design your custom CRISPR model for 1-acylglycerophosphocholine O-acyltransferase activity research.
Frequently Asked Questions About 1-acylglycerophosphocholine O-acyltransferase activity
What is 1-acylglycerophosphocholine O-acyltransferase activity?
It is an enzymatic activity that converts lysophosphatidylcholine to phosphatidylcholine by adding an acyl chain from acyl-CoA, also known as LPCAT activity.
What genes are involved in 1-acylglycerophosphocholine O-acyltransferase activity?
The main genes are LPCAT1, LPCAT2, LPCAT3, and LPCAT4, which encode enzymes with this activity.
What is the GO ID for lysophosphatidylcholine acyltransferase activity?
The GO ID is GO:0047184.
How is 1-acylglycerophosphocholine O-acyltransferase activity regulated?
It is regulated by substrate availability, enzyme expression via SREBP and PPARs, and post-translational modifications.
What diseases are associated with LPCAT enzymes?
They are linked to cancer, NASH, ferroptosis, and metabolic disorders.
What is the role of LPCAT3 in ferroptosis?
LPCAT3 incorporates polyunsaturated fatty acids into phosphatidylcholine, making cells susceptible to ferroptosis.
How can I study 1-acylglycerophosphocholine O-acyltransferase activity in the lab?
You can use enzymatic assays, lipidomics, CRISPR knockouts, and overexpression models.
What are the substrates of 1-acylglycerophosphocholine O-acyltransferase?
The substrates are 1-acyl-sn-glycero-3-phosphocholine (LPC) and acyl-CoA.
What is the product of the reaction catalyzed by GO:0047184?
The products are phosphatidylcholine and coenzyme A.
Can CRISPR be used to study LPCAT genes?
Yes, CRISPR knockout, knock-in, and overexpression models are widely used to study LPCAT function.
Conclusion
1-acylglycerophosphocholine O-acyltransferase activity (GO:0047184) is a central enzymatic function in phospholipid remodeling, with profound effects on membrane biology and disease. The LPCAT family enzymes that carry out this activity are implicated in cancer, liver disease, and metabolic disorders, making them attractive research targets. By combining CRISPR-based genetic models with lipidomics and functional assays, researchers can uncover the precise roles of this activity in health and disease.
References
- 1. Wang B et al.. 2019. Phospholipid Remodeling in Physiology and Disease.. Annu Rev Physiol 81:165-188 PMID: 30379616
- 2. Law SH et al.. 2019. An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases.. Int J Mol Sci 20(5) PMID: 30845751
- 3. Tao Q et al.. 2024. Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-γ-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors.. J Immunother Cancer 12(3) PMID: 38471712
- 4. Cao N et al.. 2024. LPCAT2 inhibits colorectal cancer progression via the PRMT1/SLC7A11 axis.. Oncogene 43(22):1714-1725 PMID: 38605214
- 5. Kawamura S et al.. 2022. Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis.. J Clin Invest 132(11) PMID: 35380992
- 6. Tian Y et al.. 2024. Membrane phospholipid remodeling modulates nonalcoholic steatohepatitis progression by regulating mitochondrial homeostasis.. Hepatology 79(4):882-897 PMID: 36999536
- 7. Tol MJ et al.. 2025. Dietary control of peripheral adipose storage capacity through membrane lipid remodelling.. Nat Metab 7(7):1424-1442 PMID: 40579620
- 8. Kawashima Y et al.. 1989. Induction of microsomal 1-acylglycerophosphocholine acyltransferase by peroxisome proliferators in rat kidney; co-induction with peroxisomal beta-oxidation.. Biochim Biophys Acta 1006(2):214-8 PMID: 2597669
