GO:0071618 lysophosphatidylethanolamine acyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071618 describes the enzymatic activity that transfers an acyl group from acyl-CoA to lysophosphatidylethanolamine (LPE), producing phosphatidylethanolamine (PE).
• This activity is conserved from yeast to plants and mammals, with key enzymes including LPEAT1/MBOAT1, LPEAT2, and yeast Ale1.
• LPEAT activity is critical for membrane phospholipid remodeling, affecting membrane fluidity, cell growth, and differentiation.
• In Arabidopsis, LPEAT activity regulates growth and autophagy, and its knockout or overexpression alters life span.
• In mammals, LPEAT2 incorporates docosahexaenoic acid (DHA) into phospholipids and may influence fatty acid-induced cell death.
• Dysregulation of LPEAT enzymes has been linked to cardiac differentiation, neuronal morphology, and endurance training responses.
Description
Lysophosphatidylethanolamine acyltransferase (LPEAT) activity, classified as GO:0071618, is a molecular function that catalyzes the transfer of an acyl group from acyl-CoA to lysophosphatidylethanolamine, yielding phosphatidylethanolamine and CoA. This reaction is a key step in the Lands cycle of phospholipid remodeling, which maintains membrane lipid composition and asymmetry. LPEAT activity is essential for diverse biological processes, including membrane biogenesis, cell growth, and stress responses. In plants, LPEAT activity regulates growth and autophagy, with knockout of LPEAT genes leading to altered life span. In mammals, LPEAT enzymes such as LPEAT1/MBOAT1 and LPEAT2 are involved in neuronal differentiation and DHA incorporation, respectively. Given its central role in lipid metabolism, LPEAT activity is a subject of intense research in cell biology, physiology, and disease.
lysophosphatidylethanolamine acyltransferase activity At A Glance
| GO ID | GO:0071618 |
|---|---|
| GO term | lysophosphatidylethanolamine acyltransferase activity |
| Ontology | molecular_function |
| Synonym | none |
| Major function | Catalyzes acyl transfer from acyl-CoA to lysophosphatidylethanolamine, forming phosphatidylethanolamine |
| Major enzymes | LPEAT1/MBOAT1, LPEAT2, yeast Ale1 |
| Subcellular location | Endoplasmic reticulum and other membranes |
| Pathway | Lands cycle of phospholipid remodeling |
What Is GO:0071618?
GO:0071618, lysophosphatidylethanolamine acyltransferase activity, is defined as the catalysis of the transfer of acyl groups from an acyl-CoA to lysophosphatidylethanolamine. This enzymatic activity belongs to the molecular_function ontology and is part of phospholipid acyltransferase activities that remodel membrane phospholipids.
Why Is lysophosphatidylethanolamine acyltransferase activity Important in Cell Biology?
LPEAT activity is fundamental to membrane phospholipid homeostasis, influencing membrane fluidity, curvature, and protein function. It is required for normal growth and development in plants and animals, and its dysregulation has been associated with defects in cardiac differentiation, neuronal morphology, and fatty acid-induced cell death. Understanding LPEAT activity provides insights into lipid-related diseases and potential therapeutic targets.
• Maintains membrane phospholipid composition by reacylating lysophosphatidylethanolamine.
• Regulates growth and autophagy in plants, affecting life span.
• Essential for cardiac cell differentiation and function.
• Modulates neuronal morphology and function through LPEAT1/MBOAT1.
• Incorporates DHA into phospholipids via LPEAT2, impacting cell death.
• Conserved from yeast to mammals, with yeast Ale1 as a major enzyme.
• Linked to endurance training adaptations via circular RNA MBOAT2.
• Potential target for modulating lipid metabolism in disease.
Molecular Mechanism of lysophosphatidylethanolamine acyltransferase activity
Substrate recognition and binding
In simple terms: The enzyme grabs a lysophosphatidylethanolamine molecule and an acyl-CoA molecule.
LPEAT enzymes specifically bind lysophosphatidylethanolamine (LPE) and acyl-CoA as substrates. The enzyme's active site accommodates the ethanolamine headgroup of LPE and the acyl chain of acyl-CoA, facilitating the transfer reaction.
Catalytic acyl transfer
In simple terms: The enzyme moves the acyl group from acyl-CoA onto LPE, making phosphatidylethanolamine.
The catalytic mechanism involves the nucleophilic attack of the hydroxyl group of LPE on the thioester bond of acyl-CoA, resulting in the formation of phosphatidylethanolamine and free CoA. This reaction is characteristic of acyl-CoA:lysophospholipid acyltransferases.
Cofactors and membrane environment
In simple terms: The enzyme works best in a membrane setting and does not need extra cofactors.
LPEAT activity does not require additional cofactors beyond the substrates, but it is membrane-associated and likely functions at the endoplasmic reticulum. The membrane environment may influence substrate accessibility and enzyme activity.
Regulation by gene expression and isoforms
In simple terms: Different versions of the enzyme are made in different tissues and times.
LPEAT activity is regulated by the expression of distinct isoforms, such as LPEAT1/MBOAT1 and LPEAT2, which exhibit tissue-specific patterns and developmental regulation. In Arabidopsis, LPEAT genes are differentially expressed and their knockout or overexpression affects autophagy and life span.
Key Genes Involved in GO:0071618 lysophosphatidylethanolamine acyltransferase activity
The following genes encode enzymes with lysophosphatidylethanolamine acyltransferase activity or are closely associated with this function.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MBOAT1 (LPEAT1) | Major LPEAT in mammals; regulates neuronal morphology | Knockout affects neuron differentiation |
| LPEAT2 | Brain isoform; incorporates DHA into phospholipids | Linked to fatty acid-induced cell death |
| ALE1 (yeast) | Major LPEAT in Saccharomyces cerevisiae | Model for studying LPEAT function |
| LPEAT1 (Arabidopsis) | Regulates growth and autophagy | Knockout alters life span |
| LPEAT2 (Arabidopsis) | Contributes to LPEAT activity | Overexpression affects autophagy markers |
| MBOAT2 | Related acyltransferase; associated with endurance training | Circular RNA MBOAT2 changes with training |
| LPCAT3 | Lysophospholipid acyltransferase with broader specificity | May compensate in LPEAT-deficient models |
| LPCAT4 | Lysophospholipid acyltransferase | Potential overlapping functions |
| LPGAT1 | Lysophosphatidylglycerol acyltransferase | Related family member |
| LPLAT7 | Lysophospholipid acyltransferase | Possible LPEAT activity |
| LPLAT10 | Lysophospholipid acyltransferase | Possible LPEAT activity |
| LPEAT3 (Arabidopsis) | Putative LPEAT | May contribute to total activity |
| LPEAT4 (Arabidopsis) | Putative LPEAT | May contribute to total activity |
| LPEAT5 (Arabidopsis) | Putative LPEAT | May contribute to total activity |
| LPEAT6 (Arabidopsis) | Putative LPEAT | May contribute to total activity |
| LPEAT7 (Arabidopsis) | Putative LPEAT | May contribute to total activity |
| LPEAT8 (Arabidopsis) | Putative LPEAT | May contribute to total activity |
How Is lysophosphatidylethanolamine acyltransferase activity Regulated?
LPEAT activity is regulated at multiple levels. In Arabidopsis, knockout of LPEAT genes increases autophagy markers and extends life span, while overexpression has opposite effects. In mammals, LPEAT1/MBOAT1 expression is modulated during neuronal differentiation, and LPEAT2 is responsive to fatty acid availability. Cardiac endurance training alters circular RNA MBOAT2 levels, suggesting physiological regulation.
lysophosphatidylethanolamine acyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MBOAT1 | Neuronal differentiation defects | Knockout in P19C6 cells |
| LPEAT2 | Fatty acid-induced cell death | Overexpression in cell lines |
| MBOAT2 | Cardiac endurance training response | Circular RNA knockdown in cardiomyocytes |
| LPEAT1 (Arabidopsis) | Growth and autophagy dysregulation | Knockout and overexpression lines |
| ALE1 (yeast) | Membrane lipid homeostasis | Yeast deletion mutants |
Cardiac differentiation and disease
LPEAT activity is elevated during cardiac cell differentiation, and its dysregulation may contribute to cardiac pathology. Endurance training alters MBOAT2 circular RNA, linking LPEAT-related genes to cardiac adaptation.
Neurodegeneration and neuronal function
LPEAT1/MBOAT1 regulates morphology and function of P19C6 cell-derived neurons, suggesting a role in neuronal development and potentially neurodegeneration. LPEAT2 is a brain isoform that incorporates DHA, a fatty acid critical for neuronal health.
Cancer and cell death
LPEAT2 has possible functions in fatty acid-induced cell death, which may be relevant to cancer cell survival and lipid metabolism. Altered phospholipid remodeling is a hallmark of cancer, and LPEAT enzymes could influence tumor progression.
From lysophosphatidylethanolamine acyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does LPEAT1 loss affect neuronal differentiation? | MBOAT1 knockout in P19C6 cells |
| How does LPEAT2 incorporate DHA? | LPEAT2 overexpression in mammalian cells |
| What is the role of LPEAT in plant growth? | Arabidopsis LPEAT knockout and overexpression |
| Is yeast Ale1 the major LPEAT? | ALE1 deletion in Saccharomyces cerevisiae |
| Does LPEAT activity change during cardiac differentiation? | Cardiac cell differentiation model |
| How does endurance training affect MBOAT2? | Circular RNA MBOAT2 knockdown in vivo |
How to Study the lysophosphatidylethanolamine acyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radioenzymatic assay | LPEAT activity | Enzyme kinetics |
| LC-MS lipidomics | Phospholipid species | DHA incorporation |
| qRT-PCR | mRNA levels | Gene expression profiling |
| CRISPR knockout | Gene function | Loss-of-function studies |
| Overexpression | Gain-of-function | Enzyme overproduction |
| Immunofluorescence | Subcellular localization | ER localization |
| Circular RNA analysis | MBOAT2 circRNA levels | Cardiac training response |
Enzymatic activity assays
LPEAT activity can be measured using radiolabeled or fluorescent acyl-CoA and LPE substrates, followed by separation of products by thin-layer chromatography or mass spectrometry.
Gene expression analysis
Quantitative RT-PCR and RNA-seq can assess LPEAT gene expression across tissues and conditions, as shown in Arabidopsis and mammalian studies.
Lipidomics and mass spectrometry
Mass spectrometry-based lipidomics quantifies phosphatidylethanolamine species and DHA incorporation, revealing LPEAT2 function.
CRISPR-based genetic models
Knockout, knock-in, and overexpression models generated by CRISPR-Cas9 enable functional studies of LPEAT genes in cells and organisms.
How CRISPR Can Be Used to Study GO:0071618 lysophosphatidylethanolamine acyltransferase activity
Knockout
CRISPR-Cas9 knockout of LPEAT genes, such as MBOAT1 or Arabidopsis LPEATs, has been used to study loss-of-function phenotypes, including neuronal differentiation defects and altered plant growth.
Point Mutation
Point mutations can be introduced into the catalytic domain of LPEAT enzymes to dissect substrate specificity and catalytic residues, as inferred from conserved motifs.
Knock-in
Knock-in of epitope tags or fluorescent proteins allows visualization and purification of LPEAT enzymes for localization and interaction studies.
Overexpression
Overexpression of LPEAT2 or Arabidopsis LPEATs via CRISPR activation or cDNA constructs increases enzyme levels, enabling gain-of-function studies on lipid remodeling and cell death.
How EDITGENE Supports lysophosphatidylethanolamine acyltransferase activity Research
Researchers studying lysophosphatidylethanolamine acyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in lipid remodeling, cell differentiation, or disease. EDITGENE provides comprehensive CRISPR-based services to generate precise cellular and animal models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for lysophosphatidylethanolamine acyltransferase activity research.
Frequently Asked Questions About lysophosphatidylethanolamine acyltransferase activity
What is lysophosphatidylethanolamine acyltransferase activity?
It is the enzymatic activity (GO:0071618) that transfers an acyl group from acyl-CoA to lysophosphatidylethanolamine, forming phosphatidylethanolamine.
What genes are involved in lysophosphatidylethanolamine acyltransferase activity?
Key genes include MBOAT1 (LPEAT1), LPEAT2, yeast ALE1, and Arabidopsis LPEATs.
What is the function of LPEAT1?
LPEAT1/MBOAT1 regulates neuronal morphology and function, and its knockout affects differentiation.
How is LPEAT activity measured?
It is typically measured using radioenzymatic assays with labeled acyl-CoA and LPE, followed by product separation.
What is the role of LPEAT2 in DHA incorporation?
LPEAT2 incorporates docosahexaenoic acid (DHA) into phospholipids and may influence fatty acid-induced cell death.
Is LPEAT activity conserved in yeast?
Yes, yeast Ale1 is the major LPEAT and is homologous to mammalian enzymes.
How does LPEAT affect plant growth?
In Arabidopsis, LPEAT activity regulates growth and autophagy; knockout alters life span.
What diseases are linked to LPEAT enzymes?
They are linked to cardiac differentiation, neuronal function, and fatty acid-induced cell death.
Can CRISPR be used to study LPEAT genes?
Yes, CRISPR knockout, knock-in, and overexpression models are powerful tools for LPEAT research.
What is the subcellular localization of LPEAT enzymes?
They localize mainly to the endoplasmic reticulum and other membranes.
Conclusion
Lysophosphatidylethanolamine acyltransferase activity (GO:0071618) is a conserved enzymatic function essential for membrane phospholipid remodeling and diverse physiological processes. Its study has revealed critical roles in plant growth, neuronal differentiation, cardiac function, and lipid-related cell death. Continued research using CRISPR models and advanced lipidomics will further illuminate its mechanistic and therapeutic potential.
References
- 1. Jasieniecka-Gazarkiewicz K et al.. 2017. Acyl-CoA:Lysophosphatidylethanolamine Acyltransferase Activity Regulates Growth of Arabidopsis.. Plant Physiol 174(2):986-998 PMID: 28408542
- 2. Fotheringham J et al.. 2000. Lysophosphatidylethanolamine acyltransferase activity is elevated during cardiac cell differentiation.. Biochim Biophys Acta 1485(1):1-10 PMID: 10802244
- 3. Tabe S et al.. 2016. Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons.. FASEB J 30(7):2591-601 PMID: 27048541
- 4. Eto M et al.. 2020. Lysophosphatidylethanolamine acyltransferase 2 (LPEAT2) incorporates DHA into phospholipids and has possible functions for fatty acid-induced cell death.. Biochem Biophys Res Commun 526(1):246-252 PMID: 32204912
- 5. Riekhof WR et al.. 2007. Identification and characterization of the major lysophosphatidylethanolamine acyltransferase in Saccharomyces cerevisiae.. J Biol Chem 282(39):28344-28352 PMID: 17652094
- 6. Cao J et al.. 2008. Molecular identification of a novel mammalian brain isoform of acyl-CoA:lysophospholipid acyltransferase with prominent ethanolamine lysophospholipid acylating activity, LPEAT2.. J Biol Chem 283(27):19049-57 PMID: 18458083
- 7. Jasieniecka-Gazarkiewicz K et al.. 2021. Subcellular Localization of Acyl-CoA: Lysophosphatidylethanolamine Acyltransferases (LPEATs) and the Effects of Knocking-Out and Overexpression of Their Genes on Autophagy Markers Level and Life Span of A. thaliana.. Int J Mol Sci 22(6) PMID: 33809440
- 8. Meinecke A et al.. 2020. Cardiac endurance training alters plasma profiles of circular RNA MBOAT2.. Am J Physiol Heart Circ Physiol 319(1):H13-H21 PMID: 32412780
