Recent Progress in N-Acylethanolamine Research: Biological Functions and Metabolism Regulated by Two Distinct N-Acyltransferases: cPLA2ε and PLAAT Enzymes
Abstract
1. Introduction
2. cPLA2ε
2.1. cPLA2ε Functions as a Ca2+-Dependent N-Acyltransferase
2.2. cPLA2ε in the Brain
2.2.1. Neonatal Development
2.2.2. Ischemia
2.3. cPLA2ε in the Skin
2.4. cPLA2ε in Other Tissues
2.5. cPLA2γ and ABHD4 Potentially Contribute to the Conversion of NAPEs to NAEs
3. The PLAAT Family
3.1. The PLAAT Family Functions as Ca2+-Independent N-/O-Acyltransferases and PLA1/A2s
3.2. PLAAT5 Functions as a Ca2+-Independent N-Acyltransferase Producing Anti-Inflammatory NAEs in the Testis
3.3. Deficiency of PLAAT1 or PLAAT3 Ameliorates High-Fat Diet-Induced Obesity
3.4. Roles of PLAAT Proteins in Organellar Membrane Degradation
3.5. Other PLAATs
4. Concluding Remarks
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABHD4 | α/β-hydrolase domain-containing 4 |
AD | Alzheimer’s disease |
AdPLA2 | adipose-specific PLA2 |
AEA | N-arachidonoylethanolamine |
CdCl2 | cadmium chloride |
cPLA2 | cytosolic phospholipase A2 |
DHA | docosahexaenoic acid |
DHEA | N-docosahexaenoylethanolamine |
DPEA | N-docosapentaenoylethanolamine |
EPA | eicosapentaenoic acid |
GDE | glycerophosphodiesterase |
GP-NAE | glycerophospho-NAE |
HFD | high-fat diet |
IMQ | imiquimod |
iPLA2 | Ca2+-independent phospholipase A2 |
LRAT | lecithin-retinol acyltransferase |
lysoPA | lysophosphatidic acid |
NAE | N-acylethanolamine |
NAPE | N-acyl-phosphatidylethanolamine |
NAPE-PLD | NAPE-hydrolyzing phospholipase D |
NAPS | N-acyl-phosphatidylserine |
OEA | N-oleoylethanolamine |
PA | phosphatidic acid |
PC | phosphatidylcholine |
PE | phosphatidylethanolamine |
PEA | N-palmitoylethanolamine |
PI | phosphatidylinositol |
PIP2 | phosphatidylinositol 4,5-bisphosphate |
PLA1 | phospholipase A1 |
PLA2 | phospholipase A2 |
PLAAT | phospholipase A and acyltransferase |
PPARα | peroxisome proliferator-activated receptor α |
PS | phosphatidylserine |
SEA | N-stearoylethanolamine |
WAT | white adipose tissue |
WT | wild type |
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Name Enzyme (Gene) | Enzyme Activity | Ca2+ Dependency | ||
---|---|---|---|---|
PLA1/A2 | Lysophospholipase | Transacylase | ||
cPLA2α (PLA2G4A) | ++ (PLA2) | ± | ± | Yes |
cPLA2β (PLA2G4B) | + (PLA1 = PLA2) | ++ | ND | Yes |
cPLA2γ (PLA2G4C) | ++ (PLA2) | ++ | ++ (O-acyltransferase) | No |
cPLA2δ (PLA2G4D) | + (PLA1 > PLA2) | + | + (O-acyltransferase) | Yes |
cPLA2ε (PLA2G4E) | ± | − | ++ (N-acyltransferase) | Yes |
cPLA2ζ (PLA2G4F) | ++ (PLA2) | + | ND | Yes |
Name | Synonym | Enzyme Activity | Organelle- Degrading Activity | ||
---|---|---|---|---|---|
PLA1/A2 | N-Acyltransferase | O-Acyltransferase | |||
PLAAT1 | A-C1, HRASLS1 | + | ++ | ++ | Yes |
PLAAT2 | HRASLS2 | ++ | +++ | ++ | Yes |
PLAAT3 | AdPLA, HRASLS3, H-rev107, PLA2G16 | +++ | ± | + | Yes |
PLAAT4 | HRASLS4, RARRE3, RIG1, TIG3 | ++ | ± | + | Yes |
PLAAT5 | HRASLS5, iNAT | + | + | + | ND |
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Uyama, T.; Sasaki, S.; Okada-Iwabu, M.; Murakami, M. Recent Progress in N-Acylethanolamine Research: Biological Functions and Metabolism Regulated by Two Distinct N-Acyltransferases: cPLA2ε and PLAAT Enzymes. Int. J. Mol. Sci. 2025, 26, 3359. https://doi.org/10.3390/ijms26073359
Uyama T, Sasaki S, Okada-Iwabu M, Murakami M. Recent Progress in N-Acylethanolamine Research: Biological Functions and Metabolism Regulated by Two Distinct N-Acyltransferases: cPLA2ε and PLAAT Enzymes. International Journal of Molecular Sciences. 2025; 26(7):3359. https://doi.org/10.3390/ijms26073359
Chicago/Turabian StyleUyama, Toru, Sumire Sasaki, Miki Okada-Iwabu, and Makoto Murakami. 2025. "Recent Progress in N-Acylethanolamine Research: Biological Functions and Metabolism Regulated by Two Distinct N-Acyltransferases: cPLA2ε and PLAAT Enzymes" International Journal of Molecular Sciences 26, no. 7: 3359. https://doi.org/10.3390/ijms26073359
APA StyleUyama, T., Sasaki, S., Okada-Iwabu, M., & Murakami, M. (2025). Recent Progress in N-Acylethanolamine Research: Biological Functions and Metabolism Regulated by Two Distinct N-Acyltransferases: cPLA2ε and PLAAT Enzymes. International Journal of Molecular Sciences, 26(7), 3359. https://doi.org/10.3390/ijms26073359