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Information on EC 3.1.4.54 - N-acetylphosphatidylethanolamine-hydrolysing phospholipase D and Organism(s) Mus musculus and UniProt Accession Q8BH82
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3.1.4.54 N-acetylphosphatidylethanolamine-hydrolysing phospholipase DIUBMB Comments
This enzyme is involved in the biosynthesis of anandamide. It does not hydrolyse phosphatidylcholine and phosphatidylethanolamine . No transphosphatidation . The enzyme contains Zn2+ and is activated by Mg2+ or Ca2+ .
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
napepld, n-acyl phosphatidylethanolamine phospholipase d, n-acyl-phosphatidylethanolamine-specific phospholipase d, n-acylphosphatidylethanolamine-specific phospholipase d, nape-hydrolysing phospholipase d, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
NAPE-PLD
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
N-acetylphosphatidylethanolamine phosphatidohydrolase
This enzyme is involved in the biosynthesis of anandamide. It does not hydrolyse phosphatidylcholine and phosphatidylethanolamine [1]. No transphosphatidation [1]. The enzyme contains Zn2+ and is activated by Mg2+ or Ca2+ [2].
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N-arachidonoyl-phosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
the enzyme is involved in the biosynthesis of anandamide, an endocannabinoid that belongs to the class of bioactive, long-chain N-acylethanolamines. Analysis of NAPE-PLD-deficient mice reveals the presence of NAPE-PLD independent pathways for the anandamide formation
N-arachidonoylethanolamine i.e. anandamide
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidate
Km values and Vmax values for N-palmitoylphosphatidylethanolamine, N-arachidonoylphosphatidylethanolamine, N-oleoylphosphatidylethanolamine, and N-stearoylphosphatidylethanolamine are similar. The enzyme does not have selectivity for N-acyl groups of N-acylphosphatidylamines
-
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
N-oleoylphosphatidylethanolamine + H2O
N-oleoylethanolamine + phosphatidate
Km values and Vmax values for N-palmitoylphosphatidylethanolamine, N-arachidonoylphosphatidylethanolamine, N-oleoylphosphatidylethanolamine, and N-stearoylphosphatidylethanolamine are similar. The enzyme does not have selectivity for N-acyl groups of N-acylphosphatidylamines
-
-
?
N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-palmitoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
-
-
-
?
N-palmitoylphosphatidylethanolamine + H2O
N-palmitoylethanolamine + phosphatidate
Km values and Vmax values for N-palmitoyl-phosphatidylethanolamine, N-arachidonoyl-phosphatidylethanolamine, N-oleoyl-phosphatidylethanolamine, and N-stearoyl-phosphatidylethanolamine are similar. The enzyme does not have selectivity for N-acyl groups of N-acylphosphatidylamines
-
-
?
N-stearoylphosphatidylethanolamine + H2O
N-stearoylethanolamine + phosphatidate
Km values and Vmax values for N-palmitoylphosphatidylethanolamine, N-arachidonoylphosphatidylethanolamine, N-oleoylphosphatidylethanolamine, and N-stearoylphosphatidylethanolamine are similar. The enzyme does not have selectivity for N-acyl groups of N-acylphosphatidylamines
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho(N-palmitoyl)ethanolamine + H2O
1,2-dioleoyl-sn-glycero-3-phosphate + N-palmitoyl-phosphatidylethanolamine
-
-
-
-
?
1-O-octadecenyl-2-oleoyl-sn-glycero-3-phospho(N-palmitoyl)ethanolamine + H2O
1-O-octadecenyl-2-oleoyl-sn-glycerol-3-phosphate + N-palmitoyl-phosphatidylethanolamine
-
-
-
-
?
N-acylphosphatidylethanolamine + H2O
N-acylethanolamine + phosphatidate
biosynthetic enzyme of anandamide and its related bioactive congeners, the N-acylethanolamines
-
-
?
N-acylphosphatidylethanolamine + H2O
N-acylethanolamine + phosphatidate
the enzyme is involved in formation of N-acylethanolamines, membrane-derived lipids that are utilized as signaling molecules in the nervous system (e.g., the endocannabinoid anandamide)
-
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
-
-
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
-
N-arachidonoylethanolamine i.e. anandamide
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
the enzyme is involved in the biosynthesis of anandamide (N-arachidonoylethanolamine). NAPE-PLD is responsible for the conversion of N-acylphosphatidylethanolamines to N-acylethanolamines in vivo, but other enzyme(s) or pathway(s) are also involved in it, especially in the formation of polyunsaturated N-acylethanolamines, including anandamide. Unlike classical neurotransmitters and neuropeptides, endocannabinoids are not stored in vesicles in the cell, rather they are produced on demand from membrane phospholipids by a series of intracellular enzymes and released from cells, followed by immediate action as signaling molecules. Binding of endocannabinoids as well as cannabinoids to cannabinoid receptors results in the decrease in intracellular cyclic AMP level and the activation of mitogen-activated protein kinase through the coupled Gi/o proteins. The activation of cannabinoid receptors modulates ion channels through Gi/o proteins, leading to the activation of A-type and inwardly rectifying potassium channels and the inhibition of N-type and P/Q-type calcium channels. The endocannabinoid system is involved in a broad range of physiological functions, such as emotion, cardiovascular regulation, energy metabolism, and reproduction, and in a growing number of pathophysiological conditions
N-arachidonoylethanolamine i.e. anandamide
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
the enzyme is involved in the biosynthesis of anandamide, an endocannabinoid that belongs to the class of bioactive, long-chain N-acylethanolamines
N-arachidonoylethanolamine i.e. anandamide
-
?
additional information
?
-
the enzyme hydrolyzes N-acyl-2-lysophosphatidylamines at a much lower rate than N-acyl-phosphatidylethanolamines
-
-
?
additional information
?
-
-
recombinant NAPE-PLD catalyzes direct release of N-palmitoylethanolamine from N-palmitoylethanolamine plasmalogen, the reaction is also catalyzes in the brain in absence of NAPE-PLD, overview
-
-
?
additional information
?
-
-
substrate specificity of the brain enzyme, detailed overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N-arachidonoyl-phosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
the enzyme is involved in the biosynthesis of anandamide, an endocannabinoid that belongs to the class of bioactive, long-chain N-acylethanolamines. Analysis of NAPE-PLD-deficient mice reveals the presence of NAPE-PLD independent pathways for the anandamide formation
N-arachidonoylethanolamine i.e. anandamide
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
additional information
?
-
-
recombinant NAPE-PLD catalyzes direct release of N-palmitoylethanolamine from N-palmitoylethanolamine plasmalogen, the reaction is also catalyzes in the brain in absence of NAPE-PLD, overview
-
-
?
N-acylphosphatidylethanolamine + H2O
N-acylethanolamine + phosphatidate
biosynthetic enzyme of anandamide and its related bioactive congeners, the N-acylethanolamines
-
-
?
N-acylphosphatidylethanolamine + H2O
N-acylethanolamine + phosphatidate
the enzyme is involved in formation of N-acylethanolamines, membrane-derived lipids that are utilized as signaling molecules in the nervous system (e.g., the endocannabinoid anandamide)
-
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
the enzyme is involved in the biosynthesis of anandamide (N-arachidonoylethanolamine). NAPE-PLD is responsible for the conversion of N-acylphosphatidylethanolamines to N-acylethanolamines in vivo, but other enzyme(s) or pathway(s) are also involved in it, especially in the formation of polyunsaturated N-acylethanolamines, including anandamide. Unlike classical neurotransmitters and neuropeptides, endocannabinoids are not stored in vesicles in the cell, rather they are produced on demand from membrane phospholipids by a series of intracellular enzymes and released from cells, followed by immediate action as signaling molecules. Binding of endocannabinoids as well as cannabinoids to cannabinoid receptors results in the decrease in intracellular cyclic AMP level and the activation of mitogen-activated protein kinase through the coupled Gi/o proteins. The activation of cannabinoid receptors modulates ion channels through Gi/o proteins, leading to the activation of A-type and inwardly rectifying potassium channels and the inhibition of N-type and P/Q-type calcium channels. The endocannabinoid system is involved in a broad range of physiological functions, such as emotion, cardiovascular regulation, energy metabolism, and reproduction, and in a growing number of pathophysiological conditions
N-arachidonoylethanolamine i.e. anandamide
-
?
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
the enzyme is involved in the biosynthesis of anandamide, an endocannabinoid that belongs to the class of bioactive, long-chain N-acylethanolamines
N-arachidonoylethanolamine i.e. anandamide
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
dependent on, NAPE-PLD belongs to the zinc metallohydrolase family of the beta-lactamase fold
Mg2+
-
activates, methyl arachidonyl fluorophosphonate inhibits activation by Mg2+ slightly
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
15-hydroxy-N-arachidonoylethanolamine
0.005 mM, activation to 145% of the control
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00002
the endogenous NAPE-PLD activity with the homogenates of COS-7 cells transfected with the insert-free vector, pH and temperature not specified in the publication
0.019
hydrolysis of N-palmitoylphosphatidylethanolamine, homogenates of transfected cells, pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
NAPE-PLD is expressed in mouse oviduct on days one to four of pregnancy
NAPE-PLD is a major player in regulating the dynamic levels of anandamide in the uterus during early pregnancy
-
ventromedial nucleus. N-arachidonoylphosphatidylethanolamine phospholipase D is localized presynaptically and postsynaptically but shows a preferential distribution in dendrites. The dorsomedial region of the ventromedial nucleus of the hypothalamus displays the necessary machinery for the endocannabinoid-mediated modulation of synaptic transmission of brain circuitries that regulate important hypothalamic functions such as feeding behaviors
-
approximately 60% of cannabinoid-1 receptor-labeled axonal profiles oppose or converge with axon terminals containing N-acylphosphatidylethanolamine-hydrolyzing phospholipase D immunoreactivity
-
ventral palladium, approximately 60% of cannabinoid-1 receptor-labeled axonal profiles oppose or converge with axon terminals containing N-acylphosphatidylethanolamine-hydrolyzing phospholipase D immunoreactivity
additional information
a large degree of colocalization between transient receptor potential vanilloid type 1 and NAPE-PLD or fatty acid amide hydrolase, cycloxygenase-2, 12-lipoxygenase and catechol-O-methyltransferase is found in the hippocampal pyramidal neurons of the CA3 area of the Ammons horn and (with the exception of 12-lipoxyghenase) in some Purkinje cells
activity detected in almost all of the mouse organs, with higher specific activities in brain, kidney, and testis
NAPE-PLD is expressed by specific populations of neurons in the brain and targeted to axonal processes. In the dentate gyrus a strong mRNA signal is detected in granule cells. Immunocytochemical analysis reveales intense NAPE-PLD immunoreactivity in the axons of granule cells (mossy fibers) and in axons of the vomeronasal nerve that project to the accessory olfactory bulb. NAPE-PLD expression is detected in hippocampus, cortex, thalamus, hypothalamus, but the intensity of immunostaining is weaker than in mossy fibers
the enzyme concentrated presynaptically in several types of hippocampal excitatory axon terminals. Localized predominantly on the intracellular membrane cisternae of axonal calcium stores. The highest density of NAPE-PLD is found in mossy terminals of granule cells, which do not express CB1 receptors
widely distributed with higher specific activities in brain, kidney and testis
activity detected in almost all of the mouse organs, with higher specific activities in brain, kidney, and testis
widely distributed with higher specific activities in brain, kidney and testis
activity detected in almost all of the mouse organs, with higher specific activities in brain, kidney, and testis
widely distributed with higher specific activities in brain, kidney and testis
additional information
neuronal tissue distribution of NAPE-PLD expression analysis, quantitative realtime PCR
additional information
-
neuronal tissue distribution of NAPE-PLD expression analysis, quantitative realtime PCR
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
metabolism
-
NAPE-PLD-dependent and -independent, via lysophospholipase D, N-acylphosphatidylethanolamines metabolism in the brain, overview. Brain tissue N-acylethanolamines, including anandamide, can be formed from N-acylated plasmalogen through an NAPE-PLD-independent pathway as well as by their direct release via NAPE-PLD.
physiological function
additional information
-
brain homogenate also form N-palmitoylethanolamine, N-oleoylethanolamine, and anandamide from their corresponding lyso pNAPEs by a Mg2+-dependent lysophospholipase D
malfunction
generation and characterization of mice with a targeted disruption in the NAPE-PLD gene [NAPE-PLD(-/-) mice]. Brain tissue from NAPE-PLD-(-/-) mice shows more than a 5fold reduction in the calcium-dependent conversion of N-acyl-phosphatidylethanolamines to N-acylethanolamines bearing both saturated and polyunsaturated N-acyl chains. Only the former group of N-acylethanolamines is decreased in level in NAPE-PLD(-/-) brains, and these reductions are most dramatic for N-acylethanolamines bearing very long acyl chains (above C20). Further studies identified a calcium independent phospholipase D activity in brains from NAPE-PLD(-/-) mice that accepts multiple N-acylethanolamine substrates, including the anandamide precursor C20:4 N-acylphosphatidylethanolamine
malfunction
NAPE-PLD -/- mice have greatly reduced brain levels of long-chain saturated N-acylethanolamines but wild-type levels of polyunsaturated N-acylethanolamines (e.g., anandamide), suggesting an important role for NAPE-PLD in the biosynthesis of at least a subset of endogenous NAEs in the mammalian nervous system
malfunction
the enzyme is involved in the biosynthesis of anandamide, an endocannabinoid that belongs to the class of bioactive, long-chain N-acylethanolamines. Analysis of NAPE-PLD-deficient mice reveals the presence of NAPE-PLD independent pathways for the anandamide formation
physiological function
NAPE-PLD produces various long and medium chain bioactive N-acylethanolamines, including anandamide in a Ca2+-dependent fashion. Primary sensory neurons, including the capsaicin-sensitive cells are capable of producing anandamide
physiological function
the down-regulation of NAPE-PLD expression may be functionally important because mutant NAPE-PLD-null mice, in which this regulatory process is defective, are unable to mount a normal inflammatory reaction in response to carrageenan
physiological function
the enzyme is involved in formation of N-acylethanolamines, membrane-derived lipids that are utilized as signaling molecules in the nervous system (e.g., the endocannabinoid anandamide). N-acylethanolamines generated by NAPE-PLD in axons may act as anterograde synaptic signaling molecules that regulate the activity of postsynaptic neurons
physiological function
the enzyme is involved in the biosynthesis of anandamide, an endocannabinoid that belongs to the class of bioactive, long-chain N-acylethanolamines. Analysis of NAPE-PLD-deficient mice reveals the presence of NAPE-PLD independent pathways for the anandamide formation
physiological function
deletion of NAPE-PLD does not alter the N-acylethanolamine levels of heart, kidney, liver, and jejunum. N-acyl-phosphatidylethanolamine levels except in jejunum are significantly higher in NAPE-PLD-/- mice than in wild-type mice. Glycero-3-phospho-N-acylethanolamine species having an acyl moiety with 22 carbons and 6 double bonds are enriched in these peripheral tissues. 18:2-acyl-containing N-acyl-phosphatidylethanolamine species are predominant over 18:1-containing species in heart, liver, and jejunum
physiological function
feeding of post-weaning male wild-type, NAPE-PLD-/+ and NAPE-PLD -/- mice isocaloric fat diets leads to increased levels in brain docosahexaenoic acid in NAPE-PLD-/+ and NAPE-PLD-/- mice compared to wild-type consuming fish oil. In NAPE-PLD-/- mice, brain docosahexaenoylethanolamide levels are higher after fish oil feeding. Liver and jejunum arachidonoylethanolamide, 1,2-arachidonoylglycerol and docosahexaenoylethanolamide levels reflect their corresponding fatty acid precursors. NAPE-PLD -/- mice have lower oleoylethanolamide levels in the jejunum and a leaner phenotype compared to wild-type mice
physiological function
in brain of NAPE-PLD knockout mice, levels of all 6 N-acyl ethanolamines measured are significantly reduced. 2-Arachidonyl glycerol levels are significantly increased in the brainstem of knockout mice, and levels of arachidonic acid are significantly decreased exclusively in brainstem. N-arachidonoyl glycine levels are significantly increased in 4 brain regions and levels of prostaglandin PGE2 are increased in 6 of 8 brain regions in knockout mice
malfunction
-
anorectic effect of NAPE in NAPE-hydrolysing phospholipase D knockout animals, food intake studies in NAPE-PLD-/- mice, overview
malfunction
-
remarkable accumulation of 1-alkenyl-2-hydroxy-glycero-3-phospho(N-acyl)ethanolamines in the brain of NAPE-PLD-deficient mice
physiological function
-
NAPE-PLD is involved in formation of N-acylethanolamines, e.g. include anandamide, N-palmitoylethanolamine,, and N-oleoylethanolamine, from N-acylphosphatidylethanolamines in the brain
physiological function
-
approximately 60% of cannabinoid-1 receptor-labeled axonal profiles oppose or converge with axon terminals containing N-acylphosphatidylethanolamine-hydrolyzing phospholipase D immunoreactivity. Cannabinoid-1 receptors in the mouse ventral pallidum have subcellular distributions consistent with on demand activation by endocannabinoids that can regulate the release of functionally opposed opioid peptides and also modulate inhibitory and excitatory transmission
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NAPEP_MOUSE
396
0
45816
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the enzyme is not a subject to posttranslational modification
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
construction of and food intake studies in NAPE-PLD-/- mice, phenotype, overview
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
HEK-293 and CHO-K1 cell are stably transfected with mouse NAPE-PLD cDNA. Overexpressed NAPE-PLD is capable of forming N-acylethanolamines, including anandamide, in living cells. Overexpression of NAPE-PLD causes a decrease in the total amount of N-acylphosphatidylethanolamines and an increase in the total amount of N-acylethanolamines without showing obvious selectivity for N-acyl species of the endogenous N-acylphosphatidylethanolamines and N-acylethanolamines
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
capsaicin treatment overnight downregulates NAPE-PLD expression in capsaicin-sensitive cells by 70% at 0.01 mM
ethanol downregulates microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2
Nape-pld is regulated by ovarian steroid hormones via their nuclear receptors
the pro-inflammatory bacterial endotoxin, lipopolysaccharide, decreases palmitoylethanolamide biosynthesis in RAW264.7 macrophages by suppressing the transcription of NAPE-PLD, which catalyzes the production of palmitoylethanolamide and other lipid amides. Liopolysaccharide treatment reduces acetylation of histone proteins bound to the NAPE-PLD promoter, an effect that is blocked by the histone deacetylase inhibitor richostatin A. The transcription factor Sp1 is involved in regulating baseline NAPE-PLD expression, but not in the transcriptional suppression induced by lipopolysaccharide. The down-regulation of NAPE-PLD expression may be functionally important because mutant NAPE-PLD-null mice, in which this regulatory process is defective, are unable to mount a normal inflammatory reaction in response to carrageenan
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
effects of acute ethanol exposure to murine BV2 microglial cells. Ethanol downregulates microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2. Ethanol induces an increase in histone acetyltransferase activity which leads to higher levels of acetylation of histone H3
nutrition
medicine
-
the dorsomedial region of the ventromedial nucleus of the hypothalamusdisplays the necessary machinery for the endocannabinoid-mediated modulation of synaptic transmission of brain circuitries that regulate important hypothalamic functions such as feeding behaviors
nutrition
delivering of N-acylphosphatidylethanolamines and N-acylethanolamides intestinally using gut bacteria synthesizing them. Unlike in wild-type mice, increasing intestinal levels of N-acylphosphatidylethanolamines using N-acylphosphatidylethanolamine-synthesizing bacteria in Nape-Pld-/- mice fails to reduce food intake and weight gain or alter gene expression. Increasing intestinal N-acylethanolamide levels in Nape-Pld-/- mice using N-acylethanolamide-synthesizing bacteria induces all of these effects. The N-acylethanolamide-synthesizing bacteria also markedly increase N-acylethanolamide levels and decrease inflammatory gene expression in omental adipose tissue
nutrition
feeding of post-weaning male wild-type, NAPE-PLD-/+ and NAPE-PLD -/- mice isocaloric fat diets leads to increased levels in brain docosahexaenoic acid in NAPE-PLD-/+ and NAPE-PLD-/- mice compared to wild-type consuming fish oil. In NAPE-PLD-/- mice, brain docosahexaenoylethanolamide levels are higher after fish oil feeding. Liver and jejunum arachidonoylethanolamide, 1,2-arachidonoylglycerol and docosahexaenoylethanolamide levels reflect their corresponding fatty acid precursors. NAPE-PLD -/- mice have lower oleoylethanolamide levels in the jejunum and a leaner phenotype compared to wild-type mice
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ueda, N.; Okamoto, Y.; Morishita, J.
N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: a novel enzyme of the beta-lactamase fold family releasing anandamide and other N-acylethanolamines
Life Sci.
77
1750-1758
2005
Mus musculus (Q8BH82), Rattus norvegicus (Q769K2)
Egertova, M.; Simon, G.M.; Cravatt, B.F.; Elphick, M.R.
Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: A new perspective on N-acylethanolamines as neural signaling molecules
J. Comp. Neurol.
506
604-615
2008
Mus musculus (Q8BH82), Mus musculus
Fezza, F.; Gasperi, V.; Mazzei, C.; Maccarrone, M.
Radiochromatographic assay of N-acyl-phosphatidylethanolamine-specific phospholipase D activity
Anal. Biochem.
339
113-120
2005
Mus musculus (Q8BH82), Mus musculus
Okamoto, Y.; Morishita, J.; Wang, J.; Schmid, P.C.; Krebsbach, R.J.; Schmid, H.H., Ueda, N.
Mammalian cells stably overexpressing N-acylphosphatidylethanolamine-hydrolysing phospholipase D exhibit significantly decreased levels of N-acylphosphatidylethanolamines
Biochem. J.
389
241-247
2005
Mus musculus (Q8BH82)
Leung, D.; Saghatelian, A.; Simon, G.M.; Cravatt, B.F.
Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids
Biochemistry
45
4720-4726
2006
Mus musculus (Q8BH82)
Okamoto, Y.; Wang, J.; Morishita, J.; Ueda, N.
Biosynthetic pathways of the endocannabinoid anandamide
Chem. Biodivers.
4
1842-1857
2007
Homo sapiens (Q6IQ20), Mus musculus (Q8BH82), Rattus norvegicus (Q769K2)
Guo, Y.; Wang, H.; Okamoto, Y.; Ueda, N.; Kingsley, P.J.; Marnett, L.J.; Schmid, H.H.; Das, S.K.; Dey, S.K.
N-Acylphosphatidylethanolamine-hydrolyzing phospholipase D is an important determinant of uterine anandamide levels during implantation
J. Biol. Chem.
280
23429-23432
2005
Mus musculus (Q8BH82)
Nyilas, R.; Dudok, B.; Urbn, G.M.; Mackie, K.; Watanabe, M.; Cravatt, B.F.; Freund, T.F.; Katona, I.
Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals
J. Neurosci.
28
1058-1063
2008
Mus musculus (Q8BH82)
Zhu, C.; Solorzano, C.; Sahar, S.; Realini, N.; Fung, E.; Sassone-Corsi, P.; Piomelli, D.
Proinflammatory stimuli control NAPE-PLD expression in macrophages
Mol. Pharmacol.
79
786-792
2011
Mus musculus (Q8BH82)
Cristino, L.; Starowicz, K.; de Petrocellis, L.; Morishita, J.; Ueda, N.; Guglielmotti, V.; di Marzo, V.
Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain
Neuroscience
151
955-968
2008
Mus musculus (Q8BH82), Mus musculus
Nagy, B.; Fedonidis, C.; Photiou, A.; Wahba, J.; Paule, C.C.; Ma, D.; Buluwela, L.; Nagy, I.
Capsaicin-sensitive primary sensory neurons in the mouse express N-acyl phosphatidylethanolamine phospholipase D
Neuroscience
161
572-577
2009
Mus musculus (Q8BH82), Mus musculus
Wang, J.; Ueda, N.
Biology of endocannabinoid synthesis system
Prostaglandins Other Lipid Mediat.
89
112-119
2009
Canis lupus familiaris, Homo sapiens (Q6IQ20), Mus musculus (Q8BH82), Rattus norvegicus (Q769K2)
Wellner, N.; Tsuboi, K.; Madsen, A.N.; Holst, B.; Diep, T.A.; Nakao, M.; Tokumura, A.; Burns, M.P.; Deutsch, D.G.; Ueda, N.; Hansen, H.S.
Studies on the anorectic effect of N-acylphosphatidylethanolamine and phosphatidylethanolamine in mice
Biochim. Biophys. Acta
1811
508-512
2011
Mus musculus, Mus musculus C57BL/6
Tsuboi, K.; Okamoto, Y.; Ikematsu, N.; Inoue, M.; Shimizu, Y.; Uyama, T.; Wang, J.; Deutsch, D.G.; Burns, M.P.; Ulloa, N.M.; Tokumura, A.; Ueda, N.
Enzymatic formation of N-acylethanolamines from N-acylethanolamine plasmalogen through N-acylphosphatidylethanolamine-hydrolyzing phospholipase D-dependent and -independent pathways
Biochim. Biophys. Acta
1811
565-577
2011
Mus musculus, Mus musculus C57BL/6
Reguero, L.; Puente, N.; Elezgarai, I.; Ramos-Uriarte, A.; Gerrikagoitia, I.; Bueno-Lopez, J.L.; Donate, F.; Grandes, P.
Subcellular localization of NAPE-PLD and DAGL-alpha in the ventromedial nucleus of the hypothalamus by a preembedding immunogold method
Histochem. Cell Biol.
141
543-550
2014
Mus musculus
Pickel, V.M.; Shobin, E.T.; Lane, D.A.; Mackie, K.
Cannabinoid-1 receptors in the mouse ventral pallidum are targeted to axonal profiles expressing functionally opposed opioid peptides and contacting N-acylphosphatidylethanolamine-hydrolyzing phospholipase D terminals
Neuroscience
227
10-21
2012
Mus musculus
Leishman, E.; Mackie, K.; Luquet, S.; Bradshaw, H.B.
Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain
Biochim. Biophys. Acta
1861
491-500
2016
Mus musculus (Q8BH82)
Correa, F.; De Laurentiis, A.; Franchi, A.M.
Ethanol downregulates N-acyl phosphatidylethanolamine-phospholipase D expression in BV2 microglial cells via epigenetic mechanisms
Eur. J. Pharmacol.
786
224-233
2016
Mus musculus (Q8BH82)
Inoue, M.; Tsuboi, K.; Okamoto, Y.; Hidaka, M.; Uyama, T.; Tsutsumi, T.; Tanaka, T.; Ueda, N.; Tokumura, A.
Peripheral tissue levels and molecular species compositions of N-acyl-phosphatidylethanolamine and its metabolites in mice lacking N-acyl-phosphatidylethanolamine-specific phospholipase D
J. Biochem.
162
449-458
2017
Mus musculus (Q8BH82)
Chen, Z.; Zhang, Y.; Guo, L.; Dosoky, N.; de Ferra, L.; Peters, S.; Niswender, K.D.; Davies, S.S.
Leptogenic effects of NAPE require activity of NAPE-hydrolyzing phospholipase D
J. Lipid Res.
58
1624-1635
2017
Mus musculus (Q8BH82)
Lin, L.; Metherel, A.H.; Kitson, A.P.; Alashmali, S.M.; Hopperton, K.E.; Trepanier, M.O.; Jones, P.J.; Bazinet, R.P.
Dietary fatty acids augment tissue levels of n-acylethanolamines in n-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) knockout mice
J. Nutr. Biochem.
62
134-142
2018
Mus musculus (Q8BH82)
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