Information on EC 3.1.4.54 - N-acetylphosphatidylethanolamine-hydrolysing phospholipase D

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.1.4.54
-
RECOMMENDED NAME
GeneOntology No.
N-acetylphosphatidylethanolamine-hydrolysing phospholipase D
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
N-acylphosphatidylethanolamine + H2O = N-acylethanolamine + a 1,2-diacylglycerol 3-phosphate
show the reaction diagram
-
-
-
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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].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,2-dihexadecyl-sn-glycerol-3-phospho-(N-palmitoyl)ethanolamine + H2O
N-palmitoylethanolamine + 1,2-dihexadecyl-sn-glycerol-3-phosphate
show the reaction diagram
-
-
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho(N-palmitoyl)ethanolamine + H2O
1,2-dioleoyl-sn-glycero-3-phosphate + N-palmitoyl-phosphatidylethanolamine
show the reaction diagram
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
show the reaction diagram
-
-
-
-
?
N-acylphosphatidylethanolamine + H2O
N-acylethanolamine + phosphatidate
show the reaction diagram
N-arachidonoyl-1,2-dioleoyl-phosphatidylehanolamine + H2O
N-arachidonoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
hydrolysis rate with 0.1 mM N-arachidonoyl-1,2-dioleoyl-phosphatidylehanolamine is about 50% of that with 0.1 mM N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine
-
-
?
N-arachidonoyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-arachidonoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-arachidonoyl-1,2-dioleoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-arachidonoyl-1-oleoyl-2-lysophosphatidylethanolamine + H2O
N-arachidonoylethanolamine + 1-oleoyl-2-lyso-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-arachidonoyl-phosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
show the reaction diagram
-
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
show the reaction diagram
N-arachidonoylphosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
show the reaction diagram
N-butanoyl-1-palmitoyl-2-linoleoylphosphatidylethanolamine + H2O
N-butanoylethanolamine + 1-palmitoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-decanoyl-1-palmitoyl-2-linoleoylphosphatidylethanolamine + H2O
N-decanoylethanolamine + 1-palmitoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-hexanoyl-1-palmitoyl-2-linoleoylphosphatidylethanolamine + H2O
N-hexanoylethanolamine + 1-palmitoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-lauroyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-lauroylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-myristoyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-myristoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-octanoyl-1-palmitoyl-2-linoleoylphosphatidylethanolamine + H2O
N-octanoylethanolamine + 1-palmitoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-oleoyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-oleoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-oleoyl-1,2-dioleoylphosphatidylethanolamine + H2O
N-oleoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-oleoylphosphatidylethanolamine + H2O
N-oleoylethanolamine + phosphatidate
show the reaction diagram
N-palmitoyl-1,2-dilauroylphosphatidylethanolamine + H2O
N-palmitoylethanolamine + 1,2-dilauroyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-palmitoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
N-palmitoyl-1-palmitoyl-2-linoleoylphosphatidylethanolamine + H2O
N-palmitoylethanolamine + 1-palmitoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-palmitoyl-1-palmitoyl-2-lysophosphatidylethanolamine + H2O
N-palmitoylethanolamine + 1-palmitoyl-2-lyso-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-palmitoyl-1-palmitoyl-2-oleoylphosphatidylethanolamine + H2O
N-palmitoylethanolamine + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-palmitoylphosphatidylethanolamine + H2O
N-palmitoylethanolamine + phosphatidate
show the reaction diagram
N-palmitoylphosphatidylethanolamine + H2O
N-palmitoylethanolamine + phosphatidic acid
show the reaction diagram
-
-
-
?
N-stearoyl-1,2-dioleoyl-phosphatidylethanolamine + H2O
N-stearoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-stearoyl-1,2-dioleoylphosphatidylethanolamine + H2O
N-stearoylethanolamine + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
N-stearoylphosphatidylethanolamine + H2O
N-stearoylethanolamine + phosphatidate
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
N-acylphosphatidylethanolamine + H2O
N-acylethanolamine + phosphatidate
show the reaction diagram
N-arachidonoyl-phosphatidylethanolamine + H2O
N-arachidonoylethanolamine + phosphatidic acid
show the reaction diagram
-
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
show the reaction diagram
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zinc
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member of the zinc metallohydrolase family of the beta-lactamase fold
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-dihexanoyl-glycero-N-(3-(tetradecanoylamino)propyl)phosphoramidate
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i.e. AHP-71B, 96.6% inhibition at 1 mM
2-arachidonoylglycerol
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0.05 mM, 67% loss of activity
4-chloromercuribenzoic acid
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-
Ca2+
-
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capsaicin
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0.005 mM, 20% inhibition
Cd2+
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10 mM, more than 90% inhibition
Cetyltrimethylammonium chloride
strongly inhibits the enzyme of all brain regions
EDTA
-
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methyl arachidonyl fluorophosphonate
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above 0.1 mM
N-(2,4-dinitrophenyl)-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
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1 mM, 35.6% inhibition
N-(4-hydroxy-2-methylphenyl)-arachidonoylamide
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0.005 mM, 82% inhibition
N-arachidonoylethanolamine
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0.05 mM, 37% loss of activity
N-oleoylethanolamine
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0.05 mM, 36% loss of activity
N-stearoylethanolamine
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0.005 mM, 14% loss of activity
nitrocefin
-
-
noladin ether
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0.005 mM, 70% loss of activity
p-chloromercuribenzoate
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-
p-chloromercuribenzoic acid
strongly inhibits the enzyme of all brain regions
phosphatidylhexanol
-
-
receptor agonist ACEA
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0.005 mM, 56% loss of activity
Triton X-100
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-dihexanoyl-glycero-3-(hexanoylamino)propylphosphonate
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i.e. AHP-57, a phosphonic acid, activates 1.9fold at 1 mM
1,2-dioleoylphosphatidylcholine
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0.1 mM, 1.3fold stimulation
1,2-dioleoylphosphatidylethanolamine
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0.1 mM, increases activity with N-palmitoylphosphatidylamine (0.025 mM) 3.3fold, increases activity with N-arachidonoylphosphatidylamine (0.025 mM), N-oleoylphosphatidylamine (0.025 mM) and N-stearoylphosphatidylamine (0.025 mM), 2.6-2.7fold
1,2-dipalmitoylphosphatidylcholine
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0.1 mM, 1.3fold stimulation
1,2-dipalmitoylphosphatidylethanolamine
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-
15-hydroxy-N-arachidonoylethanolamine
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0.005 mM, activation to 145% of the control
cardiolipin
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from bovine liver, activates by 68% at 1 mM
methyl-1,2-dihexanoyl-glycero-3-(hexanoylamino)propylphosphonate
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i.e. AHP-38, a methylphosphonate, activates 68% at 1 mM
methyl-1,2-dihexanoyl-glycero-3-(tetradecanoylamino)propylphosphonate
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i.e. AHP-36, a methylphosphonate, activates 2fold at 1 mM
phosphatidycholine
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activates 2.75fold at 1 mM
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phosphatidylbutanol
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activates 81% at 1 mM
phosphatidylethanolamine
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activates; activates 5.91fold at 1 mM
phosphatidylinositol
-
activates 99% at 1 mM
putrescine
-
activity is increased 6fold at 10 mM
spermidine
-
EC50: about 1 mM
spermine
Triton X-100
-
maximally active at 0.05%, higher concentrations reduce activity. Synergistic activation of the enzyme by spermine and CaCl2 or by spermine and Triton X-100 is not observed
additional information
-
activator synthesis, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028
N-arachidonoyl-1,2-dioleoylphosphatidylethanolamine
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pH 7.5, 37C
0.004
N-arachidonoyl-1-oleoyl-2-lysophosphatidylethanolamine
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pH 7.5, 37C
0.04
N-arachidonoylphosphatidylethanolamine
-
pH 7.4, 37C
0.0029
N-oleoyl-1,2-dioleoylphosphatidylethanolamine
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pH 7.5, 37C
0.002 - 0.0647
N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine
0.0033
N-palmitoyl-1-palmitoyl-2-linoleoylphosphatidylethanolamine
-
pH 7.5, 37C
0.004
N-palmitoyl-1-palmitoyl-2-lysophosphatidylethanolamine
-
pH 7.5, 37C
0.0017 - 0.045
N-palmitoylphosphatidylethanolamine
0.0034
N-stearoyl-1,2-dioleoylphosphatidylethanolamine
-
pH 7.5, 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
1,2-dihexanoyl-glycero-N-(3-(tetradecanoylamino)propyl)phosphoramidate
Homo sapiens
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pH 8.0, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000193
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pH 7.4, 37C, liver
0.00002
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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
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hydrolysis of N-palmitoylphosphatidylethanolamine, homogenates of transfected cells, pH and temperature not specified in the publication
0.0979
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substrate: N-palmitoyl-1-palmitoyl-2-linoleoyl-phosphatidylethanolamine, pH 7.5, 37C
0.406
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37C, pH and temperature not specified in the publication
2.6
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37C, pH 7.4, substrate: N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine, wild-type enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
expression of NAPE-PLD in dorsal root ganglia
Manually annotated by BRENDA team
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a substantial proportion of astrocytic and microglial profiles are immunolabeled for both diacylglycerol lipase alpha and NAPE-PLD. NAPE-PLD immunoreactivity on glial profiles at the vicinity of synapses is only occasionally observed. Results suggest that both neurons and glial cells can synthesize and release anandamide in the superficial spinal dorsal horn. Anandamide can predominantly be released from nonsynaptic dendritic and glial compartments
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
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highest specific acitivity
Manually annotated by BRENDA team
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NAPE-PLD is expressed in mouse oviduct on days one to four of pregnancy
Manually annotated by BRENDA team
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NAPE-PLD is a major player in regulating the dynamic levels of anandamide in the uterus during early pregnancy
Manually annotated by BRENDA team
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ventral palladium, approximately 60% of cannabinoid-1 receptor-labeled axonal profiles oppose or converge with axon terminals containing N-acylphosphatidylethanolamine-hydrolyzing phospholipase D immunoreactivity
Manually annotated by BRENDA team
additional information
neuronal tissue distribution of NAPE-PLD expression analysis, quantitative realtime PCR
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45596
-
45596, calculated from sequence
45723
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x * 45723, calculated from sequence
45816
-
x * 45816, calculated from sequence
46000
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x * 46000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
1% (w/v) octyl glucoside improves the stability of the purified enzyme
-
one cycle of freezing and thawing causes loss of the enzyme activity up to 50%
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phenylmethylsulfonylfluoride stabilizes at high concentrations (10 mM)
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, in the presence of 1% octyl glucoside
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in COS-7 cells
-
expression in Escherichia coli
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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
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overexpression in COS-7 cells
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stable expression of NAPE-PLD in HEK-293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
capsaicin treatment overnight downregulates NAPE-PLD expression in capsaicin-sensitive cells by 70% at 0.01 mM
Nape-pld is regulated by ovarian steroid hormones via their nuclear receptors
-
the enzyme appears to be constitutively active
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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
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D389N
-
Vmax is about 87% of wild-type activity, single nucleotide polymorphism mutant
H380R
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complete loss of activity, single nucleotide polymorphism mutant
L207F
-
complete loss of activity, single nucleotide polymorphism mutant of
S152A
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Vmax is about 84% of wild-type activity, single nucleotide polymorphism mutant
367stop
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complete loss of activity
377stop
-
complete loss of activity
387stop
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Vmax is 20% of wild-type activity, slight decrease in Km-value for N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine
C170S
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Vmax is 44% of wild-type activity
C222S
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Vmax is 88% of wild-type activity
C237S
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Vmax is 90% of wild-type activity
C255S
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Vmax is 88% of wild-type activity
C288S
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Vmax is 87% of wild-type activity
D284N
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complete loss of activity
DELTAN138
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complete loss of activity
DELTAN55
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Vmax is 28% of wild-type activity, slight decrease in Km-value for N-palmitoyl-1,2-dioleoyl-phosphatidylethanolamine
DELTAN85
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complete loss of activity
H185N
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complete loss of activity
H187N
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complete loss of activity
H189N
-
complete loss of activity
H190N
-
complete loss of activity
H253N
-
complete loss of activity
H321N
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complete loss of activity
H331N
-
specific activity is about 4% of wild-type value
H343N
-
specific activity is similar to wild-type value
H353N
-
specific activity is similar to wild-type value
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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