Information on EC 3.1.1.3 - triacylglycerol lipase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.1.1.3
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RECOMMENDED NAME
GeneOntology No.
triacylglycerol lipase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
triacylglycerol + H2O = diacylglycerol + a carboxylate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of carboxylic ester
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
retinol biosynthesis
-
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triacylglycerol degradation
-
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lipid metabolism
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Glycerolipid metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
triacylglycerol acylhydrolase
The pancreatic enzyme acts only on an ester-water interface; the outer ester links are preferentially hydrolysed.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-62-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
in ATGL or CGI-58 cause neutral lipid storage disease with myopathy and ichthyosis, respectively, in humans
metabolism
physiological function
additional information
-
HDL particles in plasma are central to regulation of hepatic lipase displacement and the hydrolytic activity of hepatic lipase, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,3-dibutyrylthio-1-propyl oleate + H2O
2,3-dibutyrylthiopropyl alcohol + oleate
show the reaction diagram
-
chromogenic detection using 5,5'-dithio-bis-(2-nitrobenzoic acid) as chromogen or the 6-methylresorufin ester of 1-O,2-dilauryl-rac-glycero-3-glutaric acid, substrate synthesis, assay development, optimization, and method comparison, overview
-
-
?
4-nitrophenyl laurate + H2O
4-nitrophenol + laurate
show the reaction diagram
diolein + H2O
monoolein + oleate
show the reaction diagram
-
-
-
-
?
L-alpha-phosphatidylcholine + H2O
?
show the reaction diagram
-
-
-
-
?
olive oil + H2O
?
show the reaction diagram
-
-
-
-
?
triacylglycerol + H2O
diacylglycerol + a carboxylate
show the reaction diagram
tributyrin + H2O
?
show the reaction diagram
-
-
-
-
?
tributyrin + H2O
butyric acid + ?
show the reaction diagram
-
-
-
-
?
tributyrin + H2O
dibutyrin + butyrate
show the reaction diagram
tricaprylin + H2O
dicaprylin + caprylate
show the reaction diagram
-
-
-
-
?
trioctanoin + H2O
dioctanoin + octanoate
show the reaction diagram
-
-
-
-
?
trioctanoin + H2O
octanoic acid + ?
show the reaction diagram
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-
-
-
?
triolein + H2O
diolein + oleate
show the reaction diagram
trioleoylglycerol + H2O
oleic acid + ?
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
4-nitrophenyl laurate + H2O
4-nitrophenol + laurate
show the reaction diagram
-
recombinant enzyme in Sf9 cells
-
?
triacylglycerol + H2O
diacylglycerol + a carboxylate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Colipase
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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activates the phospholipase A1 activity of the enzyme, overview
Mg2+
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NaCl
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-hexadecenoic acid
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aurantiamide
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Bile salts
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cnidiadin
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orlistat
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sodium taurodeoxycholate
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-
additional information
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changes in HDL cholesteryl ester and fatty acid content have no effect on hepatic lipase displacement, increases in HDL phospholipid and TG content significantly inhibit hepatic lipase displacement
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
bile salt
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pancreatic lipase, stimulation
CGI-58
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Colipase
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dilinoleoylphosphatidylcholine
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promotes hepatic lipase liberation from cell surface proteoglycans
HDL
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HDL is able to displace cell surface-bound hepatic lipase and stimulate vascular triglyceride hydrolysis, much like heparin. HDL fractions from hyperlipidemic patients are unable to displace HL from the cell surface
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heparin
high-density lipoprotein
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HDL, acts much like heparin to liberate hepatic lipase from cell surface proteoglycans and stimulate triglyceride clearance
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perilipin A
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phosphorylation of perilipin specifically at serine 517 by protein kinase A is essential for ATGL activation, overview
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sodium taurodeoxycholate
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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kinetics of beta5'-loop-mediated interaction of the enzyme with the colipase, overview
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.08
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purified recombinant mutant enzyme lacking the cap domain, substrate triolein
0.5
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purified recombinant mutant enzyme lacking the lid domain, substrate triolein
15
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purified pancreatic lipase, solid meal
30
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purified recombinant wild-type enzyme, substrate triolein
32
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purified gastric lipase, liquid test meal
34
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purified gastric lipase, solid test meal
43
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purified pancreatic lipase, liquid meal
51.1
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550
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purified recombinant enzyme in presence of colipase at pH 8.8
1300
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purified gastric lipase, substrate tributyrin
3900
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purified recombinant wild-type enzyme
7895
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8000
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purified pancreaic lipase, substrate tributyrin
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5
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gastric lipase HGL, assay at
5
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assay at
6.5 - 7.5
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pancreatic lipase HPL
7
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assay at
8 - 9
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8
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assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8
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-
additional information
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pH profiles of the recombinant enzyme, overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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gastric lipase HGL
Manually annotated by BRENDA team
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i.e. RH-17777 cell, large cell lung carcinoma cell line, low enzyme activity
Manually annotated by BRENDA team
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HSL
Manually annotated by BRENDA team
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ATGL is highly expressed in the pigment epithelium and can be found on the plasma membrane
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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mainly
Manually annotated by BRENDA team
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secretion in the stomach
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Manually annotated by BRENDA team
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ATGL in the pigment epithelium
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10000
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colipase
32000
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x * 47000, wild-type enzyme, SDS-PAGE, x * 43000, lid domain lacking mutant, SDS-PAGE, x * 32000, cap domain lacking mutant, SDS-PAGE
43000
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x * 47000, wild-type enzyme, SDS-PAGE, x * 43000, lid domain lacking mutant, SDS-PAGE, x * 32000, cap domain lacking mutant, SDS-PAGE
47000
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x * 47000, wild-type enzyme, SDS-PAGE, x * 43000, lid domain lacking mutant, SDS-PAGE, x * 32000, cap domain lacking mutant, SDS-PAGE
48000
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x * 48000, SDS-PAGE
49946
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x * 50000, recombinant enzyme, SDS-PAGE, x * 52343, recombinant glycosylated enzyme, mass spectrometry, x * 49946, recombinant nonglycosylated enzyme, mass spectrometry
52343
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x * 50000, recombinant enzyme, SDS-PAGE, x * 52343, recombinant glycosylated enzyme, mass spectrometry, x * 49946, recombinant nonglycosylated enzyme, mass spectrometry
67000
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x * 67000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
phosphoprotein
side-chain modification
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contains approximately 8% carbohydrate
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
from liver microsomes
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heparin-Sepharose column chromatography
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recombinant from Sf9 insect cells, about 30fold
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recombinant secreted enzyme from protease A-deficient Pichia pastoris strain culture supernatant by cation and anion exchange chromatography to homogeneity
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recombinant wild-type and mutant enzymes from insect cells, mutant lacking the cap domain is only stable at acidic pH value during purification
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recombinant wild-type and mutant enzymes from Pichia pastoris
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression in Escherichia coli M15 with a N-terminal His-tagged substituting the signal sequence, the expressed protein is insoluble and inactive, expression of the C-terminally His-tagged enzyme containing its native signal sequence in Spodoptera frugiperda Sf9 insect cells via baculovirus infection results in active enzyme
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expressed in COS-7 cells
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expressed in Pichia pastoris
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expressed in Pichia pastoris strain GS115 and Sf21 insect cells
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expression in Pichia pastoris, best expression is obtained by replacing the native signal peptide with a yeast signal peptide
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expression of PLRP2 in the protease A-deficient yeast Pichia pastoris as secreted enzyme
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expression of wild-type and mutant enzymes in Pichia pastoris
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expression of wild-type enzyme and mutants lacking the cap and the lid domain via baculovirus transfection in insect cells
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functional expression of wild-type and C-terminally truncated or non-glycosylated secreted mutant enzymes in RH-17777 cells
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the genes encoding the enzyme are located on chromosome 16 within a cluster of carboxylesterase genes, genetic organization, expression analysis
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the HSL gene is located on chromosome 19q13.2. The ATGL gene PNPLA2 span 6.32 kb of genomic DNA, which are located on chromosome 11p15.5
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
mRNA and protein levels are reduced in obese patients with insulin resistance
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E250Q
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site-directed mutagenesis, the mutant shows reduced triacylglyceride lipase activity compared to the wild-type endothelial lipase
FS270
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mutant exhibits increased activity (2.0fold more active compared to the wild type enzyme)
FS282
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mutant exhibits increased activity (7.6fold more active compared to the wild type enzyme)
G241R
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site-directed mutagenesis, the mutant shows reduced triacylglyceride lipase activity compared to the wild-type endothelial lipase
H151A
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mutant shows changed pH-activity profile and reduced lipase activity compared to the wild type enzyme
I408D
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site-directed mutagenesis, reduced activity, altered substrate specificity, and increased lag time compared to the wild-typ enzyme, water-accessible surface area of the beta5'-loop compared to the wild-type enzyme's loop
I408K
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site-directed mutagenesis, reduced activity, altered substrate specificity, and increased lag time compared to the wild-typ enzyme, water-accessible surface area of the beta5'-loop compared to the wild-type enzyme's loop
K80E
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mutant shows changed pH-activity profile and reduced lipase activity compared to the wild type enzyme
L264E
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mutant shows changed pH-activity profile and reduced lipase activity compared to the wild type enzyme
L412D
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site-directed mutagenesis, slightly reduced activity compared to the wild-typ enzyme, water-accessible surface area of the beta5'-loop compared to the wild-type enzyme's loop
L412K
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site-directed mutagenesis, slightly reduced activity compared to the wild-typ enzyme, water-accessible surface area of the beta5'-loop compared to the wild-type enzyme's loop
N79Q
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site-directed mutagenesis, disruption of N-glycosylation site, the N-glycosylation at Asn70 is not required for activity
P195L
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the mutant exhibits reduced activity and is associated with neutral lipid storage disease that is characterized by systemic triglycerol accumulation and myopathy
Q289X
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mutant exhibits increased activity (24.6fold more active compared to the wild type enzyme)
S152G
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inactive mutant, the inactive enzyme mutant S152G binds to tricaprylin in a water emulsion interface competiting with the active enzyme hydrolyzing the substrate, overview
T372A
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the mutation gives a protein that binds lipid droplets and functions the same as the wild type protein
V407D
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site-directed mutagenesis, reduced activity, altered substrate specificity, and increased lag time compared to the wild-typ enzyme, water-accessible surface area of the beta5'-loop compared to the wild-type enzyme's loop
V407K
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site-directed mutagenesis, reduced activity, altered substrate specificity, and increased lag time compared to the wild-typ enzyme, water-accessible surface area of the beta5'-loop compared to the wild-type enzyme's loop
Y114F
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mutant shows changed pH-activity profile and reduced lipase activity compared to the wild type enzyme
additional information