Information on EC 3.1.1.79 - hormone-sensitive lipase and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.1.1.79
-
RECOMMENDED NAME
GeneOntology No.
hormone-sensitive lipase
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
triacylglycerol degradation
-
-
lipid metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
diacylglycerol acylhydrolase
This enzyme is a serine hydrolase. Compared with other lipases, hormone-sensitive lipase has a uniquely broad substrate specificity. It hydrolyses all acylglycerols (triacylglycerol, diacylglycerol and monoacylglycerol) [2,3,4] as well as cholesteryl esters [2,4], steroid fatty acid esters [5], retinyl esters [6] and p-nitrophenyl esters [4,7]. It exhibits a preference for the 1- or 3-ester bond of its acylglycerol substrate compared with the 2-ester bond [8]. The enzyme shows little preference for the fatty acids in the triacylglycerol, although there is some increase in activity with decreasing chain length. The enzyme activity is increased in response to hormones that elevate intracellular levels of cAMP.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-62-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
enzyme expression is abolished in the slit-skin smear specimens from patients with lepromatous and borderline leprosy caused by Mycobacterium leprae, which suppresses lipid degradation through inhibition of enzyme expression
physiological function
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-dioleoyl-sn-glycerol + H2O
2-oleylglycerol + oleate
show the reaction diagram
-
-
-
-
?
1,2-dioleoyl-sn-glycerol + H2O
?
show the reaction diagram
-
-
-
-
?
cholesteryl oleate + H2O
?
show the reaction diagram
-
-
-
-
?
cholesteryl oleate + H2O
cholesterol + oleate
show the reaction diagram
-
-
-
-
?
diacylglycerol + H2O
monoacylglycerol + a carboxylate
show the reaction diagram
-
-
-
-
?
dioleoyl glycerol + H2O
monooleoylglycerol + oleate
show the reaction diagram
-
21% of activity with vinylbutyrate
-
-
?
lipid emulsion + H2O
fatty acids
show the reaction diagram
-
recombinant HSL, the release of fatty acids is only slightly affected by their degree of unsaturation
fatty acids ranging in chain length from 12 to 24 carbon atoms and in unsaturation from 0 to 6 double bonds
-
?
olive oil + H2O
?
show the reaction diagram
-
3% of activity with vinylbutyrate
-
-
-
p-nitrophenyl butyrate + H2O
p-nitrophenol + butanoate
show the reaction diagram
-
-
-
-
?
rac 1,2(2,3)-sn diolein + H2O
?
show the reaction diagram
-
-
-
-
?
triacylglycerol + H2O
diacylglycerol + a carboxylate
show the reaction diagram
-
-
-
-
?
tributanoyl glycerol + H2O
dibutanoylglycerol + butanoate
show the reaction diagram
-
8% of activity with vinylbutyrate
-
-
?
tributanoylglycerol + H2O
dibutanoylglycerol + butanoate
show the reaction diagram
-
-
-
-
?
tributyrin + H2O
dibutanoylglycerol + butanoate
show the reaction diagram
-
-
-
-
?
trioctanoin + H2O
dioctanoylglycerol + octanoate
show the reaction diagram
-
-
-
-
?
trioctanoyl glycerol + H2O
dioctanoylglycerol + octanoate
show the reaction diagram
-
3% of activity with vinylbutyrate
-
-
?
trioleoylglycerol + H2O
?
show the reaction diagram
-
-
-
-
?
trioleoylglycerol + H2O
dioleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
tripropionin + H2O
dipropanoylglycerol + propanoate
show the reaction diagram
-
-
-
-
?
tripropionyl glycerol + H2O
dipropionylglycerol + propionate
show the reaction diagram
-
4% of activity with vinylbutyrate
-
-
?
vinyl acetate + H2O
acetate + ethylenol
show the reaction diagram
-
-
-
-
?
vinyl acetate + H2O
vinyl alcohol + acetate
show the reaction diagram
-
67% of activity with vinylbutyrate
-
-
?
vinyl butyrate + H2O
butanoate + ethylenol
show the reaction diagram
-
-
-
-
?
vinyl butyrate + H2O
vinyl alcohol + butanoate
show the reaction diagram
-
-
-
-
?
vinyl laurate + H2O
laurate + ethylenol
show the reaction diagram
-
-
-
-
?
vinyl laurate + H2O
vinyl alcohol + laurate
show the reaction diagram
-
15% of activity with vinylbutyrate
-
-
?
vinyl propionate + H2O
propanoate + ethylenol
show the reaction diagram
-
-
-
-
?
vinyl propionate + H2O
vinyl alcohol + propionate
show the reaction diagram
-
50% of activity with vinylbutyrate
-
-
?
additional information
?
-
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
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3,4-dihydro-1H-isoquinolin-2-yl)-carbamic acid 4-tert-butoxycarbonylamino-phenyl ester
-
IC50: 3 nM
(S)-4-isopropyl-3-methyl-2-[3-methylpiperidine-1-carbonyl]isoxazol-5[2H]-one
-
-
2-methoxyphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
-
IC50: 6400 nM
3-(3,5-dichlorophenyl)-N,N-dimethyl-5-(methylsulfanyl)-1H-1,2,4-triazole-1-carboxamide
-
-
3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-ethoxy-1,3,4-oxadiazol-2(3H)-one
-
-
3-(4-chlorophenyl)-N,N-dimethyl-5-(methylsulfanyl)-1H-1,2,4-triazole-1-carboxamide
-
-
4-(acetylamino)phenyl morpholin-4-ylcarbamate
-
-
4-(butyrylamino)phenyl morpholin-4-ylcarbamate
-
IC50: 3200 nM
4-benzoylphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
-
-
4-benzylphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
-
IC50: 97 nM
4-chlorophenyl (1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)carbamate
-
IC50: 32 nM
4-chlorophenyl (3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)carbamate
-
IC50: 35 nM
4-chlorophenyl 2,2-bis(2-ethoxyethyl)hydrazinecarboxylate
-
IC50: 184 nM
4-chlorophenyl 2,2-dipentylhydrazinecarboxylate
-
IC50: 50 nM
4-chlorophenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
-
IC50: 19 nM
4-isopropyl-3-methyl-2-[piperidine-1-carbonyl]isoxazol-5[2H]-one
-
-
4-methoxyphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
-
IC50: 360 nM
4-[(2,2-dimethylpropanoyl)amino]phenyl morpholin-4-ylcarbamate
-
IC50: 47 nM
4-[(cyclohexylcarbonyl)amino]phenyl morpholin-4-ylcarbamate
-
IC50: 10 nM
benzyl (4-(5-methoxy-2-oxo-1,3,4-oxadiazol-3(2H)-yl)-2-methylphenyl)carbamate
-
-
benzyl (4-[[(morpholin-4-ylamino)carbonyl]oxy]phenyl)acetate
-
IC50: 5 nM
Diethyl p-nitrophenyl phosphate
-
100fold molar excess, complete inactivation after 15 min
diethyl-p-nitrophenyl phosphate
-
0.1 mM, 94% inhibition
diisopropyl fluorophosphate
ethyl (4-[[(morpholin-4-ylamino)carbonyl]oxy]phenyl)acetate
-
IC50: 138 nM
Hg2+
-
0.1 mM, 91% inhibition
HgCl2
-
0.1 mM, 93% inhibition
methyl 4-[[(3,4-dihydroisoquinolin-2(1H)-ylamino)carbonyl]oxy]benzoate
-
IC50: 9952 nM
morpholin-4-yl-carbamic acid 4-[(4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester
-
IC50: 1 nM
N',N'-bis-(2-butylamino-ethyl)-hydrazinecarboxylic acid 4-chloro-phenyl ester
-
IC50: 24 nM
N',N'-bis-[2-(ethyl-methyl-amino)-ethyl]-hydrazinecarboxylic acid 4-chloro-phenyl ester
-
IC50: 515 nM
phenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
-
IC50: 205 nM
phenylmethylsulfonyl fluoride
-
100fold molar excess, complete inactivation after 15 min
additional information
-
hormone-sensitive lipase is knocked down by RNA interference or selectively inhibited
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.4
tributanoyl glycerol
-
37°C, pH 8.0
0.4
tributyrin
-
-
15
tripropionin
-
-
15
tripropionyl glycerol
-
37°C, pH 8.0
170 - 315
vinyl acetate
10 - 25
vinyl butyrate
4
vinyl laurate
-
-
70 - 75
vinyl propionate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
190
p-nitrophenyl butyrate
-
-
18
tributyrin
-
-
6
trioctanoin
-
-
7
tripropionin
-
-
170
vinyl acetate
-
-
625
vinyl butyrate
-
-
375
vinyl laurate
-
-
800
vinyl propionate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000003
(3,4-dihydro-1H-isoquinolin-2-yl)-carbamic acid 4-tert-butoxycarbonylamino-phenyl ester
Homo sapiens;
-
IC50: 3 nM
0.000005
(S)-4-isopropyl-3-methyl-2-[3-methylpiperidine-1-carbonyl]isoxazol-5[2H]-one
Homo sapiens;
-
-
0.0064
2-methoxyphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
Homo sapiens;
-
IC50: 6400 nM
0.000008
3-(4-chlorophenyl)-N,N-dimethyl-5-(methylsulfanyl)-1H-1,2,4-triazole-1-carboxamide
Homo sapiens;
-
-
0.0032
4-(butyrylamino)phenyl morpholin-4-ylcarbamate
Homo sapiens;
-
IC50: 3200 nM
0.000097
4-benzylphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
Homo sapiens;
-
IC50: 97 nM
0.000032
4-chlorophenyl (1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)carbamate
Homo sapiens;
-
IC50: 32 nM
0.000035
4-chlorophenyl (3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)carbamate
Homo sapiens;
-
IC50: 35 nM
0.000184
4-chlorophenyl 2,2-bis(2-ethoxyethyl)hydrazinecarboxylate
Homo sapiens;
-
IC50: 184 nM
0.00005
4-chlorophenyl 2,2-dipentylhydrazinecarboxylate
Homo sapiens;
-
IC50: 50 nM
0.000019
4-chlorophenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
Homo sapiens;
-
IC50: 19 nM
0.00036
4-methoxyphenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
Homo sapiens;
-
IC50: 360 nM
0.000047
4-[(2,2-dimethylpropanoyl)amino]phenyl morpholin-4-ylcarbamate
Homo sapiens;
-
IC50: 47 nM
0.00001
4-[(cyclohexylcarbonyl)amino]phenyl morpholin-4-ylcarbamate
Homo sapiens;
-
IC50: 10 nM
0.000005
benzyl (4-[[(morpholin-4-ylamino)carbonyl]oxy]phenyl)acetate
Homo sapiens;
-
IC50: 5 nM
0.000138
ethyl (4-[[(morpholin-4-ylamino)carbonyl]oxy]phenyl)acetate
Homo sapiens;
-
IC50: 138 nM
0.009952
methyl 4-[[(3,4-dihydroisoquinolin-2(1H)-ylamino)carbonyl]oxy]benzoate
Homo sapiens;
-
IC50: 9952 nM
0.000001
morpholin-4-yl-carbamic acid 4-[(4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester
Homo sapiens;
-
IC50: 1 nM
0.000024
N',N'-bis-(2-butylamino-ethyl)-hydrazinecarboxylic acid 4-chloro-phenyl ester
Homo sapiens;
-
IC50: 24 nM
0.000515
N',N'-bis-[2-(ethyl-methyl-amino)-ethyl]-hydrazinecarboxylic acid 4-chloro-phenyl ester
Homo sapiens;
-
IC50: 515 nM
0.000205
phenyl 3,4-dihydroisoquinolin-2(1H)-ylcarbamate
Homo sapiens;
-
IC50: 205 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00059
women
0.00062
men
1.2
-
specific activity of the purified wild type enzyme against trioleoylglycerol
2.3
-
specific activity of the purified wild type enzyme against cholesteryl oleate
23
-
specific activity of the purified wild type enzyme against 1,2-dioleoyl-sn-glycerol
50
-
specific activity of the purified wild type enzyme against p-nitrophenylbutyrate
143
-
hydrolysis of vinyl butyrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
HEK-293 fibroblasts stably expressing fatty acid transport protein 1
Manually annotated by BRENDA team
-
activity is similar in untrained and trained skeletal muscles both before and after prolonged exercise
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
containing hormone-sensitive lipase. In response to insulin the enzyme is translocated to the cytosol
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
84032
-
x * 84032, deduced from nucleotide sequence
88000
-
x * 88000, SDS-PAGE
88200
-
x * 88200, SDS-PAGE, immunoblot
116000
-
x * 116000, SDS-PAGE, testis HSL
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 84000, SDS-PAGE, recombinant HSL
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion exchange chromatography followed by nickel affinity chromatography and dialysis
-
partially purified, Q-Sepharose FF
-
recombinant HSL
-
recombinant human HSL from baculovirus-infected insect cells
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of cDNA
-
expression Sf9 insect cells
-
five C-terminally His-tagged human HSL variants are successfully cloned and expressed in Sf9 insect cells using the baculovirus/insect cell expression system
-
human HSL is expressed from baculovirus-infected insect cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
infection by live Mycobacterium leprae significantly suppresses the enzyme expression levels. This suppression is not observed with dead Mycobacterium leprae or latex bead controls
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S552A/S554A
-
variant AVA-SS, no effect on the activity
S552E/S554E
-
variant AVA-AA, decreasing activity of human HSL against trioleoylglycerol, 1,2-dioleoyl-sn-glycerol and cholesteryl oleate substrates by 67%, 63% and 60%, respectively. The activity against p-nitrophenylbutyrate also decreases, but only by 30% compared to wild type HSL
S554A
-
variant SVA-SS, resulted in a slight decrease in lipolytic activity
S554E
-
variant SVE-SS, resulted in similar to wild type activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
monitoring of enzyme mRNA levels in slit-skin smear specimens from patients with lepromatous and borderline leprosy may be a useful indicator of patient prognosis
medicine
-
inhibition of hormone-sensitive lipase may improve insulin sensitivity and blood glucose handling in type 2 diabetes. The utility of enzyme inhibition in diabetes treatment will depend on the presence or absence of adverse effects of inhibition in tissues beyond the adipocyte