Information on EC 3.1.1.79 - hormone-sensitive lipase

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

EC NUMBER
COMMENTARY hide
3.1.1.79
-
RECOMMENDED NAME
GeneOntology No.
hormone-sensitive lipase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
diacylglycerol + H2O = monoacylglycerol + a carboxylate
show the reaction diagram
-
-
-
-
monoacylglycerol + H2O = glycerol + a carboxylate
show the reaction diagram
-
-
-
-
triacylglycerol + H2O = diacylglycerol + a carboxylate
show the reaction diagram
-
-
-
-
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
a Leydig tumor strain
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
SSO2517 can be expressed as SsoNDELTA or SsoNDELTAlong (longer version of SsoNDELTA with an extended N-terminus)
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
E2JFF5, E2JFF6
phylogentic analysis suggests that the two HSL isozymes derive from paralogous genes that may have arisen during a teleost-specific genome duplication event; phylogentic analysis suggests that the two HSL isozymes derive from paralogous genes that may have arisen during a teleost-specific genome duplication event
malfunction
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-dioleoyl-sn-glycerol + H2O
2-oleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
1,2-dioleoyl-sn-glycerol + H2O
2-oleylglycerol + oleate
show the reaction diagram
1,2-dioleoyl-sn-glycerol + H2O
?
show the reaction diagram
1,2-dioleoylglycerol + H2O
2-oleoylglycerol + oleate
show the reaction diagram
-
-
mayor end product of trioleoylglycerol and 1,2-dioleoylglycerol hydrolysis
-
?
1-monooleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
3times higher activity than with 2-oleoylglycerol
-
-
?
1-naphthyl acetate + H2O
1-naphthol + acetate
show the reaction diagram
-
-
-
-
?
2-monooleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
-
-
-
?
2-naphthyl acetate + H2O
2-naphthol + acetate
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl acetate + H2O
4-methylumbelliferol + acetate
show the reaction diagram
-
-
-
?
4-nitrophenyl acetate + H2O
4-nitrophenol + acetate
show the reaction diagram
4-nitrophenyl butyrate + H2O
4-nitrophenol + butyrate
show the reaction diagram
4-nitrophenyl butyrate + H2O
?
show the reaction diagram
-
-
-
-
?
4-nitrophenyl caproate + H2O
4-nitrophenol + acetate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl caproate + H2O
?
show the reaction diagram
-
-
-
-
?
4-nitrophenyl pentanoate + H2O
4-nitrophenol + pentanoate
show the reaction diagram
alpha-naphtyl acetate + H2O
?
show the reaction diagram
-
-
-
-
?
cholesterol oleate + H2O
cholesterol + oleate
show the reaction diagram
-
-
-
-
?
cholesteryl ester + H2O
cholesterol + a carboxylate
show the reaction diagram
cholesteryl oleate + H2O
?
show the reaction diagram
-
-
-
-
?
cholesteryl oleate + H2O
cholesterol + oleate
show the reaction diagram
cholesteryl oleate + H2O
cholesterol + oleic acid
show the reaction diagram
-
-
-
-
?
dehydroepiandrosterone oleate + H2O
dehydroepiandrosterone + oleate
show the reaction diagram
-
12.9% of activity with 1-oleoyl-2-oleylglycerol
-
-
?
diacylglycerol + H2O
monoacylglycerol + a carboxylate
show the reaction diagram
dioleoyl glycerol + H2O
monooleoylglycerol + oleate
show the reaction diagram
-
21% of activity with vinylbutyrate
-
-
?
dioleoylglycerol + H2O
monooleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
dioleoylglycerol + H2O
oleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
estradiol-17-beta-oleate + H2O
17-beta-estradiol + oleate
show the reaction diagram
-
17.9% of activity with 1-oleoyl-2-oleylglycerol
-
-
?
estradiol-17-beta-palmitate + H2O
17-beta-estradiol + palmitate
show the reaction diagram
-
18.3% of activity with 1-oleoyl-2-oleylglycerol
-
-
?
lipid emulsion + H2O
fatty acids
show the reaction diagram
monoacylglycerol + H2O
glycerol + a carboxylate
show the reaction diagram
oleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
-
-
-
?
olive oil + H2O
?
show the reaction diagram
-
3% of activity with vinylbutyrate
-
-
-
p-nitrophenyl acetate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl acetate + H2O
p-nitrophenol + acetate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl butyrate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl butyrate + H2O
p-nitrophenol + butanoate
show the reaction diagram
p-nitrophenyl caprylate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl carproate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl decanoate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl hexanoate + H2O
p-nitrophenol + hexanoate
show the reaction diagram
SsoNDELTAlong, is 15fold more active with the substrate p-nitrophenyl hexanoate than SsoNDELTA
-
-
?
p-nitrophenyl laurate + H2O
p-nitrophenol + laurate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl palmitate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl palmitate + H2O
p-nitrophenol + palmitate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl stearate + H2O
?
show the reaction diagram
using various p-nitrophenyl esters as substrates. Enzyme efficiently hydrolyzes p-nitrophenyl acetate (75%), p-nitrophenyl butyrate (100%), p-nitrophenyl carproate (55%) and p-nitrophenyl caprylate (50%), a lower level of hydrolysis is observed for p-nitrophenyl decanoate (25%), p-nitrophenyl palmitate (2%) and p-nitrophenyl stearate (2%)
-
-
?
p-nitrophenyl-dodecanoate + H2O
p-nitrophenol + dodecanoate
show the reaction diagram
SsoNDELTA shows 4.4fold lower activity than SsoNDELTAlong with p-nitrophenyl-dodecanoate as substrate
-
-
?
rac 1,2(2,3)-sn diolein + H2O
?
show the reaction diagram
-
-
-
-
?
testosterone oleate + H2O
testosterone + oleate
show the reaction diagram
-
1.4% of activity with 1-oleoyl-2-oleylglycerol
-
-
?
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
-
-
-
-
?
tributyrylglycerol + H2O
?
show the reaction diagram
SsoNDELTA shows 6old lower activity than SsoNDELTAlong with glyceryl tributyrate as substrate
-
-
?
tridecanoylglycerol + H2O
?
show the reaction diagram
SsoNDELTA shows 4.7fold higher activity than SsoNDELTAlong with glyceryl tridecanoate as substrate
-
-
?
trihexanoylglycerol + H2O
?
show the reaction diagram
SsoNDELTA shows 4fold lower activity than SsoNDELTAlong with glyceryl trihexanoate as substrate
-
-
?
trioctanoin + H2O
dioctanoylglycerol + octanoate
show the reaction diagram
-
-
-
-
?
trioctanoyl glycerol + H2O
dioctanoylglycerol + octanoate
show the reaction diagram
-
3% of activity with vinylbutyrate
-
-
?
trioctanoylglycerol + H2O
?
show the reaction diagram
SsoNDELTA shows 1.7fold lower activity than SsoNDELTAlong with glyceryl trioctanoate as substrate
-
-
?
triolein + H2O
1,2-dioleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
triolein + H2O
diolein + oleate
show the reaction diagram
triolein + H2O
dioleoylglycerol + oleate
show the reaction diagram
trioleoylglycerol + H2O
1,2-dioleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
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
1,2-dioleoylglycerol + H2O
2-oleoylglycerol + oleate
show the reaction diagram
-
-
mayor end product of trioleoylglycerol and 1,2-dioleoylglycerol hydrolysis
-
?
1-monooleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
3times higher activity than with 2-oleoylglycerol
-
-
?
2-monooleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
-
-
-
?
cholesteryl ester + H2O
cholesterol + a carboxylate
show the reaction diagram
-
-
-
-
?
cholesteryl oleate + H2O
cholesterol + oleate
show the reaction diagram
-
-
-
-
?
diacylglycerol + H2O
monoacylglycerol + a carboxylate
show the reaction diagram
dioleoylglycerol + H2O
oleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
monoacylglycerol + H2O
glycerol + a carboxylate
show the reaction diagram
oleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
-
-
-
?
triacylglycerol + H2O
diacylglycerol + a carboxylate
show the reaction diagram
trioleoylglycerol + H2O
1,2-dioleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
trioleoylglycerol + H2O
dioleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
10 M, 40% stimulation
KCl
-
enhances activity
NaCl
-
enhances activity
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
2-propanol
-
80-90% inhibition
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
76-0079
-
a commercial small molecule inhibitor
-
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
betaine
-
it enhances the enzyme activity 2fold at 50C and 3 M, and 1.5fold at 45C and 1-3 M, while it reduces the enzyme activity at 35-40C, by 20% at 40C and 3 M,about % at 1 M, overview
CaCl2
-
50 mM, 47% inhibition
CAY10499
-
-
CoCl2
-
10 mM, 34% inhibition
Cu2+
-
10 mM, 50-60% inhibition
Diethyl p-nitrophenyl phosphate
-
100fold molar excess, complete inactivation after 15 min
diethyl-p-nitrophenyl phosphate
-
0.1 mM, 94% inhibition
diisopropyl fluorophosphate
diisopropylfluorophosphate
Emulgen 120
-
0.1%, 955 of cholesteryl oleate hydrolysis
ethanol
-
80-90% inhibition
ethyl (4-[[(morpholin-4-ylamino)carbonyl]oxy]phenyl)acetate
-
IC50: 138 nM
HgCl2
L-cysteine
-
inhibits the enzyme activity in presence of TNF-alpha
L-cystine
-
inhibits the enzyme activity in presence of TNF-alpha
L-methionine
-
L-methionine enhances the enzyme activaty in absence of tumor necrosis factor-alpha, but inhibits it in presence of TNF-alpha
methanol
-
80-90% inhibition
methyl 4-[[(3,4-dihydroisoquinolin-2(1H)-ylamino)carbonyl]oxy]benzoate
-
IC50: 9952 nM
MgCl2
-
50 mM, 52% inhibition
MnCl2
-
50 mM, 45% inhibition
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
phenylmethanesulfonyl fluoride
-
0.01 mM, approx. 75% inhibition, 0.01 mM, approx. 90% inhibition
phenylmethylsulfonyl fluoride
-
100fold molar excess, complete inactivation after 15 min
proline
-
inhibits the enzyme at 35-50C and concentrations of 1-3 M
SDS
-
above 2 mM. Inhibition by SDS is partially reversed by Triton X-100
Trimethylamine N-oxide
-
it enhances the enzyme activity 2.5fold at 50C and 3 M, and 5fold at 45C and 1 M, while it reduces the enzyme activity at 35-40C, by 60% at 40C and 3 M, 10% at 1 M, overview
Triton X-100
-
above 0.1%
Tween 20
-
inhibits from 0.1 to 2.0%
ZnCl2
-
44% inhibition at 10 mM, 99% inhibition at 50 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
betaine
-
it enhances the enzyme activity 2fold at 50C and 3 M, and 1.5fold at 45C and 1-3 M, while it reduces the enzyme activity at 35-40C, by 20% at 40C and 3 M, about 5% at 1 M, overview
cyclic AMP-dependent protein kinase
-
phosphorylation, 40% activation of triolein hydrolyzing activity
-
HSL inhibitor
-
reduced activity in macrophage foam cells due to increased activity of an inhibitor protein
-
L-methionine
-
L-methionine enhances the enzyme activity in absence of tumor necrosis factor-alpha, but inhibits it in presence of TNF-alpha
phosphatidylcholine
-
0.075 mM, slight activation upon incorporation into cholestryl oleate liquid crystals
phosphatidylethanolamine
-
0.075 mM, approx. 6fold activation upon incorporation into cholestryl oleate liquid crystals
Phospholipid
-
-
potassium acetate
-
enhances activity
SDS
-
slight stimulation up to 2 mM
Sodium acetate
-
enhances activity
testosterone
-
left ventricle HSL activity against triglycerides is significantly elevated in intact rats supplemented with testosterone, testosterone replacement fully reverses this effect
Trimethylamine N-oxide
-
it enhances the enzyme activity 2.5fold at 50C and 3 M, and 5fold at 45C and 1 M, while it reduces the enzyme activity at 35-40C, by 60% at 40C and 3 M, 10% at 1 M, overview
trimyrestoyl glycerol
-
3.7fold increase of triolein hydrolysis rate
tripalmitoyl glycerol
-
2.1fold increase of triolein hydrolysis rate
tristearoyl glycerol
-
1.9fold increase of triolein hydrolysis rate
Triton X-100
-
0.1%, stimulates
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.033
1,2-dioleoylglycerol
-
37C
0.54
1-naphthyl acetate
-
Vmax: 0.019 mM/min
5.43
2-naphthyl acetate
-
Vmax: 0.0168 mM/min
0.28 - 7.42
4-nitrophenyl acetate
0.54
Alpha-naphtyl acetate
-
Vmax: 0.019 mM/min
0.0022 - 0.025
cholesteryl oleate
0.011 - 0.099
cholesteyl oleate
0.03
dioleoylglycerol
-
37C, pH 7.0
0.28 - 7.42
p-nitrophenyl acetate
0.164 - 1.06
p-nitrophenyl butyrate
0.03 - 0.054
p-nitrophenyl hexanoate
0.268 - 0.462
p-nitrophenyl oleate
0.4
tributanoyl glycerol
-
37C, pH 8.0
0.4
tributyrin
-
-
0.0034
trioleoylglycerol
-
37C, pH 7.0
15
tripropionin
-
-
15
tripropionyl glycerol
-
37C, 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
-
-
2.5 - 34.5
p-nitrophenyl hexanoate
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
0.068
-
cholesteryl oleate hydroylsis
0.3
-
hydrolysis of estradiol-17-beta-oleate
0.8
-
hydrolysis of p-nitrophenyl laurate
0.9
-
hydrolysis of p-nitrophenyl palmitate
1.2
-
specific activity of the purified wild type enzyme against trioleoylglycerol
1.45
-
hydrolysis of cholesteryl oleate
2.3
-
specific activity of the purified wild type enzyme against cholesteryl oleate
2.6
-
hydrolysis of 1-oleoyl-2-oleylglycerol
2.8
-
1-oleoyl-2-oleylglycerol
3.8
-
hydrolysis of cholesteryl oleate
4.7
-
hydrolysis of p-nitrophenyl acetate
22
-
hydrolysis of p-nitrophenyl butyrate
23
-
specific activity of the purified wild type enzyme against 1,2-dioleoyl-sn-glycerol
30
-
hydrolysis of 1-oleoyl-2-O-oleylglycerol
50
-
specific activity of the purified wild type enzyme against p-nitrophenylbutyrate
143
-
hydrolysis of vinyl butyrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
SsoNDELTAlong, substrate: p-nitrophenyl hexanoate
7.5
-
optimal activity
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5 - 7.5
pH 4.5: 80% of maximal activity, pH 7.5: about 65% of maximal activity, substrate: p-nitrophenyl hexanoate, SsoNDELTAlong
5 - 9
-
approx. 50% of maximal activity at pH 5.5 and pH 8.5, respectively
7 - 10
-
pH 7: about 60% of maximal activity, pH 10.: about 50% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
-
activity increases with temperature reaching a plateau at 55C
85
substrate: p-nitrophenyl hexanoate, SsoNDELTAlong
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 35
-
activity range, enzyme without additives
25 - 50
-
25C: about 90% of maximal activity, 50C: about 40% of maximal activity
70 - 90
70C: substrate: about 75% of maximal activity, 90C: about 90% of maximal activity, p-nitrophenyl hexanoate, SsoNDELTAlong
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
HEK-293 fibroblasts stably expressing fatty acid transport protein 1
Manually annotated by BRENDA team
-
postmeiotic germ cells express a specific HSL isoform that includes a 313 amino acid N-terminus encoded by a testis-specific exon T1
Manually annotated by BRENDA team
shows HSL staining in cytoplasm during proestrus and estrus, in the nucleus during metestrus, and in cytoplasm and the nucleus during diestrus
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
-
cotyledon
Manually annotated by BRENDA team
-
HSL accounts for the entire neutral cholesteryl ester hydrolase activity of enterocytes
Manually annotated by BRENDA team
HSL is found in the epithelial cells nuclei
Manually annotated by BRENDA team
additional information
granulosa cells and oocytes of primordial follicles are immunonegative; HSL expression in theca cells and oocytes decrease during follicular atresia
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
HSL is located in the epithelial cells nuclei and in the cilia during proestrus and estrus but mainly in the nucleus during metestrus and diestrus
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38500
-
calculated from cDNA
38600
-
SDS-PAGE
43000
HSL-immunoreactive bands at 84, 67, 54, and 43 kDa are found in rat female reproductive organs
54000
HSL-immunoreactive bands at 84, 67, 54, and 43 kDa are found in rat female reproductive organs
67000
HSL-immunoreactive bands at 84, 67, 54, and 43 kDa are found in rat female reproductive organs
76000
predicted from cDNA; predicted from cDNA
82820
-
x * 82820, deduced from nucleotide sequence
84032
-
x * 84032, deduced from nucleotide sequence
84073
-
x * 84073, deduced from nucleotide sequence, HSL might be a homodimer in solution
85000
-
2 * 85000, immunoblotting, 40fold higher hydrolysis rate for cholesteryl ester than monomer
88000
-
x * 88000, SDS-PAGE
88200
-
x * 88200, SDS-PAGE, immunoblot
116000
-
x * 116000, SDS-PAGE, testis HSL
160000
-
sucrose density gradient centrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapor-diffusion method
purified recombinant wild-type and selenomethionine-labeled enzyme, mixing of 0.001 ml of protein solution and 0.001 ml of reservoir solution, method optimization, X-ray diffraction structure determination and analysis at 1.49 A resolution
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 10
-
stable for 24 h at 20C
706584
5.5 - 9
purified enzyme is broadly stable within a pH range of 5.5-9.0
690779
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 40
-
the entire enzyme recombinantly expressed as a fully soluble protein is more stable at 40C than its previously expressed recombinant counterpart, an insoluble form of the entire enzyme, cloned and expressed in Escherichia coli, and subsequently refolded to the active form
35 - 50
-
purified recombinant enzyme, pH 8.0, the enzyme activity is enhanced by 1-3 M trimethylamine N-oxide and betaine up to 5fold, overview. Denaturation temperature of the enzyme is 35.5C, in presence of 20% glycerol it increases to 43.5C, in presence of 20% glycerol and 1 M betaine to 44.5C, and in presence of 20% glycerol and 1 M trimethylamine N-oxide to 50.5C
49
-
melting temperature of the purified recombinant fully soluble full-length enzyme, irreversible inactivation. The thermally denatured HSL at 75C still contains a substantial amount of secondary structure
55
-
enzyme retains 70% of its activity after preincubation 1 h at 55C
additional information
-
proline does not activate and thermally stabilize the enzyme at 35-50C and concentrations of 1-3 M, but inhibits the enzyme activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stable to 4 cycles of freezing at -20C followed by thawing
-
the entire enzyme recombinantly expressed as a fully soluble protein is more stable than its previously expressed recombinant counterpart, an insoluble form of the entire enzyme, cloned and expressed in Escherichia coli, and subsequently refolded to the active form, circular dichroism
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 500 mM phosphate buffer, pH 7.0, 50% glycerol, 100 mM benzamidine, 1 mM dithiothreitol, 0.2% C13E12, 5 mg/ml leupeptin and 1 mg/ml pepstatin, at least 2 months, no loss of activity
-
4C, stable for 60 days
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion exchange chromatography followed by nickel affinity chromatography and dialysis
-
partially purified
-
partially purified, Q-Sepharose FF
-
pH 5.0, DE-52, hydroxyapatite
-
pH 5.0, DE-52, hydroxyapatite, Phenyl-Sepharose, Heparin-Sepharose
-
pH 5.0, DE-52, hydroxylapatite, Phenyl-Sepharose, heparin-Sepharose
-
pH 5.0, DE-52, Phenyl-Sepharose, Mono Q, Mono S
-
recombinant His-tagged enzyme by nickel affinity chromatography, gel filtration, and ultrafiltration
recombinant HSL
-
recombinant HSL, detergent-solubilization, Q-Sepharose, Phenyl-Sepharose
-
recombinant human HSL from baculovirus-infected insect cells
-
recombinant N- and C-terminally His6-tagged soluble full-length enzyme from Escherichia coli by nickel affinity chromatography and gel filtration
-
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned and expressed as a His-tagged fusion protein in Escherichia coli
-
cloning of cDNA
-
expressed in 293A cells; expressed in THP-1- cells
-
expressed in Escherichia coli; expressed in Escherichia coli
expression in CHO cells
-
expression in COS and insect cells
-
expression in Escherichia coli
expression in Sf9 insect cells and COS cells
-
expression of cDNA in COS cells
-
expression of HSL cDNA in HepG2 cells
-
expression of the entire enzyme, N-terminally and C-terminally His6-tagged, as a fully soluble protein in Escherichia coli in the presence of either the osmolyte trehalose, plus high salt concentration, or the membrane fluidizer benzyl alcohol. Addition of these compounds proves to be decisive in procuring a high expression level of stable, soluble, full-length recombinant protein
-
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
-
gene Est25, phylogenetic analysis, sequence comparisons, recombinant expression of His-tagged enzyme in Escherichia coli strain XL1-Blue
gene Lipe, encodes a specific HSL isoform including a 313 amino acid N-terminus encoded by the testis-specific exon T1
-
heart-specific HSL-overexpressing mice, transgenic (Tg) mice with heart-specific HSL overexpression are generated, and cardiac histology, function, lipid profile, and gene expressions are analyzed after induction of diabetes by streptozotocin. HSL overexpression inhibits cardiac steatosis in streptozotocin (STZ)-induced diabetic mice
-
human HSL is expressed from baculovirus-infected insect cells
-
isozyme HSL1, DNA and amino acid sequence determination and analysis, sequence comparison of HSL1 and HSL2, and phylogenetic analysis, quantitative real-time PCR expression analysis; isozyme HSL2, DNA and amino acid sequence determination and analysis, sequence comparison of HSL1 and HSL2, and phylogenetic analysis, quantitative real-time PCR expression analysis
E2JFF5, E2JFF6
overexpressed in BL21(DE3) cells
recombinant expression of His-tagged enzyme
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
4fold increase in activity with 4-nitrophenyl caproate, in contrast to wild-type mutant also shows activity against tributyrin. V158A mutant shows an improved thermostabilty compared with wild-type. V158A mutant shows a greater affinity to p-nitrophenyl acetate. Mutant is more sensitive to Cu2+, but less sensitive to Hg2+ compared to wild-type
-
activation of the protein kinase A pathway, by a cAMP analogue dibutyryl cyclic AMP, enhances expression of the enzyme and its phosphorylation at Ser660 and Ser563, but not at Ser565, concomitant with increased enzyme activity. An increase in enzyme is correlated with the liver X receptor target genes, steroid receptor element-binding protein 1c, and ATP binding cassette transporter A1
characterization of a 1.224 kb 5'-flanking region of ovine HSL: TATA-less promoter area, harboring several cis-regulatory elements. Strong promoter activities are unambiguously detected, using a -140/+18 nucleotide sequence
gene expression is notably enhanced in the adipose tissue during the fasting period, when lipolysis is highly increased in ruminant species; gene expression is notably enhanced in the adipose tissue during the fasting period, when lipolysis is highly increased in ruminant species
infection by live Mycobacterium leprae significantly suppresses the enzyme expression levels. This suppression is not observed with dead Mycobacterium leprae or latex bead controls
-
mutation shows no effect on substrate specificity. Mutant is less thermostable compared to wild-type. V158A mutant shows an improved thermostabilty compared with wild-type. W87F mutant shows a lower affinity to p-nitrophenyl acetate compared to wild-type. Mutant is more sensitive to Cu2+ and Hg2+ compared to wild-type
-
short term fasting over 4 weeks increases HSL1 and HSL2 mRNA expression in the adipose tissue, but only HSL1 mRNA levels increase in the liver and the red muscle. During a prolonged fast of 6 weeks, there is continued elevation of HSL1 and HSL2 mRNA levels in the liver and muscle, HSL mRNA expression in mesenteric fat declines, coincident with depletion of mesenteric fat mass. The upregulations are reversible; short term fasting over 4 weeks increases HSL1 and HSL2 mRNA expression in the adipose tissue, but only HSL1 mRNA levels increase in the liver and the red muscle. During a prolonged fast of 6 weeks, there is continued elevation of HSL1 and HSL2 mRNA levels in the liver and muscle, HSL mRNA expression in mesenteric fat declines, coincident with depletion of mesenteric fat mass. The upregulations are reversible
E2JFF5, E2JFF6
significantly increased activity with 4-nitrophenyl butyrate in the double mutant, double mutant shows similar affinity to p-nitrophenyl acetate
-
tumor necrosis factor-alpha suppresses the enzyme
-
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
HSL(-/-) mice
-
feeding with a high-cholesterol diet induces hepatic cholesteryl ester accumulation, show reduced activity of cholesteryl ester hydrolase, but not of TG lipase. Hepatocytes show reduced activity of cholesteryl ester hydrolase and contain more cholesteryl ester than those from HSL(+/+) mice even without the incubation with lipoproteins
Lep(ob/ob)/HSL(-/-)
-
mice lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) show massive accumulation of cholesteryl ester in the liver compared with Lep(ob/ob)/HSL(+/+) mice, while triacylglycerol accumulation was modest
DELTA644-658
-
reduced basal hydrolytic activity, no activation by cyclic AMP-dependent protein kinase
DELTA657-664
-
reduced basal hydrolytic activity, no activation by cyclic AMP-dependent protein kinase
DELTA666-683
-
very low basal and stimulated hydrolytic activity. Vmax with cholesteryl ester is 29fold lower than wild-type value. Vmax with p-nitrophenylbutyrate is 8fold lower than wild-type value
F650C
-
reduced activity against lipid-soluble but not water-soluble substrates
F654D
-
reduced activity against lipid-soluble but not water-soluble substrates
P651A
-
reduced activity against lipid-soluble but not water-soluble substrates
S423A
-
99% loss of cholesteryl oleate hydrolysis, more than 80% loss of trioleoylglycerol hydrolysis and more than 90% loss of dioleoylglycerol hydrolysis
S563A
-
98% loss of cholesteryl oleate hydrolysis, more than 80% loss of trioleoylglycerol hydrolysis and more than 90% loss of dioleoylglycerol hydrolysis
S563A/S565A
-
70% loss of cholesteryl oleate hydrolysis, 10% loss of trioleoylglycerol hydrolysis and 80% loss of dioleoylglycerol hydrolysis
S563D
-
approx. 20% increase in cholesteryl oleate hydrolysis compared to wild-type
S565A
-
70% loss of cholesteryl oleate hydrolysis, 35% loss of trioleoylglycerol hydrolysis and 30% loss of dioleoylglycerol hydrolysis
V158A
-
4fold increase in activity with 4-nitrophenyl caproate, in contrast to wild-type mutant also shows activity against tributyrin. V158A mutant shows an improved thermostabilty compared with wild-type. V158A mutant shows a greater affinity to p-nitrophenyl acetate. Mutant is more sensitive to Cu2+, but less sensitive to Hg2+ compared to wild-type
V158A/W87F
-
significantly increased activity with 4-nitrophenyl butyrate in the double mutant, double mutant shows similar affinity to p-nitrophenyl acetate
W87F
-
mutation shows no effect on substrate specificity. Mutant is less thermostable compared to wild-type. V158A mutant shows an improved thermostabilty compared with wild-type. W87F mutant shows a lower affinity to p-nitrophenyl acetate compared to wild-type. Mutant is more sensitive to Cu2+ and Hg2+ compared to wild-type
additional information
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
drug development
the requirement of dimerization for the function and stability of HSL-family enzymes focuses attention on the dimeric interface as a potential target for structure-aided drug design
medicine
synthesis