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Information on EC 3.1.1.79 - hormone-sensitive lipase and Organism(s) Rattus norvegicus and UniProt Accession P15304

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     3 Hydrolases
         3.1 Acting on ester bonds
             3.1.1 Carboxylic-ester hydrolases
                3.1.1.79 hormone-sensitive lipase
IUBMB Comments
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 , retinyl esters 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 . 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.
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Rattus norvegicus
UNIPROT: P15304
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
hormone-sensitive lipase, alpha/beta hydrolase, hsl protein, secreted lipase, est22, est25, mgmdl2, cardiac hsl, est06, mglip2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hormone-sensitive lipase
-
PATHWAY SOURCE
PATHWAYS
-
-
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
-
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
-
-
?
2-monooleoylglycerol + H2O
glycerol + oleate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl oleate + H2O
4-nitrophenol + oleate
show the reaction diagram
-
-
-
-
?
cholesterol oleate + H2O
cholesterol + oleate
show the reaction diagram
-
-
-
-
?
cholesteryl oleate + H2O
cholesterol + oleate
show the reaction diagram
cholesteryl oleate + H2O
cholesterol + oleic acid
show the reaction diagram
-
-
-
-
?
diacylglycerol + H2O
monoacylglycerol + a carboxylate
show the reaction diagram
-
-
-
-
?
dioleoylglycerol + H2O
monooleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
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
-
?
monoacylglycerol + H2O
glycerol + a carboxylate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl butyrate + H2O
p-nitrophenol + butanoate
show the reaction diagram
-
-
-
-
?
triacylglycerol + H2O
diacylglycerol + a carboxylate
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
dioleoylglycerol + oleate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
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 oleate + H2O
cholesterol + oleate
show the reaction diagram
-
-
-
-
?
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
-
-
-
-
?
trioleoylglycerol + H2O
1,2-dioleoylglycerol + oleate
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cis-cyclipostin R
-
-
diisopropyl fluorophosphate
diisopropylfluorophosphate
-
0.1 mM, 98% inhibition
methyl 2-(hexadecyloxy)-4-methyl-6,7-dihydro-1,3,2-dioxaphosphepine-5-carboxylate 2-oxide
-
-
NaF
-
0.1 mM, 90% inhibition
trans-cyclipostin P
-
irreversible
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
testosterone
-
left ventricle HSL activity against triglycerides is significantly elevated in intact rats supplemented with testosterone, testosterone replacement fully reverses this effect
additional information
-
activity in incubated soleus muscle increases in response to adrenaline
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.033
1,2-dioleoylglycerol
-
37°C
0.268 - 0.462
4-nitrophenyl oleate
0.0022 - 0.025
cholesteryl oleate
0.03
dioleoylglycerol
-
37°C, pH 7.0
0.0034
trioleoylglycerol
-
37°C, pH 7.0
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000004
trans-cyclipostin P
-
pH 7.4, 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000075
cis-cyclipostin R
Rattus norvegicus
-
pH 7.4, 37°C
0.00006
methyl 2-(hexadecyloxy)-4-methyl-6,7-dihydro-1,3,2-dioxaphosphepine-5-carboxylate 2-oxide
Rattus norvegicus
-
pH 7.4, 37°C
0.000025
trans-cyclipostin P
Rattus norvegicus
-
pH 7.4, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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
HSL is found in the epithelial cells nuclei
Manually annotated by BRENDA team
-
in virgin rats, immunoreactive hormone-sensitive lipase is observed in mammary adipocytes, diffuse staining is detected in epithelial cells. Positive staining for hormone-sensitive lipase is detected in the two types of cells in pregnant and lactating animals. As pregnancy advances, the staining intensity of immunoreactive hormone-sensitive lipase increases in the epithelial cells parallel to their proliferation, attaining the maximum during lactation. Both hormone-sensitive lipase protein and activity are lower in mammary glands from 20 and 21 day pregnant rats than from those of virgin rats. They return to virgin values on days 1 and 4 of lactation
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
LIPS_RAT
1068
0
116812
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
84000
HSL-immunoreactive bands at 84, 67, 54, and 43 kDa are found in rat female reproductive organs
160000
-
sucrose density gradient centrifugation
82820
-
x * 82820, deduced from nucleotide sequence
84000
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
additional information
-
substitution of S423 by several different amino acids completey abolishes lipase and esterase activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant HSL, detergent-solubilization, Q-Sepharose, Phenyl-Sepharose
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in CHO cells
-
expression in COS and insect cells
-
expression in Sf9 cells
-
expression in Sf9 insect cells and COS cells
-
expression of cDNA in COS cells
-
expression of HSL cDNA in HepG2 cells
-
expression Sf9 insect cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yeaman, S.J.
Hormone-sensitive lipase - new roles for an old enzyme
Biochem. J.
379
11-22
2004
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Langfort, J.; Ploug, T.; Ihlemann, J.; Enevoldsen, L.H.; Stallknecht, B.; Saldo, M.; Kjaer, M.; Holm, C.; Galbo, H.
Hormone-sensitive lipase (HSL) expression and regulation in skeletal muscle
Adv. Exp. Med. Biol.
441
219-228
1998
Rattus norvegicus
Manually annotated by BRENDA team
Holm, C.; Belfrage, P.; Fredrikson, G.
Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue
Biochem. Biophys. Res. Commun.
148
99-105
1987
Rattus norvegicus
Manually annotated by BRENDA team
Langfort, J.; Ploug, T.; Ihlemann, J.; Saldo, M.; Holm, C.; Galbo, H.
Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle
Biochem. J.
340
459-465
1999
Rattus norvegicus
-
Manually annotated by BRENDA team
Pease, R.J.; Wiggins, D.; Saggerson, E.D.; Tree, J.; Gibbons, G.F.
Metabolic characteristics of a human hepatoma cell line stably transfected with hormone-sensitive lipase
Biochem. J.
341
453-460
1999
Rattus norvegicus
-
Manually annotated by BRENDA team
Shen, W.J.; Patel, S.; Natu, V.; Kraemer, F.B.
Mutational analysis of structural features of rat hormone-sensitive lipase
Biochemistry
37
8973-8979
1998
Rattus norvegicus
Manually annotated by BRENDA team
Shen, W.J.; Patel, S.; Hong, R.; Kraemer, F.B.
Hormone-sensitive lipase functions as an oligomer
Biochemistry
39
2392-2398
2000
Rattus norvegicus
Manually annotated by BRENDA team
Holm, C.; Belfrage, P.; Fredrikson, G.
Human adipose tissue hormone-sensitive lipase: identification and comparison with other species
Biochim. Biophys. Acta
1006
193-197
1989
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Small, C.A.; Yeaman, S.J.; West, D.W.; Clegg, R.A.
Cholesterol ester hydrolysis and hormone-sensitive lipase in lactating rat mammary tissue
Biochim. Biophys. Acta
1082
251-254
1991
Rattus norvegicus
Manually annotated by BRENDA team
Osterlund, T.
Structure-function relationships of hormone-sensitive lipase
Eur. J. Biochem.
268
1899-1907
2001
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Holm, C.; Davis, R.C.; Fredrikson, G.; Belfrage, P.; Schotz, M.C.
Expression of biologically active hormone-sensitive lipase in mammalian (COS) cells
FEBS Lett.
285
139-144
1991
Rattus norvegicus
Manually annotated by BRENDA team
Fredrikson, G.; Belfrage, P.
Positional specificity of hormone-sensitive lipase from rat adipose tissue
J. Biol. Chem.
258
14253-14256
1983
Rattus norvegicus
Manually annotated by BRENDA team
Raclot, T.; Holm, C.; Langin, D.
Fatty acid specificity of hormone-sensitive lipase: implication in the selective hydrolysis of triacylglycerols
J. Lipid Res.
42
2049-2057
2001
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Awad, A.B.; Chattopadhyay, J.P.
Effect of dietary saturated fatty acids on intracellular free fatty acids and kinetic properties of hormone-sensitive lipase of rat adipocytes
J. Nutr.
116
1095-1100
1986
Rattus norvegicus
Manually annotated by BRENDA team
Holm, C.; Belfrage, P.; Osterlund, T.; Davis, R.C.; Schotz, M.C.; Langin, D.
Hormone-sensitive lipase: structure, function, evolution and overproduction in insect cells using the baculovirus expression system
Protein Eng.
7
537-541
1994
Rattus norvegicus
Manually annotated by BRENDA team
Wang, J.; Shen, W.J.; Patel, S.; Harada, K.; Kraemer, F.B.
Mutational analysis of the "regulatory module" of hormone-sensitive lipase
Biochemistry
44
1953-1959
2005
Rattus norvegicus
Manually annotated by BRENDA team
Lindvall, H.; Nevsten, P.; Stroem, K.; Wallenberg, R.; Sundler, F.; Langin, D.; Soerhede Winzell, M.; Holm, C.
A novel hormone-sensitive lipase isoform expressed in pancreatic beta-cells
J. Biol. Chem.
279
3828-3836
2004
Rattus norvegicus (Q6T861)
Manually annotated by BRENDA team
Martin-Hidalgo, A.; Huerta, L.; Alvarez, N.; Alegria, G.; Del Val Toledo, M.; Herrera, E.
Expression, activity, and localization of hormone-sensitive lipase in rat mammary gland during pregnancy and lactation
J. Lipid Res.
46
658-668
2005
Rattus norvegicus
Manually annotated by BRENDA team
Donsmark, M.; Langfort, J.; Holm, C.; Ploug, T.; Galbo, H.
Regulation and role of hormone-sensitive lipase in rat skeletal muscle
Proc. Nutr. Soc.
63
309-314
2004
Rattus norvegicus
Manually annotated by BRENDA team
Lobo, M.V.; Huerta, L.; Arenas, M.I.; Busto, R.; Lasuncion, M.A.; Martin-Hidalgo, A.
Hormone-sensitive lipase expression and IHC localization in the rat ovary, oviduct, and uterus
J. Histochem. Cytochem.
57
51-60
2009
Rattus norvegicus (P15304)
Manually annotated by BRENDA team
Langfort, J.; Jagsz, S.; Dobrzyn, P.; Brzezinska, Z.; Klapcinska, B.; Galbo, H.; Gorski, J.
Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle
Biochem. Biophys. Res. Commun.
399
670-676
2010
Rattus norvegicus
Manually annotated by BRENDA team
Ogasawara, J.; Nomura, S.; Rahman, N.; Sakurai, T.; Kizaki, T.; Izawa, T.; Ishida, H.; Haga, S.; Ohno, H.
Hormone-sensitive lipase is critical mediators of acute exercise-induced regulation of lipolysis in rat adipocytes
Biochem. Biophys. Res. Commun.
400
134-139
2010
Rattus norvegicus, Rattus norvegicus Wistar
Manually annotated by BRENDA team
Vasilieva, E.; Dutta, S.; Malla, R.K.; Martin, B.P.; Spilling, C.D.; Dupureur, C.M.
Rat hormone sensitive lipase inhibition by cyclipostins and their analogs
Bioorg. Med. Chem.
23
944-952
2015
Rattus norvegicus
Manually annotated by BRENDA team