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Information on EC 1.1.1.B40 - 11beta-hydroxysteroid dehydrogenase (NAD+) and Organism(s) Rattus norvegicus and UniProt Accession P16232
for references in articles please use BRENDA:EC1.1.1.B40preliminary BRENDA-supplied EC number
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1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+)Specify your search results
Word Map
- 1.1.1.B40
- glucocorticoid
-
mineralocorticoid
- cortisone
- aldosterone
- hypertension
- adrenal
- 11-dehydrocorticosterone
- dexamethasone
- urinary
- fetal
- carbenoxolone
-
glycyrrhetinic
- 11beta-hsds
-
beta-hsd1
- nadp
- acth
- renin
- hypokalemia
- spironolactone
- tetrahydrocortisol
-
cortisol-cortisone
-
liquorice
- thf
-
adrenalectomized
-
cushing
-
11-keto
-
beta-reductase
-
glycyrrhizic
-
hypopituitary
- medicine
-
3hcorticosterone
-
prereceptor
- pharmacology
-
11-beta-hydroxysteroid
-
feto-placental
-
low-renin
- drug development
-
11-dehydro
-
oxo-reductase
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
11 beta-hydroxysteroid dehydrogenase, 11 beta-hydroxysteroid dehydrogenase type 2, 11beta-hsd type 2, 11beta-ohsd, 11beta-hsd 2, 11-beta hydroxysteroid dehydrogenase type 2, type 2 11beta-hydroxysteroid dehydrogenase, 11beta hydroxysteroid dehydrogenase type 2, 11beta-hydroxysteroid dehydrogenase type-2, nad(+)-dependent 11beta-dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
11beta-hydroxysteroid dehydrogenase type 2
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
an 11beta-hydroxysteroid + NAD+ = an 11-oxosteroid + NADH + H+
the three-dimensional organization of the hydrophobic substrate binding pocket is responsible for species-specific variability of activity with different substrates, overview
-
SYSTEMATIC NAME
IUBMB Comments
11beta-hydroxysteroid:NAD+ 11-oxidoreductase
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
11-dehydrocorticosterone + beta-NADPH
corticosterone + beta-NADP+
-
higher activity
-
-
r
11-dehydrocorticosterone + NADPH
corticosterone + NADP+
-
isozyme 11beta-HSD1
-
-
?
11beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
1beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
-
i.e. corticosterone, no reductase activity in aldosterone-sensitive collecting duct
-
-
ir
7-oxocholesterol + NADPH + H+
7beta-hydroxycholesterol + NADP+
-
isozyme 11beta-HSD1, stereospecific reaction
-
-
?
11beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
-
i.e. corticosterone
-
-
?
11beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
-
i.e. corticosterone, no enzyme activity in reverse reaction direction
-
-
ir
corticosterone + NAD+
11-dehydrocorticosterone + NADH + H+
-
-
-
-
?
corticosterone + NAD+
11-dehydrocorticosterone + NADH + H+
-
-
-
-
ir
cortisol + NAD+
cortisone + NADH
-
isozyme 11beta-HSD2 catalyzes the reverse reaction with cofactor NAD+
-
-
ir
cortisol + NAD+
cortisone + NADH
-
isozyme 11beta-HSD2 highly prefers the oxidation of cortisol
-
-
r
cortisol + NAD+
cortisone + NADH
-
isozyme 11beta-HSD2 is involved in inactivation of glucocorticoids, forskolin is involved in regulation of isozyme 11beta-HSD2 via intracellular cAMP
-
-
ir
cortisone + NADPH + H+
cortisol + NADP+
-
isozyme 11beta-HSD1, activation
-
-
?
additional information
?
-
-
effects of hypertension on cardiac steroid metabolism, overview
-
-
?
additional information
?
-
-
estradiol has a regulatory function on the isozymes in the liver, isozyme 11beta-HSD1 expression is about 30% reduced in castrated male rats, while expression of isozyme 11beta-HSD2 is increased, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
11-dehydrocorticosterone + NADPH
corticosterone + NADP+
-
isozyme 11beta-HSD1
-
-
?
11beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
1beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
-
i.e. corticosterone, no reductase activity in aldosterone-sensitive collecting duct
-
-
ir
cortisone + NADPH + H+
cortisol + NADP+
-
isozyme 11beta-HSD1, activation
-
-
?
11beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
-
i.e. corticosterone
-
-
?
11beta,21-dihydroxypregn-4-en-3,20-dione + NAD+
21-hydroxy-pregn-4-en-3,11,20-trione + NADH
-
i.e. corticosterone, no enzyme activity in reverse reaction direction
-
-
ir
corticosterone + NAD+
11-dehydrocorticosterone + NADH + H+
-
-
-
-
?
corticosterone + NAD+
11-dehydrocorticosterone + NADH + H+
-
-
-
-
ir
cortisol + NAD+
cortisone + NADH
-
isozyme 11beta-HSD2 highly prefers the oxidation of cortisol
-
-
r
cortisol + NAD+
cortisone + NADH
-
isozyme 11beta-HSD2 is involved in inactivation of glucocorticoids, forskolin is involved in regulation of isozyme 11beta-HSD2 via intracellular cAMP
-
-
ir
additional information
?
-
-
effects of hypertension on cardiac steroid metabolism, overview
-
-
?
additional information
?
-
-
estradiol has a regulatory function on the isozymes in the liver, isozyme 11beta-HSD1 expression is about 30% reduced in castrated male rats, while expression of isozyme 11beta-HSD2 is increased, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3beta)-3-hydroxyandrost-5-en-17-one
-
treatment of rats induces a shift from isoform 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids. Dehydroepiandrosterone likely modulates the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing CCAAT/enhancer-binding protein beta mRNA and protein expression
3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic-acid
-
i.e. glycyrrhetinic acid; more effective for 11-dehydrogenase than for 11-oxoreductase activity
estradiol
-
50% inhibition, DTT protects at 10 mM, estradiol has a regulatory function on the isozymes in the liver
mono (2-ethylhexyl) phthalate
-
competitive inhibitor of 11beta-HSD2, possibly via competing with the cofactor NAD+
additional information
-
inhibitory effects in intact cells and IC50 values, overview, structure-based pharmacophore models for isozyme 11beta-HSD1 inhibitors using crystal structure 1XU7, 1XU9, and 2 BEL
-
additional information
-
isozyme 11beta-HSD1 expression is about 30% reduced in castrated male rats, while expression of isozyme 11beta-HSD2 is increased, overview
-
additional information
-
isozyme 11beta-HSD2 expression is highly reduced in proliferating cells
-
additional information
-
not inhibited by dimethyl phthalate, butylbenzyl phthalate, di(2-ethylhexyl) phthalate, di-n-heptyl phthalate, diisononyl phthalate, and diisodecyl phthalate
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00085
11-Dehydrocorticosterone
-
pH 7.4, 37°C, recombinant isozyme 11beta-HSD1
0.00108
11beta,21-dihydroxypregn-4-en-3,20-dione
-
temperature not specified in the publication, pH 9
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
2'-hydroxyflavanone
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
0.0021
abietic acid
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
0.00035
carbenoxolone
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
0.00055
chenodeoxycholic acid
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
0.054
flavanone
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
0.00044
glycyrrhetinic acid
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
0.00043
T0504
-
pH 7.4, 37°C, isozyme 11beta-HSD1, inhibition of cortisol oxidation
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00088
(+/-)-gossypol
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00005
carbenoxolone
Rattus norvegicus
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
isozyme expression, and isozyme and cofactor specific activities in kidney microsomes, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
11HSD1 is highly expressed in various brain structures, including the hippocampus
-
high-fat fed animals overexpress 11beta-hydroxysteroid dehydrogenase type 2 in subcutaneous but not in retroperitoneal fat. Enzyme mRNA levels strongly correlate in both tissues with different parameters related to obesity, such as body weight, adiposity, and insulin resistance
-
11beta-HSD2 in the adult brain is thought to protect mineralocorticoid receptors from inactivation by corticosterone
-
isoform 11beta-HSD1 is clearly expressed while isoform 11beta-HSD2 is much less prominent, 11beta-HSD1 protein expression predominates in endothelial cells and varies during periods of growth
-
of normotensive and hypertensive rats, the latter are hyperthrophied and fibrotic and have structural alterations in the coronary circulation, expression of isozymes 11beta-HSD1 and 11beta-HSD2, overview
-
mainly isozyme 11beta-HSD2, the concentration of isozyme 11beta-HSD1 is 10-100fold lower, expression analysis, isozyme 11beta-HSD2 shows strong expression and activity in quiescent cells
additional information
-
11betaHSD2 mRNA and protein expression increases significantly after treatment with estradiol; renal 11beta-HSD1 mRNA and protein expression decrease to very low levels after estradiol treatment
additional information
-
isozyme 11beta-HSD1 expression is about 30% reduced in castrated male rats, while expression of isozyme 11beta-HSD2 is increased, overview
additional information
-
isozyme 11beta-HSD2 expression is highly reduced in proliferating cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) is an enzyme that regulates the conversion of glucocorticoids from inactive to active form. Expression of expression of glucocorticoid and mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenase type 1 determines the sensitivity of the hippocampus to glucocorticoids, which mediate the feedbac inhibition of the hypothalamus-pituitary-adrenal axis during stress response via the hippocampus. Depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas independent of strain, stress inhibits the glucorticoid receptor in the dorsal hippocampus, which is predominantly involved in cognitive functions. F344 rats may amplify the hippocampal glucocorticoid signal more effectively than the stressed Wistar and Lewis rats, or the positive effect of stressful stimuli on 11HSD1 requires a longer stress exposure in the Wistar and Lewis Rattus strains
physiological function
-
the placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) shields the fetus from maternal glucocorticoid excess by catalyzing the conversion of these hormones into biologically inactive derivatives
additional information
-
species-specific differences of rat and human placental 11beta-HSD2 steroid turnover, species-specific expression of corticotropin-releasing hormone and steroids in human and rat term placenta
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DHI1_RAT
288
0
31883
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene 11HSD1, genotyping, quantitative isozyme expression analysis in brain of different strains
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
11HSD1 expression is increased by stress in the hippocampus, i.e. in the limbic structure that is activated by stress, effect of stress on the expression of 11HSD1 in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulates 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
treatment of rats with dehydroepiandrosterone induces a shift from isoform 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids
medicine
-
high-fat fed animals overexpress 11beta-hydroxysteroid dehydrogenase type 2 in subcutaneous but not in retroperitoneal fat. Enzyme mRNA levels strongly correlate in both tissues with different parameters related to obesity, such as body weight, adiposity, and insulin resistance
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Alfaidy, N.; Blot-Chabaud, M.; Robic, D.; Kenouch, S.; Bourbouze, R.; Bonvalet, J.P.; Farman, N.
Characteristics and regulation of 11beta-hydroxysteroid dehydrogenase of proximal and distal nephron
Biochim. Biophys. Acta
1243
461-468
1995
Rattus norvegicus
Monder, C.
The forms and functions of 11beta-hydroxysteroid dehydrogenase
J. Steroid Biochem. Mol. Biol.
45
161-165
1993
Rattus norvegicus
Hundertmark, S.; Ragosch, V.; Schein, B.; Buhler, H.; Fromm, M.; Lorenz, U.; Weitzel, H.K.
11-beta-Hydroxysteroid dehydrogenase of rat lung: Enzyme kinetic, oxidase-reductase ration, electrolyte and trace element dependence
Enzyme Protein
47
83-91
1993
Rattus norvegicus
Gomez-Sanchez, E.P.; Ganjam, V.; Chen, Y.J.; Liu, Y.; Zhou, M.Y.; Toroslu, C.; Romero, D.G.; Hughson, M.D.; de Rodriguez, A.; Gomez-Sanchez, C.E.
Regulation of 11beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol
Am. J. Physiol.
285
E272-279
2003
Rattus norvegicus
Holmes, M.C.; Yau, J.L.W.; Kotelevtsev, Y.; Mullins, J.J.; Seckl, J.R.
11beta-Hydroxysteroid dehydrogenases in the brain: two enzymes two roles
Ann. N. Y. Acad. Sci.
1007
357-366
2003
Mus musculus, Rattus norvegicus
Waddell, B.J.; Hisheh, S.; Krozowski, Z.S.; Burton, P.J.
Localization of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the male reproductive tract
Endocrinology
144
3101-3106
2003
Rattus norvegicus
Zallocchi, M.L.; Matkovic, L.; Calvo, J.C.; Damasco, M.C.
Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2
J. Cell. Biochem.
92
591-602
2004
Rattus norvegicus
Burton, P.J.; Waddell, B.J.
Myometrial expression of 11beta-hydroxysteroid dehydrogenase type 2 in rat pregnancy
J. Endocrinol.
172
519-526
2002
Rattus norvegicus
Gomez-Sanchez, E.P.; Venkataseshu, G.; Chen, Y.J.; Liu, Y.; Zhou, M.Y.; Toroslu, C.; Romero, D.G.; Hughson, M.D.; de Rodriguez, A.; Gomez-Sanchez, C.E.
Regulation of 11beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol
Am. J. Physiol. Endocrinol. Metab.
285
E272-E279
2003
Rattus norvegicus
Groyer, G.; Eychenne, B.; Girard, C.; Rajkowski, K.; Schumacher, M.; Cadepond, F.
Expression and functional state of the corticosteroid receptors and 11 beta-hydroxysteroid dehydrogenase type 2 in Schwann cells
Endocrinology
147
4339-4350
2006
Rattus norvegicus
Arampatzis, S.; Kadereit, B.; Schuster, D.; Balazs, Z.; Schweizer, R.A.; Frey, F.J.; Langer, T.; Odermatt, A.
Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six species
J. Mol. Endocrinol.
35
89-101
2005
Canis lupus familiaris, Cavia porcellus (Q6QLL4), Homo sapiens (P28845), Homo sapiens (P80365), Mesocricetus auratus (Q6R0J2), Mus musculus, Rattus norvegicus
Mazancova, K.; Kopecky, M.; Miksik, I.; Pacha, J.
11beta-Hydroxysteroid dehydrogenase in the heart of normotensive and hypertensive rats
J. Steroid Biochem. Mol. Biol.
94
273-277
2005
Rattus norvegicus
Balazs, Z.; Schweizer, R.A.; Frey, F.J.; Rohner-Jeanrenaud, F.; Odermatt, A.
DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding proteins
J. Am. Soc. Nephrol.
19
92-101
2008
Rattus norvegicus
Milagro, F.I.; Campion, J.; Martinez, J.A.
11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity
J. Steroid Biochem. Mol. Biol.
104
81-84
2007
Rattus norvegicus
Zhao, B.; Chu, Y.; Huang, Y.; Hardy, D.O.; Lin, S.; Ge, R.S.
Structure-dependent inhibition of human and rat 11beta-hydroxysteroid dehydrogenase 2 activities by phthalates
Chem. Biol. Interact.
183
79-84
2010
Homo sapiens, Rattus norvegicus
Chen, B.B.; Lin, H.; Hu, G.X.; Su, Y.; Zhou, H.Y.; Lian, Q.Q.; Cai, H.; Hardy, D.O.; Gu, D.Y.; Ge, R.S.
The (+)- and (-)-gossypols potently inhibit human and rat 11beta-hydroxysteroid dehydrogenase type 2
J. Steroid Biochem. Mol. Biol.
113
177-181
2009
Homo sapiens, Rattus norvegicus
Gong, R.; Morris, D.J.; Brem, A.S.
Variable expression of 11beta Hydroxysteroid dehydrogenase (11beta-HSD) isoforms in vascular endothelial cells
Steroids
73
1187-1196
2008
Bos taurus, Homo sapiens, Rattus norvegicus
Zhao, B.; Lian, Q.; Chu, Y.; Hardy, D.O.; Li, X.K.; Ge, R.S.
The inhibition of human and rat 11beta-hydroxysteroid dehydrogenase 2 by perfluoroalkylated substances
J. Steroid Biochem. Mol. Biol.
125
143-147
2011
Rattus norvegicus, Homo sapiens (P80365)
Ergang, P.; Kuzelova, A.; Sotak, M.; Klusonova, P.; Makal, J.; Pacha, J.
Distinct effect of stress on 11beta-hydroxysteroid dehydrogenase type 1 and corticosteroid receptors in dorsal and ventral hippocampus
Physiol. Res.
63
255-261
2014
Rattus norvegicus (P16232)
Heussner, K.; Ruebner, M.; Huebner, H.; Rascher, W.; Menendez-Castro, C.; Hartner, A.; Fahlbusch, F.B.; Rauh, M.
Species differences of 11beta-hydroxysteroid dehydrogenase type 2 function in human and rat term placenta determined via LC-MS/MS
Placenta
37
79-84
2016
Homo sapiens (P80365), Rattus norvegicus, Rattus norvegicus Wistar
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