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Information on EC 1.1.1.64 - testosterone 17beta-dehydrogenase (NADP+) and Organism(s) Rattus norvegicus and UniProt Accession O54939
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1.1.1.64 testosterone 17beta-dehydrogenase (NADP+)IUBMB Comments
Also oxidizes 3-hydroxyhexobarbital to 3-oxohexobarbital.
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Word Map
- 1.1.1.64
- androgen
- testis
- 17beta-hsd3
- androstenedione
- testicular
- leydig
- hsd17b3
-
steroidogenic
-
puberty
-
5alpha-reductase
- pseudohermaphroditism
-
genitalia
-
dehydrogenase-3
- estrone
- p450scc
- medicine
- drug development
- diagnostics
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
17betahsd3, 17beta-hydroxysteroid dehydrogenase 3, 17beta-hsd 3, testosterone 17beta-dehydrogenase (nadp+), 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
17-ketoreductase
-
-
-
-
NADP-dependent testosterone-17beta-oxidoreductase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
17beta-hydroxysteroid:NADP+ 17-oxidoreductase
Also oxidizes 3-hydroxyhexobarbital to 3-oxohexobarbital.
CAS REGISTRY NUMBER
COMMENTARY
9028-63-1
-
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
androstenedione + NADPH + H+
testosterone + NADP+
-
i.e. 4-androsten-17-ol-3-one
-
?
androstenedione + NADPH + H+
testosterone + NADP+
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1
i.e. 4-androsten-17beta-ol-3-one
-
?
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
androstenedione + NADPH + H+
testosterone + NADP+
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1
i.e. 4-androsten-17beta-ol-3-one
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3alpha,5alpha)-3-[(2,5-dimethyl-4-{[2-(trifluoromethyl)phenyl]sulfonyl}piperazin-1-yl)methyl]-3-hydroxyandrostan-17-one
the inhibitor RM-532-105 seems to have difficulties in penetrating inside the testis and is concentrated in the testicular capsule. Therefore it is unable to inhibit the 17bets-HSD3 located inside the testis. At a higher concentration, RM-532-105 significantly decreases the level of testosterone and dihydrotestosterone in rat plasma, in vivo effects of the inhibitor in testis and plasma, detailed overview
(3alpha,5alpha)-3-([(2R,5S)-2,5-dimethyl-4-[2-(trifluoromethyl)benzene-1-sulfonyl]piperazin-1-yl]methyl)-3-hydroxyandrostan-17-one
-
48.8-92.0% inhibition at 0.0001-0.001 mM
(3R,5'R,10S,13S)-4',5'-dibenzyl-10,13-dimethyltetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione
-
6.2-19.5% inhibition at 0.0001-0.001 mM
(3R,5'R,10S,13S)-5'-benzyl-10,13-dimethyltetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione
-
58.2-90.4% inhibition at 0.0001-0.001 mM
(3R,5'S,10S,13S)-4',5'-dibenzyl-10,13-dimethyltetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione
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25.6-87.3% inhibition at 0.0001-0.001 mM
(3R,5'S,10S,13S)-5'-benzyl-10,13-dimethyltetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione
-
18.5-63.2% inhibition at 0.0001-0.001 mM
(3S)-3,4-dibenzyl-1-oxa-4-azaspiro[5.5]undecan-2-one
-
47.3-92.1% inhibition at 0.0001-0.001 mM
(3S)-3-benzyl-1-oxa-4-azaspiro[5.5]undecan-2-one
-
24.2-24.3% inhibition at 0.0001-0.001 mM
5-[3,5-dichloro-4-(phosphonoxy)benzylidene]-3-(4-methoxyphenyl)-2-thioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3. When administered orally at a high dose of 100 mg/kg, compound shows approximately two times more potent testosterone-lowering effect against a positive control in the luteinizing hormone-releasing hormone-induced T production assay. The T-lowering effect continues at ca 10% level of control over 4 h after administration
bis(2-butoxyethyl) phthalate
-
potent inhibitor of testis 17beta-hydroxysteroid dehydrogenase type 3, additionally inhibits 3beta-hydroxysteriod dehydrogenase
dicyclohexyl phthalate
-
potent inhibitor of testis 17beta-hydroxysteroid dehydrogenase type 3, additionally inhibits 3beta-hydroxysteriod dehydrogenase
additional information
activity of 17beta-HSD is significantly decreased in metyrapone-induced corticosterone-deficient rat Leydig cells compared to control, whereas simultaneous administration of corticosterone partially prevented this and maintained the activity at near normal levels
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additional information
-
synthesis of 3-spiromorpholinone androsterone derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0285
bis(2-butoxyethyl) phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3 , pH 7.4, 37°C
0.05
bis(2-butoxyethyl) phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase , pH 7.4, 37°C
0.0085
dicyclohexyl phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3, pH 7.4, 37°C
0.0165
dicyclohexyl phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase, pH 7.4, 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000014
(3alpha,5alpha)-3-([(2R,5S)-2,5-dimethyl-4-[2-(trifluoromethyl)benzene-1-sulfonyl]piperazin-1-yl]methyl)-3-hydroxyandrostan-17-one
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000048
(3R,5'S,10S,13S)-4',5'-dibenzyl-10,13-dimethyltetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000022
(3R,5'S,10S,13S)-5'-benzyl-10,13-dimethyltetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2'-[1,4]oxazinane]-6',17(2H)-dione
Rattus norvegicus
-
pH and temperature not specified in the publication
0.0302
bis(2-butoxyethyl) phthalate
Rattus norvegicus
-
isoform 17beta-hydroxysteroid dehydrogenase type 3 , pH 7.4, 37°C
0.0825
bis(2-butoxyethyl) phthalate
Rattus norvegicus
-
isoform 3beta-hydroxysteriod dehydrogenase , pH 7.4, 37°C
0.0247
dicyclohexyl phthalate
Rattus norvegicus
-
isoform 3beta-hydroxysteriod dehydrogenase, pH 7.4, 37°C
0.09
dicyclohexyl phthalate
Rattus norvegicus
-
isoform 17beta-hydroxysteroid dehydrogenase type 3, pH 7.4, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the enzyme catalyzes the last step in the biosynthesis of the potent androgen testosterone (T), by stereoselectively reducing the C17 ketone of 4-androstene-3,17-dione (4-dione), with NADPH as cofactor
physiological function
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1
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). DHB3_RAT
306
0
34223
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Inano, H.; Tamaoki, B.
Testicular 17beta-hydroxysteroid dehydrogenas: molecular properties and reaction mechanism
Steroids
48
1-26
1986
Oryctolagus cuniculus, Ovis aries, Rattus norvegicus, Sus scrofa
Tamaoki, B-i.; Inano, H.
Testicular 17beta-hydroxysteroid dehydrogenase: its distribution, purification and properties
J. Steroid Biochem.
6
361-363
1975
Rattus norvegicus, Sus scrofa
Poirier, D.
Inhibitors of 17beta-hydroxysteroid dehydrogenases
Curr. Med. Chem.
10
453-477
2003
Canis lupus familiaris, Homo sapiens, Rattus norvegicus
Lota, R.K.; Dhanani, S.; Owen, C.P.; Ahmed, S.
Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a series of 4-hydroxyphenyl ketones as potential inhibitors of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3)
Bioorg. Med. Chem. Lett.
16
4519-4522
2006
Rattus norvegicus
Parthasarathy, C.; Balasubramanian, K.
Effects of corticosterone deficiency and its replacement on Leydig cell steroidogenesis
J. Cell. Biochem.
104
1671-1683
2008
Rattus norvegicus (O54939)
Hu, G.X.; Zhou, H.Y.; Li, X.W.; Chen, B.B.; Xiao, Y.C.; Lian, Q.Q.; Liang, G.; Kim, H.H.; Zheng, Z.Q.; Hardy, D.O.; Ge, R.S.
The (+)- and (-)-gossypols potently inhibit both 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 in human and rat testes
J. Steroid Biochem. Mol. Biol.
115
14-19
2009
Homo sapiens, Rattus norvegicus
Harada, K.; Kubo, H.; Abe, J.; Haneta, M.; Conception, A.; Inoue, S.; Okada, S.; Nishioka, K.
Discovery of potent and orally bioavailable 17beta-hydroxysteroid dehydrogenase type 3 inhibitors
Bioorg. Med. Chem.
20
3242-3254
2012
Rattus norvegicus, Homo sapiens (P37058)
Yuan, K.; Zhao, B.; Li, X.W.; Hu, G.X.; Su, Y.; Chu, Y.; Akingbemi, B.T.; Lian, Q.Q.; Ge, R.S.
Effects of phthalates on 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 activities in human and rat testes
Chem. Biol. Interact.
195
180-188
2012
Rattus norvegicus, Homo sapiens (P37058)
Latif, S.A.; Shen, M.; Ge, R.S.; Sottas, C.M.; Hardy, M.P.; Morris, D.J.
Role of 11beta-OH-C(19) and C(21) steroids in the coupling of 11beta-HSD1 and 17beta-HSD3 in regulation of testosterone biosynthesis in rat Leydig cells
Steroids
76
682-689
2011
Rattus norvegicus (O54939)
Djigoue, G.B.; Kenmogne, L.C.; Roy, J.; Poirier, D.
Synthesis of 3-spiromorpholinone androsterone derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3
Bioorg. Med. Chem. Lett.
23
6360-6362
2013
Rattus norvegicus
Roy, J.; Fournier, M.A.; Maltais, R.; Kenmogne, L.C.; Poirier, D.
Reprint of in vitro and in vivo evaluation of a 3beta-androsterone derivative as inhibitor of 17beta-hydroxysteroid dehydrogenase type 3
J. Steroid Biochem. Mol. Biol.
153
170-178
2015
Homo sapiens (P37058), Rattus norvegicus (O54939), Rattus norvegicus Sprague-Dawley (O54939)
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