Information on EC 1.14.14.14 - aromatase

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY
1.14.14.14
-
RECOMMENDED NAME
GeneOntology No.
aromatase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
19-hydroxyandrost-4-ene-3,17-dione + O2 + a reduced flavoprotein = 19-oxo-androst-4-ene-3,17-dione + 2 H2O + an oxidized flavoprotein
show the reaction diagram
(2b)
-
-
-
19-hydroxytestosterone + O2 + a reduced flavoprotein = 19-oxotestosterone + 2 H2O + an oxidized flavoprotein
show the reaction diagram
(1b)
-
-
-
19-oxoandrost-4-ene-3,17-dione + O2 + a reduced flavoprotein = estrone + formate + H2O + an oxidized flavoprotein
show the reaction diagram
catalytic reaction mechanism, detailed overview
-
-
-
19-oxotestosterone + O2 + a reduced flavoprotein = 17beta-estradiol + formate + H2O + an oxidized flavoprotein
show the reaction diagram
(1c)
-
-
-
androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins = estrone + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
(2)
-
-
-
androst-4-ene-3,17-dione + O2 + a reduced flavoprotein = 19-hydroxyandrost-4-ene-3,17-dione + H2O + an oxidized flavoprotein
show the reaction diagram
(2a)
-
-
-
testosterone + 3 O2 + 3 reduced flavoproteins = 17beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
(1)
-
-
-
testosterone + O2 + a reduced flavoprotein = 19-hydroxytestosterone + H2O + an oxidized flavoprotein
show the reaction diagram
(1a)
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Steroid hormone biosynthesis
-
-
Metabolic pathways
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-
SYSTEMATIC NAME
IUBMB Comments
testosterone monooxygenase (17beta-estradiol-forming)
A cytochrome P-450. The enzyme catalyses three sequential hydroxylations of the androgens androst-4-ene-3,17-dione and testosterone, resulting in their aromatization and forming the estrogens estrone and 17beta-estradiol, respectively.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CYP19A1
-
-
gene name
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Homo sapiens ATCC HTB-144
-
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
16alpha-hydroxytestosterone + 3 O2 + 3 reduced flavoproteins
16alpha,17beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
19-hydroxyandrost-4-ene-3,17-dione + O2 + a reduced flavoprotein
19-oxo-androst-4-ene-3,17-dione + 2 H2O + an oxidized flavoprotein
show the reaction diagram
-
-
-
?
19-oxoandrost-4-ene-3,17-dione + O2 + a reduced flavoprotein
estrone + formate + H2O + an oxidized flavoprotein
show the reaction diagram
-
-
-
?
androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins
estrone + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
-
overall reaction
?
androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins
estrone + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins
estrone + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
testosterone + 3 O2 + 3 reduced flavoproteins
17beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
testosterone + 3 O2 + 3 reduced flavoproteins
17beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
androst-4-ene-3,17-dione + O2 + a reduced flavoprotein
19-hydroxyandrost-4-ene-3,17-dione + H2O + an oxidized flavoprotein
show the reaction diagram
-
-
-
?
additional information
?
-
-
19-oxygenated androgen intermediates are biosynthesized sequentially in a step-wise fashion as the cytochrome P450 and NADPH-cytochrome P450 reductase form transient complexes, and the amount of isolatable 19-oxygenated androgen is proportional to the amount of excess cytochrome P450 component
-
-
-
additional information
?
-
-
the aromatization of androstenedione probably involves two successive hydroxylations at the C-19 methyl group, mediated by a common catalytic site with the third and rate-determining 2beta-hydroxylation taking place at a different enzyme site
-
-
-
additional information
?
-
-
the rate of entry of the first electron into the oxidized P450 substrate complex may be rate limiting in the aromatization of C19 but not C18 steroids
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins
estrone + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
androst-4-ene-3,17-dione + 3 O2 + 3 reduced flavoproteins
estrone + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
testosterone + 3 O2 + 3 reduced flavoproteins
17beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
testosterone + 3 O2 + 3 reduced flavoproteins
17beta-estradiol + formate + 4 H2O + 3 oxidized flavoproteins
show the reaction diagram
-
overall reaction
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cytochrome P450
-
may be regulated by phosphorylation
-
cytochrome P450
-
inhibitors 7,8-benzoflavone and chrysin induce spectral changes in the aromatase cytochrome P450
-
cytochrome P450
-
specific content of 11.5 nmol of P450/mg of protein. Enzyme displays spectroscopic properties typical of the ferric and ferrous forms of cytochrome P-450
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
19-hydroxyandrost-4-ene-3,17-dione
-
competitive with substrates androst-4-ene-3,17-dione and 19-oxoandrost-4-ene-3,17-dione
19-hydroxyandrost-4-ene-3,17-dione
-
competitively inhibits the formation of 19-hydroxyandrost-4-ene-3,17-dione and estrogen
19-nortestosterone
-
competitive inhibitor of both aromatization and cytochrome P450 binding of androst-4-ene-3,17-dione
19-oxoandrost-4-ene-3,17-dione
-
competitive with substrates androst-4-ene-3,17-dione and 19-hydroxyandrost-4-ene-3,17-dione
19-oxoandrost-4-ene-3,17-dione
-
competitively inhibits the formation of 19-oxoandrost-4-ene-3,17-dione and estrogen
7,8-Benzoflavone
-
competitive inhibitor, induces spectral changes in the aromatase cytochrome P450
8-prenylnaringenin
-
flavonoid isolated from hop, inhibits enzyme activity, no effect on enzyme expression
Aminoglutethimide
-
0.005 mM, 54% residual activity
androst-4-ene-3,17-dione
-
competitive inhibitor of both aromatization and cytochrome P450 binding of 19-nortestosterone
apigenin
-
-
chrysin
-
competitive inhibitor, induces spectral changes in the aromatase cytochrome P450
diethylaminoethyl-2,2-diphenylvalerate
-
0.05 mM, 64% residual activity
-
flavanone
-
-
flavone
-
-
isoxanthohumol
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flavonoid isolated from hop, inhibits enzyme activity, no effect on enzyme expression
-
quercetin
-
-
xanthohumol
-
flavonoid isolated from hop, inhibits enzyme activity, no effect on enzyme expression
KCN
-
5 mM, 80% residual activity
additional information
-
treatment with alkaline phosphatase results in loss of activity, as well as incubation in phosphate-free buffer
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additional information
-
not inhibitory: 5,6-benzoflavone
-
additional information
-
lager beer, alcohol-free beer, stout beer, and xanthohumol-rich stout beer significantly decrease aromatase activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.058
16alpha-hydroxytestosterone
-
pH 7.2, 37C
0.00006
androst-4-ene-3,17-dione
-
pH 7.2, 37C
0.00021
testosterone
-
pH 7.2, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00038
19-hydroxyandrost-4-ene-3,17-dione
-
substrate 19-oxoandrost-4-ene-3,17-dione, pH 7.0, 37C
0.00045
19-hydroxyandrost-4-ene-3,17-dione
-
substrate androst-4-ene-3,17-dione, pH 7.0, 37C
0.0015
19-oxoandrost-4-ene-3,17-dione
-
substrate 19-hydroxyandrost-4-ene-3,17-dione, pH 7.0, 37C
0.003
19-oxoandrost-4-ene-3,17-dione
-
substrate androst-4-ene-3,17-dione, pH 7.0, 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00006
7,8-Benzoflavone
Homo sapiens
-
substrate testosterone, pH 7.2, 37C
0.00007
7,8-Benzoflavone
Homo sapiens
-
substrate androst-4-ene-3,17-dione, pH 7.2, 37C
0.000065
8-prenylnaringenin
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.001
apigenin
Homo sapiens
-
substrate testosterone, pH 7.2, 37C
0.0012
apigenin
Homo sapiens
-
substrate androst-4-ene-3,17-dione, pH 7.2, 37C
0.0004
chrysin
Homo sapiens
-
substrate testosterone, pH 7.2, 37C
0.0005
chrysin
Homo sapiens
-
substrate androst-4-ene-3,17-dione, pH 7.2, 37C
0.005
flavanone
Homo sapiens
-
substrate testosterone, pH 7.2, 37C
0.008
flavanone
Homo sapiens
-
substrate androst-4-ene-3,17-dione, pH 7.2, 37C
0.005
flavone
Homo sapiens
-
substrate testosterone, pH 7.2, 37C
0.008
flavone
Homo sapiens
-
substrate androst-4-ene-3,17-dione, pH 7.2, 37C
0.081
isoxanthohumol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
-
0.01
quercetin
Homo sapiens
-
substrate testosterone, pH 7.2, 37C
0.012
quercetin
Homo sapiens
-
substrate androst-4-ene-3,17-dione, pH 7.2, 37C
0.0203
xanthohumol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
57
-
pH 7.2, 37C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
cell line expresses aromatase mRNA and shows a cytoplasmic pattern of aromatase immunoreactivity. In addition, the cell line expresses estrogen receptor alpha
Manually annotated by BRENDA team
-
trophoblastic tumor cell of placenta
Manually annotated by BRENDA team
Homo sapiens ATCC HTB-144
-
trophoblastic tumor cell of placenta
-
Manually annotated by BRENDA team
-
increases in aromatase activities of the ovary and testis precede the onset of the ovarian and testicular development. Aromatase activities reach the highest level at the growing stage in February and the mature stage in March, and show a striking decrease at the spawning stage in April. Contents of ovarian and testicular estradiol-17beta change similarly to the profile of aromatase activities in the ovary and testis, although estrone shows no change
Manually annotated by BRENDA team
-
cell line expresses aromatase mRNA and shows a cytoplasmic pattern of aromatase immunoreactivity. In addition, the cell line expresses estrogen receptor alpha
Manually annotated by BRENDA team
-
immunoreactivities against aromatase and estradiol-17beta are detected in the cells along the inside of the acinar wall of the testis
Manually annotated by BRENDA team
-
cell line expresses aromatase mRNA and shows a cytoplasmic pattern of aromatase immunoreactivity. In addition, the cell line expresses estrogen receptor alpha
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 55000, SDS-PAGE
multimer
-
enzyme is composed of cytochrome P450 and NADPH-cytochrome P450 reductase components
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
treatment with alkaline phosphatase results in loss of activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
to 1.8 A resolution, in complex with its natural substrate androst-4-ene-3,17-dione. Aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues complement the steroid backbone
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
from microsome. Full enzymatic activity can be reconstituted with rabbit liver microsomal cytochrome P-450 reductase and Nonidet P-40
-