Information on EC 2.1.1.6 - catechol O-methyltransferase

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

EC NUMBER
COMMENTARY
2.1.1.6
-
RECOMMENDED NAME
GeneOntology No.
catechol O-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
show the reaction diagram
mechanism
-
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
show the reaction diagram
mechanism
-
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
show the reaction diagram
ordered reaction mechanism with S-adenosyl-L-methionine as the leading substrate
-
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
show the reaction diagram
ordered reaction mechanism with S-adenosyl-L-methionine as the leading substrate
-
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
show the reaction diagram
study on mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
O-methylation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3,5-dimethoxytoluene biosynthesis
-
-
Betalain biosynthesis
-
-
betaxanthin biosynthesis
-
-
dopamine degradation
-
-
L-dopa degradation
-
-
Metabolic pathways
-
-
noradrenaline and adrenaline degradation
-
-
Steroid hormone biosynthesis
-
-
Tyrosine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:catechol O-methyltransferase
The mammalian enzyme acts more rapidly on catecholamines such as adrenaline or noradrenaline than on catechols.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
catechol methyltransferase
-
-
-
-
catechol-O-methyl transferase
-
-
catechol-O-methyl transferase
-
-
catechol-O-methyl transferase, membrane bound
-
-
catechol-O-methyl transferase, soluble
-
-
catechol-O-methyltransferase
-
-
catechol-O-methyltransferase
-
-
catechol-O-methyltransferase
-
soluble and membrane-bound isoforms encoded by a single gene
catechol-O-methyltransferase
-
-
catechol-O-methyltransferase
-
-
catechol-O-methyltransferase
-
-
catechol-O-transferase
-
-
catecholamine O-methyltransferase
-
-
-
-
COMT
A3F6Y9
-
COMT
P21964
-
COMT
P22734
-
COMT
-
-
COMT I
-
-
-
-
COMT II
-
-
-
-
COMT-mb
-
catechol-O-methyltransferase, membrane-bound isoform
COMT-s
-
catechol-O-methyltransferase, soluble isoform
COMT1
-
isoform
COMT2
-
isoform
L-COMT
-
large variant of catechol O-methyltransferase
MB-COMT
-
membrane-bound COMT
MB-COMT
-
-
MB-COMT
-
membrane-bound enzyme form
MB-COMT
-
membrane-bound form of catechol-O-methyltransferase
MB-COMT
-
membrane-bound isoform
MB-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
MB-COMT
-
membrane-bound catechol-O-methyltransferase
MB-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
MB-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
MB-COMT
-
membrane-bound form of catechol-O-methyltransferase
MB-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
methyltransferase, catechol
-
-
-
-
S-COMT
-
soluble COMT
S-COMT
-
-
S-COMT
-
soluble enzyme form
S-COMT
-
soluble form of catechol-O-methyltransferase
S-COMT
-
soluble isoform
S-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
S-COMT
P21964
-
S-COMT
-
soluble catechol-O-methyltransferase
S-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
S-COMT
-
small variant of catechol O-methyltransferase
S-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
S-COMT
P22734
-
S-COMT
P22734
soluble COMT
S-COMT
-
soluble form of catechol-O-methyltransferase
S-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
SCOMT
-
-
SCOMT
-
soluble isoform
CAS REGISTRY NUMBER
COMMENTARY
9012-25-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
common marmoset
-
-
Manually annotated by BRENDA team
African catfish
-
-
Manually annotated by BRENDA team
CHO cell line
-
-
Manually annotated by BRENDA team
2 forms
-
-
Manually annotated by BRENDA team
2 forms which differ in nature of intramolecular disulfide bonds
-
-
Manually annotated by BRENDA team
a common single-nucleotide polymorphism within COMT, Val158Met, significantly affects protein abundance and enzyme activity but not mRNA expression levels. Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function
-
-
Manually annotated by BRENDA team
both S-COMT and MB-COMT
-
-
Manually annotated by BRENDA team
hepatoma cell line G2
-
-
Manually annotated by BRENDA team
recombinant
-
-
Manually annotated by BRENDA team
thalamus COMT isoform
UniProt
Manually annotated by BRENDA team
variants 108M and 108V
-
-
Manually annotated by BRENDA team
wild type and variant isoform
-
-
Manually annotated by BRENDA team
; Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
both S-COMT and MB-COMT
-
-
Manually annotated by BRENDA team
Dahl salt-sensitive rats
-
-
Manually annotated by BRENDA team
gene expression in Escherichia coli
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
particulate enzyme
-
-
Manually annotated by BRENDA team
Rattus norvegicus S-COMT
S-COMT
-
-
Manually annotated by BRENDA team
Streptomyces griseus S-COMT
S-COMT
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
knockdown of COMT expression in endometrial glandular cells results in increased estrogenic milieu and increased estrogen-induced cell proliferation, and increases the propensity of estrogen or catecholestrogens to induce reactive oxygen species, microsatellite instability, and neoplastic transformation of endometrial glandular cells
malfunction
-
lack of S-COMT does not affect the levels of L-DOPA in plasma or peripheral tissues, whereas in the full COMT-knock-out mice, these levels are increased. The total COMT activity in the S-COMT-deficient mice is 22-47% of that in the wild type mice. In S-COMT-deficient mice, MB-COMT in the liver and the duodenum is able to O-methylate about one-half of exogenous L-Dopa
metabolism
-
concerted action of cytosolic sulfotransferase SULT1A3 and COMT in dopamine metabolism
physiological function
-
catechol-O-methyltransferase COMT2 is essential for auditory function
physiological function
-
COMT gene expression plays a critical role in modulating the hormonal and carcinogenic effects of estrogen and catecholestrogens and, consequently, modifies the risk for estrogen-induced endometrial cancer
physiological function
-
COMT over expression stabilizes microtubules, ameliorates 17beta-estradiol-induced proliferation, inhibits estrogen receptor alpha and progesterone receptor signaling, and reduces hypoxia-inducible factor-1alpha and tissue necrosis factor-alpha-induced aromatase (CYP19) expression in human uterine leiomyoma cells
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(+)-epicatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
(-)-epicatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
(-)-epigallocatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
(-)-epigallocatechin-3-O-gallate + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
(-)-epigallocatechin-3-O-gallate + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
poor substrate for methylation
-
-
?
(R)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
(R)-3,4-dihydroxymethamphetamine + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
(R)-N-ethyl-3,4-dihydroxyamphetamine + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
(S)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
(S)-3,4-dihydroxymethamphetamine + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
(S)-N-ethyl-3,4-dihydroxyamphetamine + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
1-carboxy-1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
MB-COMT methylates both 2-hydroxyestradiol and 4-hydroxyestradiol at comparable rates, S-COMT methylates 2-hydroxyestradiol roughly twice as fast as it methylates 4-hydroxyestradiol
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 2-methoxyestradiol + 2-hydroxy-3-methoxyestradiol
show the reaction diagram
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
2-hydroxyestradiol 3-methyl ether + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
2-methoxyestradiol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
2-hydroxyestradiol-17beta + S-adenosyl-L-methionine
2-methoxyestradiol-17beta + 2-hydroxyestradiol-17beta methyl ether + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
2-hydroxyestrogen + S-adenosyl-L-methionine
2-methoxyestrogen + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
2-hydroxyestrone + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
the production of 2-methoxyestrone in cultures treated with 2-hydroxyestrone is approximately 2fold that of 4-methoxyestrone in cultures treated with 4-hydroxyestrone
-
-
?
3,4-dihydroxybenzoic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxybenzoic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxybenzoic acid + S-adenosyl-L-methionine
3-hydroxy-4-methoxybenzoic acid + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3,4-dihydroxybenzoic acid + S-adenosyl-L-methionine
4-hydroxy-3-methoxybenzoic acid + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3,4-dihydroxymandelic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxyphenylacetic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxyphenylacetic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
-
3,4-dihydroxyphenylacetic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
3,5-dinitrocatechol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
3-hydroxytyramine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-methoxytyramine
show the reaction diagram
-
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
(17beta)-estra-1(10),2,4-triene-3,4,17-triol + S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
MCF-10F cells oxidize 4-hydroxyestradiol to estrone (estradiol)-3,4-quinones, which react with DNA to form the depurinating N3Ade and N7Gua adducts
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
in the mammary gland, catechol estrogens are predominately inactivated by catechol-O-methyltransferase. in the isoflavone-induced. The estrogen receptor is involved in the down-regulation of COMT expression
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
MB-COMT methylates both 2-hydroxyestradiol and 4-hydroxyestradiol at comparable rates, S-COMT methylates 2-hydroxyestradiol roughly twice as fast as it methylates 4-hydroxyestradiol
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
4-hydroxyestrogen + S-adenosyl-L-methionine
4-methoxyestrogen + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
4-hydroxyestrone + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
4-nitrocatechol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
Streptomyces griseus, Streptomyces griseus S-COMT
-
-
-
-
?
6,7-dihydroxycoumarin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
Streptomyces griseus, Streptomyces griseus S-COMT
-
-
-
-
?
adrenaline + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
adrenaline + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
Rattus norvegicus S-COMT
-
-
-
-
?
adrenaline + S-adenosyl-L-methionine
methanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
aesculetin + S-adenosyl-L-methionine
scopoletin + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
benzene-1,2-diol + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
benzene-1,2-diol + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
P22734
-
-
-
?
caffeic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
caffeic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
Streptomyces griseus, Streptomyces griseus S-COMT
-
-
-
-
?
catechol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
catechol + S-adenosyl-L-methionine
guaiacol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
catecholestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
catecholestrone + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
DL-3,4-dihydroxyamphetamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
DL-3,4-dihydroxyephedrine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
dobutamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
dopa + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
dopa + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-O-methyldopamine
show the reaction diagram
-
-
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
epinine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
esculetin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
esculetin + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
fisetin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
homoprotocatechuic acid + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
L-Dopa + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-O-methyldopa
show the reaction diagram
-
-
-
-
?
L-Dopa + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-O-methyldopa
show the reaction diagram
-
-
-
-
?
L-Dopa + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-O-methyldopa
show the reaction diagram
-
-
-
-
?
L-dopa + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
noradrenaline + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + normetanephrine
show the reaction diagram
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + normetanephrine
show the reaction diagram
-
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + normetanephrine
show the reaction diagram
-
-
-
-
?
p-nitrocatechol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
protocatechualdehyde + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
protocatechuic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
quercetin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-homocysteine + 4''-O-methyl epigallocatechin gallate
S-adenosyl-L-homocysteine + 4',4''-di-O-methyl epigallocatechin gallate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 1,2-dihydroxyphenanthrene
S-adenosyl-L-homocysteine + 1-methoxy-2-hydroxyphenanthrene + 1-methoxy-2-hydroxyphenanthrene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 1-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 1-hydroxypyrene
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2,3-dihydroxybenzaldehyde
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2,3-dihydroxynaphthalene
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-(1-thienyl)ethyl-3,4-dihydroxybenzylcyano acetate
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxy-L-Phe
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxyacetophenone
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxybenzoic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxybenzoic acid ethyl ester
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxymandelic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxyphenylacetic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxyphenylglycol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3-fluorocatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3-methoxy-5-bromocatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3-methoxycatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-chlorocatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-hydroxyequilenin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-isopropylcatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-methylcatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-nitrocatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-tert-butyl-5-methoxycatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-tert-butylcatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 5-hydroxydopamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-hydroxydopa
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-hydroxydopamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a catechol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a catechol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a catechol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + adrenaline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + anthrarobin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + carbidopa
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + catechin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + catechin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + catechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + chlorogenic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + dihydrexidine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + dobutamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + dopamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epicatechin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epicatechin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + epicatechin gallate
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin gallate
S-adenosyl-L-homocysteine + 4''-O-methyl epigallocatechin gallate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin gallate
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin-3-gallate
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epinephrine
S-adenosyl-L-homocysteine + metanephrine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epinephrine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + epinephrine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
P22734
-
-
-
?
S-adenosyl-L-methionine + esculetin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + ethyl-3,4-dihydroxybenzylcyanoacetate
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + fisetin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + gallic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + isoproterenol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + L-Dopa
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + L-Dopa
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + levodopa
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + methyl gallate
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + noradrenaline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
P22734
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + normetanephrine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + pyrene
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + pyrogallol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + quercetin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
membrane-bound enzyme form MB-COMT, soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + R-salsolinol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + rosmarinic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + salsoline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + salsoline-1-carboxylic acid
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + scopoletin
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + SKF38393
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + tetrachlorocatechol
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
L-dopa + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
P22734
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
benzimidazole
-
-
-
additional information
?
-
-
not: monophenols
-
-
-
additional information
?
-
-
not: monophenols
-
-
-
additional information
?
-
-
strict requirement for S-adenosyl-L-methionine as methyl donor and a catechol as acceptor substrate
-
-
-
additional information
?
-
-
activity in cells expressing norepinephrine transporter
-
-
-
additional information
?
-
-
comparison of wild type and variant isoforms and implications for estrogen levels
-
-
-
additional information
?
-
-
physiological role is the inactivation of catecholamine hormones and neurotransmitters as well as detoxification of a variety of xenobiotic amines and drugs
-
-
-
additional information
?
-
-
membrane protein and (or) lipid components may play an important role in catecholamine metabolism
-
-
-
additional information
?
-
-
primary role in extraneuronal inactivation of endogenous catecholamines and in the further metabolism of oxidized catecholamine metabolites
-
-
-
additional information
?
-
-
COMT in the adrenal gland might not be related to blood pressure regulation
-
-
-
additional information
?
-
-
constitutive enzyme may play an important role in detoxification of polycyclic aromatic hydrocarbons
-
-
-
additional information
?
-
-
key enzyme in the elemination of dopamine in the prefrontal cortex of the human brain. Genetic variation in COMT gene (MIM 116790) is associated with altered prefrontal cortex function and higher risk for schizophrenia. A common single-nucleotide polymorphism within COMT, Val158Met, significantly affects protein abundance and enzyme activity but not mRNA expression levels. Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function
-
-
-
additional information
?
-
-
the enzyme plays an important role in the inactivation potentially genotoxic catechol estrogens
-
-
-
additional information
?
-
-
increased COMT enzyme activity in transgenic mice overexpressing a human COMT-Val polymorphism (Val-tg mice) results in disrupted attentional set-shifting abilities, and impaired working and recognition memory, but blunted stress responses and pain sensitivity. COMT disruption improves working memory, but increased stress responses and pain sensitivity. The COMT gene has a critical role in an apparent evolutionary trade-off between cognitive and affective functions
-
-
-
additional information
?
-
-
prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism
-
-
-
additional information
?
-
-
While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. Catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4-hydroxyestradiol + S-adenosyl-L-methionine
(17beta)-estra-1(10),2,4-triene-3,4,17-triol + S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
MCF-10F cells oxidize 4-hydroxyestradiol to estrone (estradiol)-3,4-quinones, which react with DNA to form the depurinating N3Ade and N7Gua adducts
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
in the mammary gland, catechol estrogens are predominately inactivated by catechol-O-methyltransferase. in the isoflavone-induced. The estrogen receptor is involved in the down-regulation of COMT expression
-
-
?
S-adenosyl-L-methionine + a catechol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a catechol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a catechol
?
show the reaction diagram
-
-
-
-
?
homoprotocatechuic acid + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
activity in cells expressing norepinephrine transporter
-
-
-
additional information
?
-
-
comparison of wild type and variant isoforms and implications for estrogen levels
-
-
-
additional information
?
-
-
physiological role is the inactivation of catecholamine hormones and neurotransmitters as well as detoxification of a variety of xenobiotic amines and drugs
-
-
-
additional information
?
-
-
membrane protein and (or) lipid components may play an important role in catecholamine metabolism
-
-
-
additional information
?
-
-
primary role in extraneuronal inactivation of endogenous catecholamines and in the further metabolism of oxidized catecholamine metabolites
-
-
-
additional information
?
-
-
COMT in the adrenal gland might not be related to blood pressure regulation
-
-
-
additional information
?
-
-
constitutive enzyme may play an important role in detoxification of polycyclic aromatic hydrocarbons
-
-
-
additional information
?
-
-
key enzyme in the elemination of dopamine in the prefrontal cortex of the human brain. Genetic variation in COMT gene (MIM 116790) is associated with altered prefrontal cortex function and higher risk for schizophrenia. A common single-nucleotide polymorphism within COMT, Val158Met, significantly affects protein abundance and enzyme activity but not mRNA expression levels. Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function
-
-
-
additional information
?
-
-
the enzyme plays an important role in the inactivation potentially genotoxic catechol estrogens
-
-
-
additional information
?
-
-
increased COMT enzyme activity in transgenic mice overexpressing a human COMT-Val polymorphism (Val-tg mice) results in disrupted attentional set-shifting abilities, and impaired working and recognition memory, but blunted stress responses and pain sensitivity. COMT disruption improves working memory, but increased stress responses and pain sensitivity. The COMT gene has a critical role in an apparent evolutionary trade-off between cognitive and affective functions
-
-
-
additional information
?
-
-
prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism
-
-
-
additional information
?
-
-
While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. Catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
-
can substitute for Mg2+
Co2+
-
Co2+ and Mn2+ most effective in activation
Fe2+
-
can substitute for Mg2+
Mg2+
-
-
Mg2+
-
below 2 mM; inhibition above 2 mM; required
Mg2+
-
optimum range: 2-5 mM; required
Mg2+
-
required
Mg2+
-
optimum 10 mM; required
Mg2+
-
required
Mg2+
-
required
Mg2+
-
Km: 0.22 mM for soluble enzyme, 0.17 mM for membrane-bound enzyme
Mg2+
-
Km: 0.21 mM for soluble activity, Km: 0.15 mM for membrane-bound activity
Mg2+
-
Mg2+ is a necessary cofactor for the methylation reaction, it is octahedrally coordinated in the active site by the side chains of D141, D169, N170, the two-hydroxyl groups of the catechol substrate, and a water molecule trans to N170
Mn2+
-
Co2+ and Mn2+ most effective in activation
Ni2+
-
can substitute for Mg2+
Zn2+
-
can substitute for Mg2+
Zn2+
-
can substitute for Mg2+
additional information
-
activity of the enzyme is strongly influenced by the nature of the buffer
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-epicatechin-3-gallate
-
IC50: 0.0002 mM with 2-hydroxyestradiol as substrate, IC50: 0.0003 mM with 4-hydroxyestradiol as substrate
(-)-epigallocatechin
-
IC50: 0.044 mM with 2-hydroxyestradiol as substrate, IC50: 0.05 nM with 4-hydroxyestradiol as substrate
(-)-epigallocatechin gallate
-
potent inhibitor with epigallocatechin or 3,4-dihydroxy-L-Phe as substrates
(-)-epigallocatechin gallate-4''-O-glucuronide
-
with epigallocatechin or 3,4-dihydroxy-L-Phe as substrates
(-)-epigallocatechin gallate-7-O-glucuronide
-
with epigallocatechin or 3,4-dihydroxy-L-Phe as substrates
(-)-epigallocatechin-3-gallate
-
IC50: 70 nM with 2-hydroxyestradiol as substrate, IC50: 80 nM with 4-hydroxyestradiol as substrate, mixed inhibitor
(-)-epigallocatechin-3-gallate
-
-
(-)-epigallocatechin-3-gallate-3''-O-glucuronide
-
IC50: 0.002 mM with 2-hydroxyestradiol as substrate, IC50: 0.0025 mM with 4-hydroxyestradiol as substrate
(-)-epigallocatechin-3-gallate-3'-O-glucuronide
-
IC50: 0.0018 mM with 2-hydroxyestradiol as substrate, IC50: 0.0023 mM with 4-hydroxyestradiol as substrate
(-)-epigallocatechin-3-gallate-4''-O-glucuronide
-
IC50: 0.0025 mM with 2-hydroxyestradiol as substrate, IC50: 0.004 mM with 4-hydroxyestradiol as substrate
(-)-epigallocatechin-3-gallate-7-O-glucuronide
-
IC50: 600 nM with 2-hydroxyestradiol as substrate, IC50: 800 nM with 4-hydroxyestradiol as substrate
(-)-epigallocatechin-3-O-gallate
-
IC50: 0.05-0.07 nM for the O-methylation of 2-hydroxyestradiol, IC50: 200-500 nM for O-methylation of 4-hydroxyestradiol
(-)-epigallocatechin-3-O-gallate
-
potent non-competitive inhibitor
(-)-epigallocatechin-3-O-gallate
-
-
(-)epicatechin
-
IC50: 0.06 mM with 2-hydroxyestradiol as substrate, IC50: 0.08 mM with 4-hydroxyestradiol as substrate
(-)epicatechin gallate3,5-dinitrocatechol
-
with epigallocatechin or 3,4-dihydroxy-L-Phe as substrates
(2-amino-3-methylbutanoyloxy)methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
(2E)-4,7-anhydro-1,2,3-trideoxy-1-(2,3-dihydroxy-5-nitrobenzamido)-L-ribo-hept-2-enitol
-
-
(2R,3R)-5,7-bis(acetyloxy)-2-[3,4,5-tris(acetyloxy)phenyl]-3,4-dihydro-2H-chromen-3-yl 3,4-bis(acetyloxy)-5-(2-oxopropyl)benzoate
-
-
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,4,5-trihydroxybenzoate)
-
-
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,5-dihydroxybenzoate)
-
-
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis[3,4,5-tris(acetyloxy)benzoate]
-
-
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis[3,5-bis(acetyloxy)benzoate]
-
-
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
1,2-dihydroxy-4-[2-(methylamino)butyl]benzene
-
uncompetitive inhibitor of the sCOMT isoform
1-(butyryloxy)ethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
1-(isobutyryloxy)ethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
1-Carboxysalsoline
-
i.e. 1-carboxy-1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, competitive inhibition of 3,4-dihydroxybenzoic acid methylation
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-4-(trifluoromethyl)-1H-imidazole
-
-
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]benzo[d]imidazole
-
-
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]pyridin-4(1H)-one
-
-
1-[3,4-dihydroxy-5-nitrophenyl]-2-phenyl-ethanone
-
-
2-Hydroxyestradiol-17beta 3-methyl ether
-
product inhibition
2-hydroxyoestrogen
-
-
2-Iodosobenzoic acid
-
-
2-methoxyestradiol-17beta
-
product inhibition
3,4,5-trihydroxypyrogallol
-
liver homogenate, 0.03 mM inhibitior: 0.8% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
3,4-dihydroxymethamphetamine
-
uncompetitive inhibitor of the sCOMT isoform
3,5-dinitrocatechol
-
liver S-COMT, 50% inhibition at 74 nM
3,5-dinitrocatechol
-
uncompetitive inhibitor
3-Carboxysalsolinol
-
-
3-chloro-5,6-dihydroxy-7-nitro-1-benzothiophene-2-carboxylic acid
-
-
3-fluoro-4-[1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl]benzene-1,2-diol
-
liver homogenate, 0.03 mM inhibitior: 32.3% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
3-nitro-5-(1-p-tolyl-1H-pyrazol-5-yl)benzene-1,2-diol
-
liver homogenate, 0.003 mM inhibitior: 0% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
3-nitro-5-(1-phenyl-1H-pyrazol-5-yl)benzene-1,2-diol
-
liver homogenate, 0.003 mM inhibitior: 0% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
3-nitro-5-(1H-pyrazol-5-yl)benzene-1,2-diol
-
liver homogenate, 0.003 mM inhibitior: 0% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
4''-O-methyl epigallocatechin gallate
-
potent inhibitor with epigallocatechin or 3,4-dihydroxy-L-Phe as substrates
4',3'',4''-tri-O-methyl epigallocatechin gallate
-
substrate: epigallocatechin
4',4''-di-O-methyl epigallocatechin gallate
-
potent inhibitor with epigallocatechin or 3,4-dihydroxy-L-Phe as substrates
4'-4''-di-O-methyl-epigallocatechin-3-gallate
-
IC50: 0.00015 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate, competitive with respect S-adenyosylmethionine, noncompetitive with respect to catechol
4'-fluoro-4,5-dihydroxy-biphenyl-3-carboxylic acid [(E)-3-[(2S,4R,5R)-4-hydroxy-5-(6-methyl-purin-9-yl)-tetrahydro-furan-2-yl]-allyl]-amide
P22734
-
4'-fluoro-4,5-dihydroxy-biphenyl-3-carboxylic acid [(E)-3-[(2S,4R,5R)-4-hydroxy-5-(6-methylamino-purin-9-yl)-tetrahydro-furan-2-yl]-allyl]-amide
P22734
-
4'-O-methyl-(-)-epigallocatechin
-
IC50: 0.032 mM with 2-hydroxyestradiol as substrate, IC50: 0.04 mM with 4-hydroxyestradiol as substrate
4'-O-methyl-epigallocatechin-3-gallate
-
IC50: 0.0001 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
4-(1-phenyl-1H-pyrazol-5-yl)benzene-1,2,3-triol
-
liver homogenate, 0.03 mM inhibitior: 26.8% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
4-(5-(3,4-dihydroxy-5-nitrophenyl)-1H-pyrazol-1-yl)benzonitrile
-
liver homogenate, 0.003 mM inhibitior: 0.3% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
4-(tert-octyl)phenol
-
causes significant inhibition of enzyme activity
4-hydroxyequilenin
-
inhibits its own methylation by COMT at higher concentrations in the presence of the reducing agent dithiothreitol, irreversible inhibitor, the inhibitor causes formation of intermolecular disulfide bonds, cys33 in recombinant human soluble COMT is the residue most likely modified by the inhibitor
4-nitrocatechol
-
-
4-phenyl-7,8-dihydroxycoumarin
-
-
4-[1-(4-methylphenyl)-1H-pyrazol-5-yl]benzene-1,2-diol
-
liver homogenate, 0.03 mM inhibitior: 41.2% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
4-[4-(4-chlorophenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,2,3-triol
-
liver homogenate, 0.003 mM inhibitior: 15.6% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
5-(1-methyl-1H-pyrazol-5-yl)-3-nitrobenzene-1,2-diol
-
liver homogenate, 0.003 mM inhibitior: 1.1% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
5-Substituted 3-hydroxy-4-methoxybenzaldehydes
-
-
5-Substituted 3-hydroxy-4-methoxybenzoic acids
-
-
5-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-5H-imidazo[4,5-c]pyridine
-
-
5-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-5H-pyrrolo[3,2-c]pyridine
-
-
5-[1-(3-chlorophenyl)-1H-pyrazol-5-yl]-2,3-dihydroxybenzoic acid
-
liver homogenate, 0.03 mM inhibitior: 24.1% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
5-[1-(3-chlorophenyl)-1H-pyrazol-5-yl]-3-nitrobenzene-1,2-diol
-
liver homogenate, 0.003 mM inhibitior: 0% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
5-[1-(3-chlorophenyl)-4-phenyl-1H-pyrazol-5-yl]-3-nitrobenzene-1,2-diol
-
liver homogenate, 0.003 mM inhibitior: 68.6% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
6-methyl-9-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]purine
-
-
9-[(5E)-3,5,6,7-tetradeoxy-3-fluoro-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-xylo-hept-5-enofuranosyl]-N6-methyladenine
P22734
-
9-[(5E)-3,5,6,7-tetradeoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-3-methyl-beta-D-xylo-hept-5-enofuranosyl]-N6-propyladenine
P22734
-
9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]purine
-
-
Amino group reagents
-
-
-
Analogs of S-adenosyl-L-homocysteine
-
overview: inhibition of the liver, heart and brain enzyme
ascorbic acid
-
-
benzyl butyl phthalate
-
causes significant inhibition of enzyme activity
benzyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
beta-thujaplicin
-
70-100% inhibition at 0.2 mM
butyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
butyryloxymethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
Ca2+
-
-
caffeic acid
-
-
caffeic acid
-
COMT from liver, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from liver, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from placenta, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from placenta, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C
caffeic acid phenethyl ester
-
COMT from liver, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from liver, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C
catechin
-
IC50: 14-17 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.005-0.007 mM for O-methylation of 4-hydroxyestradiol
catechin
-
IC50: 0.00164 mM
catechol
-
-
CGP 28014
-
-
chlorogenic acid
-
COMT from liver, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from liver, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from placenta, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C; COMT from placenta, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37C
chrysin
-
slight inhibition at 0.3 mM
Cistus parviflorus leaf extract
-
mixed type inhibition
-
daidzein
-
soy isoflavones at hormonally active concentrations cause a significant reduction of both COMT mRNA levels and COMT activity as well as of the methylation of 4-hydroxyestradiol
dibutyl phthalate
-
causes significant inhibition of enzyme activity
diisononyl phthalate
-
causes significant inhibition of enzyme activity
dioctyl phthalate
-
causes significant inhibition of enzyme activity
dobutamine
-
competitive to dopamine
dopamine
-
competitive to dobutamine
entacapone
-
-
epicatechin
-
IC50: 44-65 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.01-0.018 mM for O-methylation of 4-hydroxyestradiol
epicatechin
-
IC50: 0.00196 mM
fisetin
-
IC50: 0.0033-0.0045 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.0026-0.0042 nM for O-methylation of 4-hydroxyestradiol
flavone
-
IC50: 0.00549 mM
Flavonoids
-
overview: relationship between structure and ability to inhibit
-
gallic acid
-
-
gallic acid
-
-
gallic acid
-
-
Gallic acid methylester
-
-
genistein
-
slight inhibition at 0.3 mM
genistein
-
soy isoflavones at hormonally active concentrations cause a significant reduction of both COMT mRNA levels and COMT activity as well as of the methylation of 4-hydroxyestradiol
Hg2+
-
complete inhibition at 1 mM
High ionic strength
-
-
-
homocysteine
-
-
iodoacetamide
-
slight
iodoacetic acid
-
-
isobutyryloxymethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
isopropyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
L-ascorbic acid
-
-
L-ascorbic acid
-
-
methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
Mg2+
-
inhibition above 2 mM; required for activity
Mg2+
-
required for activity
Mg2+
-
required for activity
Mg2+
-
required for activity
N-(2-[2-[(2R,3S,4R,5R)-5-(6-amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-ethoxy]-ethyl)-2,3-dihydroxy-5-nitro-benzamide
-
IC50: 0.002 mM
N-(3,4-Dihydroxyphenyl)maleimide
-
irreversible
N-(3,4-Dihydroxyphenyl)succinimide
-
reversible
N-ethyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-imidazole-4-carboxamide
-
-
N-ethyl-3,4-dihydroxyamphetamine
-
uncompetitive inhibitor of the sCOMT isoform
N-ethylmaleimide
-
-
N-ethylmaleimide
-
70-100% inhibition at 0.2 mM
N-ethylmaleimide
-
complete inhibition at 1 mM
N-methyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-1,2,4-triazole-3-carboxamide
-
-
N-methyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-imidazole-4-carboxamide
-
-
N-[(2E)-3-[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(methylamino)-9H-purin-9-yl]tetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
-
N-[(2E)-3-[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(propylamino)-9H-purin-9-yl]tetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
-
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
-
-
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
-
-
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-ethyl-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
-
N-[(2E)-3-[(2R,3S,4R,5R)-5-[6-(cyclopropylamino)-9H-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
-
N-[(2E)-3-[(2R,3S,4R,5R)-5-[6-(ethylamino)-9H-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
-
N-[(2E)-3-[(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-3-hydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
P22734
-
N-[(2E)-3-[(2S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
P22734
-
N-[(E)-4-[(2R,3S,4R,5R)-5-(6-Amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-but-2-enyl]-2,3-dihydroxy-5-nitro-benzamide
-
IC50: 9 nM
N-[2-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]ethyl]-2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 60 nM
N-[3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]propyl]2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 200 nM
N-[4-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]butyl]-2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 0.005 mM
N-[[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyl]-2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 0.09 mM, very potent bisubstrate inhibitor
N6-methyl-9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]adenine
-
-
nebicapone
-
-
nitecapone
-
-
nordihydroguaiaretic acid
-
-
norepinephrine
-
0.01 mM, 41% inhibition of 2-hydroxyestradiol methylation
OR-462
-
disubstituted catechol
OR486
-
depressed COMT activity results in enhanced mechanical and thermal pain sensitivity
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
complete inhibition at 1 mM
p-hydroxymercuribenzoate
-
70-100% inhibition at 0.2 mM
Peganum harmala seed extract
-
mixed type inhibition
-
Phenolic compounds
-
-
-
Polyphenolic compounds
-
-
-
propyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
Purpurogallin
-
-
Purpurogallin
-
decreased Vmax and increased Km-value
purpurogallin carboxylic acid
-
-
pyridin-4-yl (5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-1-thio-beta-D-ribo-hept-5-enofuranoside
-
-
pyrogallol
-
70-100% inhibition at 0.2 mM
pyrogallol
-
-
pyrogallol
-
-
pyrogallol
-
-
quercetin
-
IC50: 0.0085 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
quercetin
-
IC50: 0.0009-0.0015 mM for the O-methylation of 2-hydroxyestradiol, IC50: 0.0005-0.0012 mM for O-methylation of 4-hydroxyestradiol
quercetin
-
0.01 mM, 90% inhibition of 2-hydroxyestradiol methylation
quercetin
-
IC50: 0.00048 mM
Ro 41-0960
-
-
Ro 41-0960
-
IC50: 5-42 nM
Ro 41-0960
-
-
RO-4-4602
-
competitive
Ro41-0960
-
blocks the methoxylation of catechol estrogens, with concomitant 3fold to 4fold increases in the levels of the depurinating adducts. Low activity of COMT leads to higher levels of depurinating estrogen-DNA adducts that can induce mutations and initiate cancer
Ro41-0960
-
-
Ro41-0960
-
depressed COMT activity results in enhanced mechanical and thermal pain sensitivity
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
50% inhibition at about 0.005 mM
S-adenosyl-L-methionine
-
-
Salsolidine
-
i.e. 1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, competitive inhibition of 3,4-dihydroxybenzoic acid methylation
Salsolidine
-
-
theaflavin-3,3'-digallate
-
decreased Vmax and increased Km-value
tolcapone
-
-
tolcapone
-
possibility of genotype-targeted pharmacology for the treatment of cognitive dysfunction associated with schizophrenia. Even though tolcapone has proved useful in this regard, its hepatotoxicity proscribes its wide-spread use. The development of COMT inhibitors that can permeate the blood-brain barrier effectively and are devoid of serious adverse effects will allow expansion of the search for more specific, selective and effective therapies for the treatment of cognitive disorders
Triton X-100
-
-
tropolone
-
70-100% inhibition at 0.2 mM
tropolone
-
-
tropolone
-
complete inhibition at 0.25 mM
U-0521
-
-
Vitex agnus-cactus leaf extract
-
mixed type inhibition
-
[5-(3,4-dihydroxy-5-nitrophenyl)-4-phenyl-1H-pyrazol-1-yl](4-methylphenyl)methanone
-
liver homogenate, 0.003 mM inhibitior: 2.8% metanephrine formed relative to the control in absence of inhibitor (5 min reaction time), pH 7.8, 37C
Mg2+
-
required for activity
additional information
-
inhibition by analogs of S-adenosyl-homcysteine
-
additional information
-
relationship between the structure of flavonoids and their inhibitory activity
-
additional information
-
substrate inhibition is dependent on the concentration of S-adenosylmethionine and MgCl2
-
additional information
-
activity of the enzyme is strongly influenced by the nature of the buffer
-
additional information
-
no inhibition by genistein, daidzein and biochanin A
-
additional information
-
role of COMT inhibitors in Parkinsons disease as a new therapeutic approach to Parkinsons disease involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. A historical overview of the discovery and development of COMT inhibitors is presented with a special emphasis on nebicapone, presently under clinical development, as well as entacapone and tolcapone, which are already approved as adjuncts in the therapy of Parkinsons disease. This article reviews human pharmacokinetic and pharmacodynamic properties of these drugs as well as their clinical efficacy and safety
-
additional information
-
COMT is a target for inhibitor development aiming at Parkinsons disease treatment and is submitted to extensive structure-based drug design
-
additional information
-
(-)-epigallocatechin is not active even at a concentration of 0.05 mM
-
additional information
-
COMT activity appears unaffected by loss of the dopaminergic nigrostriatal pathway and levodopa treatment
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cysteine
-
20 mM, activates
cysteine
-
required
additional information
-
activity of the enzyme is strongly influenced by the nature of the buffer
-
additional information
-
L-dopa induces expression and activity of enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0022 - 0.0082
(-)-epicatechin
-
-
0.0039 - 0.0067
(-)-epigallocatechin
-
-
0.02
(R)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.03
(R)-3,4-dihydroxymethamphetamine
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.09
(R)-N-ethyl-3,4-dihydroxyamphetamine
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.02
(S)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.03
(S)-3,4-dihydroxymethamphetamine
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.07
(S)-N-ethyl-3,4-dihydroxyamphetamine
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.000148
2-hydroxyestradiol
-
male heart
0.00015
2-hydroxyestradiol
-
membrane-bound enzyme form
0.000215
2-hydroxyestradiol
-
female heart
0.00027
2-hydroxyestradiol
-
soluble enzyme form
0.00032
2-hydroxyestradiol
-
-
0.000356
2-hydroxyestradiol
-
female kidney
0.000407
2-hydroxyestradiol
-
male kidney
0.001
2-hydroxyestradiol
-
COMT from placenta, in Tris-HCl buffer (10mM, pH 7.4), at 37C
0.0032
2-hydroxyestradiol
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.0036
2-hydroxyestradiol
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.0175
2-hydroxyestradiol
-
-
0.014
2-hydroxyestradiol-17beta
-
-
0.64
3,4-dihydroxyphenylacetic acid
-
-
0.0024
4-hydroxyequilenin
-
pH 7.8
0.00037
4-hydroxyestradiol
-
-
0.0035
4-hydroxyestradiol
-
COMT from placenta, in Tris-HCl buffer (10mM, pH 7.4), at 37C
0.0045
4-hydroxyestradiol
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.0064
4-hydroxyestradiol
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.0161
4-hydroxyestradiol
-
-
0.5
6,7-dihydroxycoumarin
-
-
0.0014
adrenaline
-
brain MB-COMT, native
0.0025
adrenaline
-
liver MB-COMT, native
0.0093
adrenaline
-
liver MB-COMT, solubilized
0.012
adrenaline
-
brain MB-COMT, solubilized
0.257
adrenaline
-
liver S-COMT, native
0.292
adrenaline
-
brain S-COMT, native
0.295
adrenaline
-
liver S-COMT, detergent-treated
0.428
adrenaline
-
S-COMT, recombinant fusion protein
0.48
adrenaline
-
brain S-COMT, detergent-treated
0.0064
aesculetin
-
pH 7.4, 37C
0.0022
catechin
-
MB-COMT, 0.25 mM S-adenosyl-L-methionine
0.0089
catechin
-
S-COMT, 0.25 mM S-adenosyl-L-methionine
0.01
catechol
-
recombinant enzyme expressed in Escherichia coli, membrane-bound enzyme form
0.1
catechol
-
pH not specified in the publication, temperature not specified in the publication
0.108
catechol
-
recombinant enzyme expressed in Escherichia coli, soluble enzyme form
0.145
catechol
-
pH not specified in the publication, temperature not specified in the publication
0.725
catechol
-
pH not specified in the publication, temperature not specified in the publication
0.833
catechol
-
pH not specified in the publication, temperature not specified in the publication
0.0006
Catecholestradiol
-
-
0.0012
Catecholestrone
-
-
0.05
dobutamine
-
-
0.0005
dopamine
-
-
0.0033
dopamine
-
-
0.0033
dopamine
-
membrane-bound enzyme form, brain
0.015
dopamine
-
recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form
0.017
dopamine
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.207
dopamine
-
recombinant enzyme expressed in Sf9 cells, soluble enzyme form
0.2632
dopamine
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.28
dopamine
-
soluble enzyme form, brain
0.44
dopamine
-
-
0.0043
epicatechin
-
MB-COMT, 0.25 mM S-adenosyl-L-methionine
0.0257
epicatechin
-
S-COMT, 0.25 mM S-adenosyl-L-methionine
0.0081
epigallocatechin
-
-
0.0117
epigallocatechin
-
-
0.00017
epigallocatechin gallate
-
-
0.004
epigallocatechin gallate
-
-
0.0048
epigallocatechin gallate
-
-
0.0009 - 0.003
epinephrine
-
membrane-bound enzyme form
0.009
epinephrine
-
membrane-bound activity
0.012
epinephrine
-
membrane-bound enzyme form
0.0288
epinephrine
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.12
epinephrine
-
-
0.168 - 0.345
epinephrine
-
soluble enzyme form
0.242
epinephrine
-
soluble enzyme form
0.276
epinephrine
-
recombinant enzyme
0.3947
epinephrine
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.59 - 1
epinephrine
-
soluble activity
0.0062
esculetin
-
-
0.0015
fisetin
-
S-COMT, 0.25 mM S-adenosyl-L-methionine
0.00091
isoproterenol
-
membrane-bound enzyme form
0.121
isoproterenol
-
soluble enzyme form
0.266
levodopa
-
recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form
0.0055 - 0.114
norepinephrine
-
membrane-bound enzyme form
0.0055
norepinephrine
-
corebral cortex, membrane-bound form
0.00587
norepinephrine
-
cerebellum, membrane-bound form
0.00837
norepinephrine
-
brain stem, membrane-bound form
0.00912
norepinephrine
-
hippocampus, membrane-bound form
0.0105
norepinephrine
-
hypophysis, membrane-bound form
0.0114
norepinephrine
-
hypothalamus, membrane-bound form
0.024
norepinephrine
-
recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form
0.0306
norepinephrine
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.169
norepinephrine
-
heart
0.224
norepinephrine
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.276
norepinephrine
-
brain
0.304 - 0.464
norepinephrine
-
soluble enzyme form
0.304
norepinephrine
-
corebral cortex, soluble enzyme
0.305
norepinephrine
-
hippocampus, soluble enzyme
0.313
norepinephrine
-
cerebellum, soluble enzyme
0.369
norepinephrine
-
recombinant enzyme expressed in Sf9 cells, soluble enzyme form
0.39
norepinephrine
-
brain stem, soluble enzyme
0.443
norepinephrine
-
hypothalamus, soluble enzyme
0.465
norepinephrine
-
hypophysis, soluble enzyme
1.856
norepinephrine
-
liver
0.0038
p-nitrocatechol
-
-
0.0015
quercetin
-
S-COMT, 0.25 mM S-adenosyl-L-methionine
0.0061
quercetin
-
-
0.0069
quercetin
-
-
0.043
R-salsolinol
-
membrane-bound enzyme form
0.156
R-salsolinol
-
soluble enzyme form
0.0031
S-adenosyl-L-methionine
-
-
0.0031
S-adenosyl-L-methionine
-
cosubstrate esculetin
0.0035
S-adenosyl-L-methionine
-
pH 7.4, 37C
0.00501
S-adenosyl-L-methionine
-
membrane-bound activity
0.0058
S-adenosyl-L-methionine
-
cosubstrate: 4-hydroxyestradiol, MB-COMT
0.0061
S-adenosyl-L-methionine
-
-
0.00697
S-adenosyl-L-methionine
-
soluble enzyme
0.00863
S-adenosyl-L-methionine
-
soluble activity
0.0113
S-adenosyl-L-methionine
-
membrane-bound enzyme
0.0144
S-adenosyl-L-methionine
-
cosubstrate: 2-hydroxyestradiol, MB-COMT
0.0172
S-adenosyl-L-methionine
-
-
0.027
S-adenosyl-L-methionine
-
S-COMT, recombinant fusion protein
0.036
S-adenosyl-L-methionine
-
recombinant enzyme
0.04
S-adenosyl-L-methionine
-
cosubstrate esculetin
0.056
S-adenosyl-L-methionine
-
cosubstrate 3,4-dihydroxyphenylacetic acid
0.1136
S-adenosyl-L-methionine
-
cosubstrate: 2-hydroxyestradiol, S-COMT
0.1453
S-adenosyl-L-methionine
-
cosubstrate: 4-hydroxyestradiol, S-COMT
0.283
S-adenosyl-L-methionine
-
-
0.6
S-adenosyl-L-methionine
-
-
0.613
levodopa
-
recombinant enzyme expressed in Sf9 cells, soluble enzyme form
additional information
additional information
-
overview: Km values of liver, heart and brain enzymes with various substrates
-
additional information
additional information
-
-
-
additional information
additional information
-
pH-dependence of Km, methods for kinetic studies
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
kinetics and mechanism
-
additional information
additional information
-
assay method
-
additional information
additional information
-
assay conditions
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.085
2-hydroxyestradiol
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.99
2-hydroxyestradiol
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.1
4-hydroxyequilenin
-
pH 7.8
0.035
4-hydroxyestradiol
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.077
4-hydroxyestradiol
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.18
catechin
-
S-COMT, 0.25 mM S-adenosyl-L-methionine
0.26
catechin
-
MB-COMT, 0.25 mM S-adenosyl-L-methionine
0.088
dopamine
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.19
dopamine
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.17
epicatechin
-
S-COMT, 0.25 mM S-adenosyl-L-methionine
0.315
epicatechin
-
MB-COMT, 0.25 mM S-adenosyl-L-methionine
0.085
epinephrine
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.25
epinephrine
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
0.04
norepinephrine
-
S-COMT, 0.1 mM S-adenosyl-L-methionine
0.18
norepinephrine
-
MB-COMT, 0.1 mM S-adenosyl-L-methionine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00032
(-)-epigallocatechin-3-gallate
-
substrate: 2-hydroxyestradiol
0.00037
(-)-epigallocatechin-3-gallate
-
substrate: 4-hydroxyestradiol
0.000006
(2-amino-3-methylbutanoyloxy)methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.007022
(2E)-4,7-anhydro-1,2,3-trideoxy-1-(2,3-dihydroxy-5-nitrobenzamido)-L-ribo-hept-2-enitol
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0000016
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0000166
1-(butyryloxy)ethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.000017
1-(isobutyryloxy)ethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.44
1-Carboxysalsoline
-
-
0.004645
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-4-(trifluoromethyl)-1H-imidazole
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.014
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]benzo[d]imidazole
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0749
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]pyridin-4(1H)-one
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000019
1-[3,4-dihydroxy-5-nitrophenyl]-2-phenyl-ethanone
-
-
0.0000456
3,5-dinitrocatechol
-
pH 7.4, 37C
0.000001
3-chloro-5,6-dihydroxy-7-nitro-1-benzothiophene-2-carboxylic acid
-
Ki value below 0.000001 mM, pH not specified in the publication, temperature not specified in the publication
0.026
4-hydroxyequilenin
-
pH 7.8, inhibition og methylation of 4-hydroxyestradiol
0.0024
5-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-5H-imidazo[4,5-c]pyridine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.002378
5-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-5H-pyrrolo[3,2-c]pyridine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000001
6-methyl-9-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]purine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000034
9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]purine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0000102
benzyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0000013
butyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0000106
butyryloxymethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0003
entacapone
-
-
0.224
homocysteine
-
-
0.000017
isobutyryloxymethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0000011
isopropyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0000022
methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.0104
N-ethyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-imidazole-4-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0156
N-methyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-1,2,4-triazole-3-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0199
N-methyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-imidazole-4-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000002
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000007
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000007
N6-methyl-9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]adenine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.00102
nitecapone
-
-
0.0000092
propyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
0.07
Purpurogallin
-
-
0.000132
pyridin-4-yl (5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-1-thio-beta-D-ribo-hept-5-enofuranoside
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0053
RO-4-4602
-
plus norepinephrine
0.007
RO-4-4602
-
plus dopamine
0.009
RO-4-4602
-
plus epinephrine
0.001
S-adenosyl-L-homocysteine
-
cosubstrate S-adenosyl-L-methionine
0.007
S-adenosyl-L-homocysteine
-
cosubstrate S-adenosyl-L-methionine
0.022 - 0.04
S-adenosyl-L-homocysteine
-
-
0.039
S-adenosyl-L-homocysteine
-
-
0.19
Salsolidine
-
-
0.00027
tolcapone
-
-
0.005
tropolone
-
plus dopamine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0003
(-)-epicatechin-3-gallate
-
IC50: 0.0002 mM with 2-hydroxyestradiol as substrate, IC50: 0.0003 mM with 4-hydroxyestradiol as substrate
0.044
(-)-epigallocatechin
-
IC50: 0.044 mM with 2-hydroxyestradiol as substrate,
0.05
(-)-epigallocatechin
-
IC50: 0.05 mM with 4-hydroxyestradiol as substrate
0.00007
(-)-epigallocatechin-3-gallate
-
IC50: 70 nM with 2-hydroxyestradiol as substrate
0.00008
(-)-epigallocatechin-3-gallate
-
IC50: 80 nM with 4-hydroxyestradiol as substrate, mixed inhibitor
0.0025
(-)-epigallocatechin-3-gallate-3''-O-glucuronide
-
IC50: 0.002 mM with 2-hydroxyestradiol as substrate, IC50: 0.0025 mM with 4-hydroxyestradiol as substrate
0.0023
(-)-epigallocatechin-3-gallate-3'-O-glucuronide
-
IC50: 0.0018 mM with 2-hydroxyestradiol as substrate, IC50: 0.0023 mM with 4-hydroxyestradiol as substrate
0.004
(-)-epigallocatechin-3-gallate-4''-O-glucuronide
-
IC50: 0.0025 mM with 2-hydroxyestradiol as substrate, IC50: 0.004 mM with 4-hydroxyestradiol as substrate
0.0006
(-)-epigallocatechin-3-gallate-7-O-glucuronide
-
IC50: 600 nM with 2-hydroxyestradiol as substrate
0.0008
(-)-epigallocatechin-3-gallate-7-O-glucuronide
-
IC50: 800 nM with 4-hydroxyestradiol as substrate
0.00004 - 0.00007
(-)-epigallocatechin-3-O-gallate
-
IC50: 0.04-0.07 microM for the O-methylation of 2-hydroxyestradiol
0.00007
(-)-epigallocatechin-3-O-gallate
-
O-methylation of 2-hydroxyestradiol
0.00037 - 0.00046
(-)-epigallocatechin-3-O-gallate
-
IC50: 0.37-0.46 microM for O-methylation of 4-hydroxyestradiol
0.00054
(-)-epigallocatechin-3-O-gallate
-
O-methylation of 4-hydroxyestradiol
0.0012
(-)-epigallocatechin-3-O-gallate
-
O-methylation of 2-hydroxyestradiol; O-methylation of 4-hydroxyestradiol
0.0015
(-)-epigallocatechin-3-O-gallate
-
O-methylation of 2-hydroxyestradiol
0.0017
(-)-epigallocatechin-3-O-gallate
-
O-methylation of 4-hydroxyestradiol
0.08
(-)epicatechin
-
IC50: 0.06 mM with 2-hydroxyestradiol as substrate, IC50: 0.08 mM with 4-hydroxyestradiol as substrate
0.0316
(2E)-4,7-anhydro-1,2,3-trideoxy-1-(2,3-dihydroxy-5-nitrobenzamido)-L-ribo-hept-2-enitol
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.029
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,5-dihydroxybenzoate)
-
70-79% inhibition at 0.025-0.05 mM
0.3
1,2-dihydroxy-4-[2-(methylamino)butyl]benzene
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.0209
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-4-(trifluoromethyl)-1H-imidazole
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0628
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]benzo[d]imidazole
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.336
1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]pyridin-4(1H)-one
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.2
3,4-dihydroxymethamphetamine
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.00004418
3,5-dinitrocatechol
-
pH 7.4, 37C
0.00015
4'-4''-di-O-methyl-epigallocatechin-3-gallate
-
IC50: 0.00015 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate, competitive with respect S-adenyosylmethionine, noncompetitive with respect to catechol
0.001368
4'-fluoro-4,5-dihydroxy-biphenyl-3-carboxylic acid [(E)-3-[(2S,4R,5R)-4-hydroxy-5-(6-methyl-purin-9-yl)-tetrahydro-furan-2-yl]-allyl]-amide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.001858
4'-fluoro-4,5-dihydroxy-biphenyl-3-carboxylic acid [(E)-3-[(2S,4R,5R)-4-hydroxy-5-(6-methylamino-purin-9-yl)-tetrahydro-furan-2-yl]-allyl]-amide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.04
4'-O-methyl-(-)-epigallocatechin
-
IC50: 0.032 mM with 2-hydroxyestradiol as substrate, IC50: 0.04 mM with 4-hydroxyestradiol as substrate
0.0001
4'-O-methyl-epigallocatechin-3-gallate
-
IC50: 0.0001 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
0.0108
5-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-5H-imidazo[4,5-c]pyridine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0107
5-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]-5H-pyrrolo[3,2-c]pyridine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000006
6-methyl-9-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]purine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000011
9-[(5E)-3,5,6,7-tetradeoxy-3-fluoro-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-xylo-hept-5-enofuranosyl]-N6-methyladenine
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000025
9-[(5E)-3,5,6,7-tetradeoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-3-methyl-beta-D-xylo-hept-5-enofuranosyl]-N6-propyladenine
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000155
9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]purine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.00164
catechin
-
IC50: 0.00164 mM
0.005 - 0.007
catechin
-
IC50: 14-17 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.005-0.007 mM for O-methylation of 4-hydroxyestradiol
0.0066
catechin
-
O-methylation of 4-hydroxyestradiol
0.008
catechin
-
O-methylation of 4-hydroxyestradiol
0.012
catechin
-
O-methylation of 4-hydroxyestradiol
0.0153
catechin
-
O-methylation of 2-hydroxyestradiol
0.016
catechin
-
O-methylation of 2-hydroxyestradiol
0.019
catechin
-
O-methylation of 2-hydroxyestradiol
0.00196
epicatechin
-
IC50: 0.00196 mM
0.01 - 0.018
epicatechin
-
IC50: 44-65 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.01-0.018 mM for O-methylation of 4-hydroxyestradiol
0.015
epicatechin
-
O-methylation of 4-hydroxyestradiol
0.019
epicatechin
-
O-methylation of 4-hydroxyestradiol
0.04
epicatechin
-
O-methylation of 2-hydroxyestradiol
0.0532
epicatechin
-
O-methylation of 2-hydroxyestradiol
0.062
epicatechin
-
O-methylation of 2-hydroxyestradiol
0.068
epicatechin
-
O-methylation of 4-hydroxyestradiol
0.006
epigallocatechin
-
O-methylation of 4-hydroxyestradiol
0.015
epigallocatechin
-
O-methylation of 2-hydroxyestradiol
0.02
epigallocatechin
-
O-methylation of 4-hydroxyestradiol
0.022
epigallocatechin
-
O-methylation of 4-hydroxyestradiol
0.039
epigallocatechin
-
O-methylation of 2-hydroxyestradiol
0.048
epigallocatechin
-
O-methylation of 2-hydroxyestradiol
0.0021
fisetin
-
O-methylation of 4-hydroxyestradiol
0.0026 - 0.0042
fisetin
-
IC50: 0.0026-0.0042 mM for O-methylation of 4-hydroxyestradiol
0.0032
fisetin
-
O-methylation of 4-hydroxyestradiol
0.0033 - 0.0045
fisetin
-
IC50: 0.0033-0.0045 mM for the O-methylation of 2-hydroxyestradiol
0.0035
fisetin
-
O-methylation of 2-hydroxyestradiol
0.0043
fisetin
-
O-methylation of 2-hydroxyestradiol
0.00549
flavone
-
IC50: 0.00549 mM
0.00457
Harmaline
-
pH 7.4, 37C
0.01319
harmalol
-
pH 7.4, 37C
0.002
N-(2-[2-[(2R,3S,4R,5R)-5-(6-amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-ethoxy]-ethyl)-2,3-dihydroxy-5-nitro-benzamide
-
IC50: 0.002 mM
0.0468
N-ethyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-imidazole-4-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.1
N-ethyl-3,4-dihydroxyamphetamine
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.0703
N-methyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-1,2,4-triazole-3-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.0895
N-methyl-1-[(5E)-5,6,7-trideoxy-7-[5-(4-fluorophenyl)-2,3-dihydroxybenzamido]-beta-D-ribo-hept-5-enofuranosyl]-1H-imidazole-4-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000011
N-[(2E)-3-[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(methylamino)-9H-purin-9-yl]tetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000026
N-[(2E)-3-[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(propylamino)-9H-purin-9-yl]tetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000009
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000009
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000031
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000035
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000236
N-[(2E)-3-[(2R,3S,4R,5R)-5-(6-ethyl-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000082
N-[(2E)-3-[(2R,3S,4R,5R)-5-[6-(cyclopropylamino)-9H-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000043
N-[(2E)-3-[(2R,3S,4R,5R)-5-[6-(ethylamino)-9H-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-4'-fluoro-4,5-dihydroxybiphenyl-3-carboxamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.028
N-[(2E)-3-[(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-3-hydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.00004
N-[(2E)-3-[(2S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-2-yl]prop-2-en-1-yl]-2,3-dihydroxy-5-nitrobenzamide
P22734
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000009
N-[(E)-4-[(2R,3S,4R,5R)-5-(6-Amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-but-2-enyl]-2,3-dihydroxy-5-nitro-benzamide
-
IC50: 9 nM
0.00006
N-[2-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]ethyl]-2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 60 nM
0.0002
N-[3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]propyl]2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 200 nM
0.005
N-[4-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]butyl]-2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 0.005 mM
0.09
N-[[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyl]-2,3-dihydroxy-5-nitrobenzene-1-carboxamide
-
IC50: 0.09 mM, very potent bisubstrate inhibitor
0.000032
N6-methyl-9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-beta-D-ribo-hept-5-enofuranosyl]adenine
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.000596
pyridin-4-yl (5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-1-thio-beta-D-ribo-hept-5-enofuranoside
-
liver homogenate, substrate benzene-1,2-diol, pH 7.6, 37C
0.00048
quercetin
-
IC50: 0.00048 mM
0.0005 - 0.0012
quercetin
-
IC50: 0.0009-0.0015 mM for the O-methylation of 2-hydroxyestradiol, IC50: 0.0005-0.0012 mM for O-methylation of 4-hydroxyestradiol
0.0009
quercetin
-
O-methylation of 4-hydroxyestradiol
0.0012
quercetin
-
O-methylation of 2-hydroxyestradiol
0.0021
quercetin
-
O-methylation of 4-hydroxyestradiol
0.0022
quercetin
-
O-methylation of 4-hydroxyestradiol
0.0039
quercetin
-
O-methylation of 2-hydroxyestradiol
0.0045
quercetin
-
O-methylation of 2-hydroxyestradiol
0.0085
quercetin
-
IC50: 0.0085 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
0.000005 - 0.000042
Ro 41-0960
-
IC50: 5-42 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00107
-
pH 7.4, 37C
0.092
-
purified recombinant human catechol-O-methyltransferase from an Escherichia coli cell extract
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8 - 8.4
-
leads to maximal formation of 2-methoxyestradiol-17beta
7 - 8
-
methylation of 2-hydroxyestradiol or 4-hydroxyestradiol by MB-COMT; methylation of 2-hydroxyestradiol or 4-hydroxyestradiol by S-COMT
7
-
membrane-bound enzyme
7.1 - 7.4
-
-
7.3 - 8.2
-
-
7.4
-
membrane-bound activity
7.5 - 8.2
-
-
7.6 - 7.8
-
-
7.8
-
soluble enzyme
7.8
-
soluble activity
9.2
-
leads to maximal formation of 2- and 3-monomethyl ether
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8 - 8
-
about 50% of maximum activity at pH 6.8 and pH 8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
42
-
2-hydroxyestradiol-17beta
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
mononuclear cell
Manually annotated by BRENDA team
-
highest activity in hippocampus. In all brain areas membrane-bound enzyme activity is lower than soluble enzyme activity
Manually annotated by BRENDA team
-
postmortem dorsolateral prefrontal cortex tissue predominantly expresses the membrane-bound isoform. Females have lower COMT activity than males
Manually annotated by BRENDA team
-
catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory
Manually annotated by BRENDA team
-
COMT Val158Met polymorphism is related to structural brain differences in healthy adults. Val158 allele homozygotes exhibit significantly smaller temporal lobe and hippocampal volumes, with a trend for smaller amygdala volumes
Manually annotated by BRENDA team
-
genetic variations of COMT can contribute to brain morphological abnormalities described in early phases of schizophrenia. Low-activity allele of catechol-O-methyltransferase is associated with increased lateral ventricles in patients with first episode non-affective psychosis
Manually annotated by BRENDA team
-
membrane-bound COMT activities in the cerebral cortex are significantly reduced in high-salt loaded Dahl salt-sensitive rats compared with normal-salt loaded Dahl salt-sensitive rats
Manually annotated by BRENDA team
-
paranigral lipopolysaccharide infusion to rats results in intense microglial activation around the lesion area followed by a delayed injury in nigrostriatal pathway in 2 weeks. Simultaneously, catechol-O-methyltransferase activity in the substantia nigra is gradually increased up to 213%. Soluble COMT and membrane bound COMT proteins are increased by 255% and 86%, respectively. Increased catechol-O-methyltransferase immunoreactivity is located primarily into the activated microglial cells in the lesion area
Manually annotated by BRENDA team
-
significant contribution of COMT in modulating the dynamics of dopamine overflow in the prefrontal cortex. Evoked dopamine overflow shows that removal of dopamine is twofold slower in the prefrontal cortex of mice lacking COMT than in wild-type mice, indicating that half of the dopamine decline in this brain region results from COMT-mediated enzymatic degradation. Lack of COMT does not influence dopamine overflow/decline in the dorsal striatum
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
-
membrane-bound COMT activities in the cerebral cortex are significantly reduced in high-salt loaded Dahl salt-sensitive rats compared with normal-salt loaded Dahl salt-sensitive rats
Manually annotated by BRENDA team
-
isoform COMT2
Manually annotated by BRENDA team
-
COMT2 is highly expressed in sensory hair cells of the inner ear
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
-
norepinephrine stimulates alpha2-adrenoceptor of the cells to increase the MB-COMT activity, but not the level of MB-COMT mRNA transcription
Manually annotated by BRENDA team
-
high-salt loading significantly suppresses the activities of membrane-bound COMT and increases the urinary norepinephrine level in Dahl salt-sensitive rats
Manually annotated by BRENDA team
-
S-COMT isoforms are highly and preferentially expressed in kidney
Manually annotated by BRENDA team
-
leukocyte exposure to morphine down-regulates catechol-O-methyl transferase and CYP2D6 by approximately 50% compared with control values. Exposure of white blood cells to 0.001 mM S-nitroso-N-acetyl-DL-penicillamine, a nitric oxide donor, reduces the expression of CYP2D6 and COMT. Prior naloxone (0.001 mM) or N-nitro-L-arginine methyl ester (0.1 mM) addition abrogates down-regulating activity of morphine, demonstrating morphine is initiating its actions via stimulating constitutive NO synthase derived NO release via the mu3 opiate receptor splice variant
Manually annotated by BRENDA team
-
S-COMT isoforms are highly expressed in liver, liver displays a very weak expression of L-COMT isoforms
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
-
no effect of sex on COMT activity
Manually annotated by BRENDA team
-
estradiol-treated
Manually annotated by BRENDA team
-
Val158Met polymorphism within COMT and PvuII polymorphism within ESR1, alone or together with physical activity may, at least partly, modulate muscle mass and performance phenotypes in older women. COMT Val158Met polymorphism is associated with muscle mass in that subjects with the LL genotype have significantly larger muscles than heterozygotes. Furthermore, within are observed than within other sedentary subjects or subjects with more active life-style
Manually annotated by BRENDA team
-
levels of staining for the COMT protein in myometrium are highest on day 1 and lowest on days 8 and 13, but high levels returned by days 16 and 19 of pregnancy. Modulation of COMT activity may play a role in the regulation of myometrial contractility and cervical ripening during pregnancy, modulation of COMT activity may play a role in the regulation of myometrial contractility and cervical ripening during pregnancy
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
-
L-COMT is the predominant enzyme form
Manually annotated by BRENDA team
additional information
-
distribution in various tissues
Manually annotated by BRENDA team
additional information
-
both of the L-COMT isoforms are found in all of the tissues examined except the heart, which expresses only the most acidic form, and the kidney, which expresses only the most basic form
Manually annotated by BRENDA team
additional information
-
isoform COMT2 is not expressed in the central nervous system
Manually annotated by BRENDA team
additional information
-
sexual dimorphism and activity of the two COMT isoforms seems to be tissue specific and more prominent in peripheral tissues than in the brain
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
S-COMT, recombinant enzyme
Manually annotated by BRENDA team
-
isoform S-COMT
Manually annotated by BRENDA team
-
the majority of COMT dopamine-methylating activity is found to be present in the cytosol
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
exists in a soluble cytosolic and in a particulate membrane-bound form
Manually annotated by BRENDA team
-
bound to, MB-COMT
Manually annotated by BRENDA team
-
bound to.In all brain areas membrane-bound enzyme activity is lower than soluble enzyme activity
Manually annotated by BRENDA team
-
membrane-bound enzyme form MB-COMT
Manually annotated by BRENDA team
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT). MB-COMT is an integral membrane protein with the catalytic portion of the enzyme oriented toward the cytoplasmic side of the membrane
Manually annotated by BRENDA team
-
isoform mbCOMT
Manually annotated by BRENDA team
-
S-COMT, recombinant enzyme
Manually annotated by BRENDA team
-
exists in a soluble cytosolic and in a particulate membrane-bound form
-
Manually annotated by BRENDA team
-
in all brain areas membrane-bound enzyme activity is lower than soluble enzyme activity
-
Manually annotated by BRENDA team
-
soluble enzyme form S-COMT
-
Manually annotated by BRENDA team
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
-
Manually annotated by BRENDA team
-
isoform S-COMT
-
Manually annotated by BRENDA team
-
isoform sCOMT
-
Manually annotated by BRENDA team
-
isoform mbCOMT
-
Manually annotated by BRENDA team
additional information
-
-
-
Manually annotated by BRENDA team
additional information
-
MB-COMT, recombinant enzyme, not: plasma membrane
-
Manually annotated by BRENDA team
additional information
-
S-COMT highly expressed in liver and kidney, MB-COMT in brain
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
-
gel filtration
441515
23000
-
gel filtration
441510
23000
-
gel filtration
441513
23000
-
gel filtration
441514
23000
-
gel filtration
441529
24000
-
COMT I, gel filtration, sedimentation data
441508
24000
-
S-COMT, SDS-PAGE
441541
24000
-
isoform S-COMT, SDS-PAGE
702121
24000
-
short catechol-O-methyltransferase transcript of S-COMT in the liver, SDS-PAGE
702948
24300
-
S-COMT
686194
24890
-
calculated from amino acid sequence; ESI Q-pole mass spectrometry
705404
25000 - 26000
-
gel filtration, SDS-PAGE
441519
25000
-
gel filtration
441527
25000
-
isoform S-COMT, SDS-PAGE
703772
27500
-
-
441534
28000
-
MB-COMT, SDS-PAGE
441541
28000
-
isoform L-COMT, SDS-PAGE
702121
28000
-
long catechol-O-methyltransferase transcript of MB-COMT in the liver, SDS-PAGE
702948
30000
-
MB-COMT
686194
32000
-
gel filtration
441526
32000
-
isoform MB-COMT, SDS-PAGE
703772
36000
-
gel filtration
441551
47500
-
COMT II, gel filtration, sedimentation data
441508
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 25000, SDS-PAGE
?
-
x * 23000, SDS-PAGE
?
-
x * 29000, hepatoma cell line G2, SDS-PAGE
?
-
1 * 24000, S-COMT, SDS-PAGE, x * 30000, MB-COMT, SDS-PAGE
?
-
x * 30000 (His-tagged protein), SDS-PAGE
monomer
-
-
monomer
-
1 * 25000, SDS-PAGE
monomer
-
1 * 23000, SDS-PAGE
monomer
-
1 * 23000, SDS-PAGE
monomer
-
1 * 25700, liver, SDS-PAGE
monomer
-
1 * 36000, SDS-PAGE, gel filtration
monomer
-
1 * 24889, ESI Q-pole mass spectrometry, 1 * 24891, calculated from amino acid sequence
monomer
Streptomyces griseus S-COMT
-
1 * 36000, SDS-PAGE, gel filtration
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
S-COMT is a nonglycosylated protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure
-
sitting-drop vapor-diffusion method, crystal structures of the 108V and 108M variants of the soluble form of human COMT bound with S-adenosylmethionine and a substrate analog, 3,5-dinitrocatechol
-
apo and holo forms of rat catechol-O-methyltransferase, hanging drop vapor diffusion method, the apo crystals are grown from 0.2 M (NH4)2SO4, 30% (w/v) PEG8000, the holo form of crystals are grown from 0.2 M (NH4)2SO4, 26% (w/v) PEG8000, 0.2% (v/v) sucrose
-
in complex with 4-phenyl-7,8-dihydroxycoumarin, hanging drop vapor diffusion method, using 0.2 M (NH4)2SO4, 0.1 M Tris pH 7.5, 30% (w/v) PEG8000
-
sitting drop vapour diffusion method
P22734
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
2 h, inactivation
441507
37
-
MB-COMT protein is quite stable at 37C; S-COMT protein is quite stable at 37C
686075
50 - 60
-
wild type soluble COMT loses most of the native helical structure in a sharp melting transition between 50 and 60C
702413
additional information
-
variants 108M and 108V differ in their thermal stability with COMT losing catalytic activity more rapidly
659347
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine significantly stabilizes the secondary structures of the wild type enzyme
-
complete loss of activity on freezing solid
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 100 mM potassium phosphate, pH 8.0, 1 mM EDTA, 1 mM 2-mercaptoethanol, 5 mM dithiothreitol, 40% v/v glycerol, 1 mg/ml bovine serum albumin, stable for 4 months
-
-10C, 3 months, stable
-
-20C, or -60C, 50 mM Tris-HCl, pH 7.5, 20 mM 2-mercaptoethanol, 20% v/v glycerol, 60-80% of activity retained after 6 months
-
-4C, stable for several weeks
-
-5C, 20% v/v glycerol, stable for 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
immobilized metal ion affinity chromatography
-
overview on purification of native and recombinant protein
-
purification of recombinant human soluble COMT using hydrophobic interaction chromatography, as the main isolation method, from an Escherichia coli culture broth
-
TALON metal affinity resin column chromatography, Superdex 75 gel filtration
-
affinity chromatography
-
GST 4B Sepharose resin column chromatography, Super Q-5PW column chromatography, and Superdex 75 gel filtration
-
GST Sepharose resin column chromatography, GSTrap column chromatography, Super Q-5PW column chromatography, and Superdex 75 gel filtration
-
microsomal
-
overview on purification of native and recombinant protein
-
recombinant enzyme
-
soluble and microsomal enzyme
-
soluble form
-
commercial preparation
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-tagged protein expressed in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression of the human soluble and membrane-bound COMTs (S-COMT and MBCOMT, respectively) in Escherichia coli. The two recombinant human COMTs are functionally active, with catalytic and kinetic properties nearly identical to that of crude or purified enzymes prepared from human tissues or cells
-
generation of transgenic mice overexpressing a human COMT-Val polymorphism
-
S-COMT and MB-COMT are encoded by a single gene with two different sites of transcription initiation, overview on genetic polymorphism
-
expressed in HEK-293 cells
-
expressed in Escherichia coli BL21 Codon Plus (DE3) cells
-
gene expressed in Escherichia coli
-
S-COMT and MB-COMT are encoded by a single gene with two different sites of transcription initiation, overview on genetic polymorphism
-
soluble part from M44 to S264 expressed in Escherichia coli W3110[pREP4]
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
4-(tert-octyl)phenol, benzyl butyl phthalate, diisononyl phthalate, dibutyl phthalate, and dioctyl phthalate inhibit S-COMT protein expression in MCF-7 cells at 72 h, the inhibitory effect is abolished in the presence of the anti-estrogen ICI182780
-
COMT protein expression is down-regulated in the midsecretory phase of the menstrual cycyle, progesterone down-regulates soluble COMT protein expression
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COMT protein expression levels are statistically significantly reduced by both, catechol and phenolic metabolites of polychlorinated biphenyls: 2,5-dichlorobiphenyl, 2',5'-dichlorobiphenyl-2-ol, 2',5'-dichlorobiphenyl-2,3-diol, 2',5'-dichlorobiphenyl-3,4-diol, 2',5'-dichlorobiphenyl-4-ol, 2',4'-dichlorobiphenyl-4-ol, 2',4',6'-trichlorobiphenyl-4-ol, 2',4',6'-trichlorobiphenyl-3,4-diol, and 2',4',5'-trichlorobiphenyl-3,4-diol. The changes in COMT expression are abolished in the presence of the anti-estrogen ICI182780
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COMT protein expression is up-regulated in the proliferative phase of the menstrual cycyle, estrogen up-regulates soluble COMT protein expression
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there are no effects of gonadectomy itself on COMT-s activity, there are significant effects of hormone replacement (supplementation with testosterone propionate or with estradiol for 28 days) but not gonadectomy on the soluble but not the membrane-bound isoform of catechol-O-methyltransferase in both striatum and brain cortex
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C69S
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mutation makes variant 108V and 108M more sensitive to oxidation
C95S
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mutation increases the activity measured in absence of dithiothreitol in both the 108V and the 108M variant
V108M
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the mutation decreases the structural stability of catechol O-methyltransferase, the mutant loses enzymatic activity more rapidly than the wild type enzyme at physiological temperature, the midpoint of the thermal transition of V108M is 5-7C lower than that of wild type enzyme, and the free energy of unfolding at 25C is smaller by about 0.4 kcal/mol, the mutant also iss more prone to aggregation or partial unfolding to a form with an increased radius of hydration at 37C. The mutation is associated with increased risk of breast cancer and several neuropsychiatric disorders,
V108M
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the mutation is associated with an increased risk for breast cancer
V158M
A3F6Y9
the mutation affects directly COMT enzyme activity, the COMT polymorphism is unconnected to cold pain
M91I/Y95C
P22734
active site humanized enzyme
L16P
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missense mutation
additional information
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genetic variation in the catechol-O-methyltansferase enzyme is associated independently with morphine-related central side effects in cancer patients, such as drowsiness, confusion, and hallucinations. Single nucleotide polymorphisms in intron 1 are associated significantly with these central side effects, the most significant is at position 24873G
Y71X
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the mutation is predicted to truncate the protein before the catalytic domain likely affecting methyltransferase activity
additional information
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the add mutation substantially diminishes COMT1 methyltransferase activity toward norepinephrine
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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high-performance liquid chromatography determination of methionine adenosyltransferase activity using catechol-O-methyltransferase-coupled fluorometric detection, a nonradioactive, sensitive, rapid, and specific method for the determination of methionine adenosyltransferase activity
analysis
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design of electrochemical biosensor systems for the detection of specific DNA sequences in PCR-amplified nucleic acids related to the catechol-O-methyltransferase Val108/158Met polymorphism based on intrinsic guanine signal
medicine
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COMT activity may alter neurotransmitter deposition and transport
medicine
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comparison of COMT isoforms and implications for breast cancer risk
medicine
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genetic variation in COMT gene (MIM 116790) is associated with altered prefrontal cortex function and higher risk for schizophrenia. A common single-nucleotide polymorphism within COMT, Val158Met, significantly affects protein abundance and enzyme activity but not mRNA expression levels. Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function
medicine
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inhibition of catechol-O-methyltransferase is an important approach in the treatment of Parkinson's disease
medicine
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a functional COMT polymorphism (Val158Met) predicts performance in tasks of prefrontal executive function and the neurophysiological response measured with electroencephalography and functional magnetic resonance imaging in tasks assessing working memory. In fact, individuals with the Val/Val genotype, which encodes for the high-activity enzyme resulting in lower dopamine concentrations in the prefrontal cortex, perform less well and are less efficient physiologically than Met/Met individuals
medicine
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association between the COMT Val158Met polymorphism and anger-related personality traits in suicide attempters. COMT Val158Met shows a strong effect on Trait Anger and Anger Control scores in female suicide attempters and a weaker effect on the Trait Anger score in violent suicide attempters of both genders
medicine
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association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder. 62.5% of the patients showing a good response to methylphenidate treatment have the Val/Val genotype, 41.7% and 11.7% of the patients showing a poor response to methylphenidate treatment as assessed by their teachers have the Val/Met and Met/Met genotypes
medicine
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COMT activity and increased formation of depurinating adducts can be critical factors leading to initiation of breast cancer
medicine
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COMT genotype directly influences cognitive phenotype in Parkinsons disease through altering activation in a frontoparietal executive neural network. COMT genotype has differing effects on prefrontal function according to underlying dopaminergic state
medicine
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COMT Val158Met polymorphism modulates the association between physical activity, areal bone mineral density, and trabecular volumetric bone mineral density, suggesting that this polymorphism is of importance for bone mineral density in subjects with a low level of physical activity
medicine
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in boys there appeared to be a population shift toward higher verbal IQ with increasing Met allele dose (Val108/158Met polymorphism). The effects on IQ are significantly greater in pubertal than in prepubertal boys. In girls, there are no significant effects of genotype on cognition
medicine
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L-dopa treatment is an acquired cause of hyperhomocysteinemia. The mechanism underlying L-dopa-related hyperhomocysteinemia is the O-methylation of the drug catalyzed by the enzyme catechol-O-methyltransferase. L-Dopa is the gold standard in the symptomatic management of Parkinsons disease, but its long-term treatment is complicated by the elevation in plasma homocysteine concentrations, due to the O-methylation by COMT
medicine
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significant association between the COMT Val158Met polymorphism and specific clinical features related to the onset of psychosis in a large and representative sample of first episode patients. These results suggest that COMT genotype may have a role in the pathogenesis of psychotic disorders and therefore takes part in the etiological model for schizophrenia and other psychoses
medicine
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single nucleotide polymorphisms rs6269, rs4633, rs4818, and rs4680, tagging the common putative functional COMT haplotypes, are genotyped in 435 adult subjects with a clinical diagnosis of ADHD and 383 controls and analyzed for association with attention-deficit/hyperactivity disorder and the hyperactivity/impulsivity and in attention dimensions from the Adult ADHD Self-Report Scale. Haplotype analysis reveales that the rs6269 risk allele tags the suggested high COMT-activity haplotype, which is associated with the highest hyperactivity/impulsivity score
medicine
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the COMT Val158Met polymorphism is associated with fracture risk in elderly men, through a mechanism independent of bone mineral density
medicine
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the functional catechol-O-methyltransferase (COMT) Val158Met polymorphism interacts significantly with total Childhood Trauma Questionnaire abuse scores to impact perceived dissociation. The Val/Val genotype is associated with increasing levels of dissociation in participants exposed to higher levels of childhood trauma. The opposite is observed in people with Met/Met genotypes who display decreased dissociation with increasing self-reported childhood trauma. COMT Val158Met polymorphism is involved in mediating the relationship between trauma and psychopathology
medicine
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the present meta-analysis provides tentative support for the COMT Val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect
medicine
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COMT activity has an influence on cell transforming activity and its related genetic effects of catechol estrogens imply that an individual activity of COMT may be one of the etiological factors in endogenous estrogen-induced carcinogenesis
medicine
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therapeutic potential of manipulating COMT activity to alter dopaminergic neurotransmission in the prefrontal cortex
medicine
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catechol-O-methyltransferase activity and protein expression are increased in the substantia nigra after inflammation induced by lipopolysaccharides. These changes in glial and perivascular catechol-O-methyltransferase activity may have clinical relevance for Parkinsons disease drug treatment due to increased metabolism of levodopa in the brain
medicine
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low COMT activity leads to increased pain sensitivity via a beta2/3-adrenergic mechanism. These findings are of considerable clinical importance, suggesting that pain conditions resulting from low COMT activity and/or elevated catecholamine levels can be treated with pharmacological agents that block both beta2- and beta3-adrenergic receptors