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Information on EC 2.1.1.6 - catechol O-methyltransferase and Organism(s) Homo sapiens and UniProt Accession P21964
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2.1.1.6 catechol O-methyltransferaseIUBMB Comments
The mammalian enzyme acts more rapidly on catecholamines such as adrenaline or noradrenaline than on catechols.
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Word Map
- 2.1.1.6
- dopamine
-
val158met
- catechols
- parkinson
-
monoamine
-
dopaminergic
-
schizophrenia
-
prefrontal
- levodopa
- estrogen
- val
-
o-methylation
-
psychiatric
- norepinephrine
- entacapone
- l-dopa
- tolcapone
- serotonin
- noradrenaline
- dyskinesia
-
neurotransmitter
- striatal
-
psycho
-
dopac
- carbidopa
-
verbal
-
3,4-dihydroxyphenylacetic
-
extraneuronal
-
5-httlpr
-
low-activity
-
parkinsonian
-
homovanillic
- normetanephrine
- benserazide
-
antiparkinsonian
- synthesis
-
endophenotype
-
dsm-iv
-
3h-noradrenaline
- 2-methoxyestradiol
- analysis
- tropolone
-
updrs
-
slc6a4
-
dihydroxyphenylacetic
- amantadine
- pargyline
-
oxidase-b
-
phenylethanolamine-n-methyltransferase
- metanephrine
- selegiline
- medicine
-
antisocial
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
catechol-o-methyltransferase, catechol-o-methyl transferase, catechol o-methyltransferase, s-comt, mb-comt, comt1, comt i, comt ii, catechol methyltransferase, ctomt1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
catechol methyltransferase
-
-
-
-
catecholamine O-methyltransferase
-
-
-
-
COMT
COMT I
-
-
-
-
COMT II
-
-
-
-
MB-COMT
methyltransferase, catechol
-
-
-
-
S-COMT
SCOMT
COMT
-
-
MB-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
S-COMT
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
mechanism
-
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
ordered reaction mechanism with S-adenosyl-L-methionine as the leading substrate
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
O-methylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -
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.
CAS REGISTRY NUMBER
COMMENTARY
9012-25-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(-)-epigallocatechin-3-O-gallate + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
poor substrate for methylation
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 1-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 2,3-dihydroxybenzaldehyde
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 2,3-dihydroxynaphthalene
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 2-(1-thienyl)ethyl-3,4-dihydroxybenzylcyano acetate
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxyacetophenone
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxybenzoic acid ethyl ester
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxymandelic acid
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxyphenylacetic acid
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxyphenylglycol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3-fluorocatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3-methoxy-5-bromocatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 3-methoxycatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-chlorocatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-isopropylcatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-methylcatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-nitrocatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-tert-butyl-5-methoxycatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 4-tert-butylcatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 5-hydroxydopamine
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 6-hydroxydopa
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 6-hydroxydopamine
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + adrenaline
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + carbidopa
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + catecholamine
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + chlorogenic acid
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + dihydrexidine
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + dobutamine
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + dopamine
S-adenosyl-L-homocysteine + 3-O-methyldopamine
-
-
-
?
S-adenosyl-L-methionine + epicatechin
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + epicatechin gallate
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin gallate
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + ethyl-3,4-dihydroxybenzylcyanoacetate
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + gallic acid
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + methyl gallate
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + noradrenaline
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + pyrogallol
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + rosmarinic acid
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + salsoline
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + salsoline-1-carboxylic acid
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + tetrachlorocatechol
S-adenosyl-L-homocysteine + ?
-
-
-
?
(+)-catechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
3'-O-methyl derivatives are consistently the main metabolites, 3'-O-methyl derivatives are consistently the main metabolites, meta/para ratio of the metabolites is approximately 25:1
-
?
(+)-epicatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
(-)-epigallocatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
(-)-epigallocatechin-3-O-gallate + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
(R)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene + S-adenosyl-L-methionine
?
-
-
-
-
?
(S)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene + S-adenosyl-L-methionine
?
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
2-hydroxyestradiol 3-methyl ether + S-adenosyl-L-homocysteine
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
2-methoxyestradiol + S-adenosyl-L-homocysteine
-
-
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 2-methoxyestradiol + 2-hydroxy-3-methoxyestradiol
-
-
-
-
?
2-hydroxyestradiol-17beta + S-adenosyl-L-methionine
2-methoxyestradiol-17beta + 2-hydroxyestradiol-17beta methyl ether + S-adenosyl-L-homocysteine
-
-
-
?
3,4-dihydroxybenzoic acid + S-adenosyl-L-methionine
4-hydroxy-3-methoxybenzoic acid + S-adenosyl-L-homocysteine
-
-
the meta/para ratio of the metabolites is approximately 4.5
-
?
3,4-dihydroxybenzoic acid + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
3,5-dinitrocatechol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
3-hydroxytyramine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-methoxytyramine
-
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
(17beta)-estra-1(10),2,4-triene-3,4,17-triol + S-adenosyl-L-homocysteine + ?
-
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
-
-
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-O-methyldopamine
-
-
-
-
?
L-dopa + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + 3-O-methyl-L-dopa
-
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + normetanephrine
-
-
-
-
?
procyanidin dimer B1 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites
-
?
procyanidin dimer B2 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites
-
?
procyanidin dimer B3 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites
-
?
procyanidin dimer B4 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites
-
?
procyanidin dimer B5 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites
-
?
procyanidin dimer B7 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites
-
?
procyanidin trimer C1 + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
flavanyl units of procyanidins are methylated consecutively, leading to monomethylated, dimethylated, and trimethylated C1 metabolites
-
?
S-adenosyl-L-homocysteine + 4''-O-methyl epigallocatechin gallate
S-adenosyl-L-homocysteine + 4',4''-di-O-methyl epigallocatechin gallate
-
-
-
-
?
S-adenosyl-L-methionine + 2-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
S-adenosyl-L-methionine + 3,4-dihydroxy-L-Phe
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
S-adenosyl-L-methionine + 4-hydroxyequilenin
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
S-adenosyl-L-methionine + 4-hydroxyestradiol
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin gallate
S-adenosyl-L-homocysteine + 4''-O-methyl epigallocatechin gallate
-
-
-
-
?
S-adenosyl-L-methionine + epigallocatechin-3-gallate
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
tolcapone + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
inhibitor of isoform MB-COMT, substrate of isoform S-COMT
-
-
?
(-)-epicatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
(-)-epicatechin + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
3'-O-methyl derivatives are consistently the main metabolites, the meta/para ratio of the metabolites is approximately 6:1
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
MB-COMT methylates both 2-hydroxyestradiol and 4-hydroxyestradiol at comparable rates
-
-
?
2-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
S-COMT methylates 2-hydroxyestradiol roughly twice as fast as it methylates 4-hydroxyestradiol
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
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 + ?
-
MB-COMT methylates both 2-hydroxyestradiol and 4-hydroxyestradiol at comparable rates
-
-
?
4-hydroxyestradiol + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
S-COMT methylates 2-hydroxyestradiol roughly twice as fast as it methylates 4-hydroxyestradiol
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
membrane-bound enzyme form MB-COMT
-
-
?
dopamine + S-adenosyl-L-methionine
S-adenosyl-L-homocysteine + ?
-
soluble enzyme form S-COMT
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
-
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
-
-
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
-
membrane-bound enzyme form MB-COMT
-
-
?
epinephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
-
soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + catechin
S-adenosyl-L-homocysteine + ?
-
membrane-bound enzyme form MB-COMT
-
-
?
S-adenosyl-L-methionine + catechin
S-adenosyl-L-homocysteine + ?
-
soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + epicatechin
S-adenosyl-L-homocysteine + ?
-
membrane-bound enzyme form MB-COMT
-
-
?
S-adenosyl-L-methionine + epicatechin
S-adenosyl-L-homocysteine + ?
-
soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + fisetin
S-adenosyl-L-homocysteine + ?
-
membrane-bound enzyme form MB-COMT
-
-
?
S-adenosyl-L-methionine + fisetin
S-adenosyl-L-homocysteine + ?
-
soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
-
membrane-bound enzyme form MB-COMT
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + ?
-
soluble enzyme form S-COMT
-
-
?
S-adenosyl-L-methionine + quercetin
S-adenosyl-L-homocysteine + ?
-
membrane-bound enzyme form MB-COMT
-
-
?
S-adenosyl-L-methionine + quercetin
S-adenosyl-L-homocysteine + ?
-
soluble enzyme form S-COMT
-
-
?
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism
-
-
?
additional information
?
-
-
degree and position of methylation depend clearly on the three-dimensional structure of the entire substrate molecule
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-hydroxyestradiol + S-adenosyl-L-methionine
(17beta)-estra-1(10),2,4-triene-3,4,17-triol + S-adenosyl-L-homocysteine + ?
-
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 + ?
-
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
-
-
?
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
additional information
-
activity of the enzyme is strongly influenced by the nature of the buffer
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxy-2-methylpropyl)pyridin-4(1H)-one
-
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-[hydroxy(phenyl)methyl]pyridin-4(1H)-one
-
3-hydroxy-4'-phenyl-4H-[1,2'-bipyridin]-4-one
potent inhibitor with sufficient in vivo exposure to significantly affect the dopamine metabolites homovanillic acid and dihydroxyphenylacetic acid
5-(cyclopentylsulfonyl)-7-fluoroquinolin-8-ol
compound displays good pharmacokinetics in rats. pIC50 value 8.7 for membrane-bound form, 5.6 for soluble form
7-chloro-5-((4-fluorophenyl)sulfonyl)quinolin-8-ol
compound exhibits very low clearance and long half-life in rat pharmacokinetics studies. pIC50 value 6.7 for membrane-bound form, below 5 for soluble form
7-chloro-5-(cyclopentylsulfonyl)quinolin-8-ol
compound exhibits very low clearance and long half-life in rat pharmacokinetics studies. pIC50 value 7.7 for membrane-bound form, below 5 for soluble form
7-chloro-5-(pyrrolidin-1-ylsulfonyl)quinolin-8-ol
compound exhibits very low clearance and long half-life in rat pharmacokinetics studies . pIC50 value 8.0 for membrane-bound form, 5.5 for soluble form
7-fluoro-5-(pyrrolidin-1-ylsulfonyl)quinolin-8-ol
compound displays good pharmacokinetics in rats. pIC50 value 8.4 for membrane-bound form, 5.8 for soluble form
8-O-methyldaphnetin
0.1 mM, about 20% residual activity. 8-O-methyldaphnetin has no effect on Km but decreases Vmax
lactoferrin
bovine lactoferrin binds to and inhibits COMT using its N-terminal region. A fragment of the lactoferrin N-terminal residues 6-50, with two pairs of disulfide bonds, shows higher inhibitory activity than intact lactoferrin. Lactoferrin does not compete with S-adenosylmethionine. COMT activity in the cell extracts form Caco-2 and HepG2 cells is inhibited by lactoferrin and the N-terminal fragment
-
(-)-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-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
(-)epicatechin
-
IC50: 0.06 mM with 2-hydroxyestradiol as substrate, IC50: 0.08 mM with 4-hydroxyestradiol as substrate
(2-amino-3-methylbutanoyloxy)methyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
(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[3,4,5-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-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one
-
-
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'-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-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
5-hydroxy-1-[3-(isoquinolin-4-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one
-
-
butyryloxymethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
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
epigallocatechin-3-gallate
-
inhibition in vitro. Supplementation with a high dose does not impair the activity of COMT
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
isobutyryloxymethyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
-
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-[(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
(-)-epigallocatechin-3-gallate
-
IC50: 70 nM with 2-hydroxyestradiol as substrate, IC50: 80 nM with 4-hydroxyestradiol as substrate, mixed inhibitor
(-)-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
caffeic acid
-
COMT from liver, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
caffeic acid
-
COMT from liver, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
caffeic acid
-
COMT from placenta, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
caffeic acid
-
COMT from placenta, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
caffeic acid phenethyl ester
-
COMT from liver, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
caffeic acid phenethyl ester
-
COMT from liver, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
catechin
-
IC50: 14-17 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.005-0.007 mM for O-methylation of 4-hydroxyestradiol
chlorogenic acid
-
COMT from liver, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
chlorogenic acid
-
COMT from liver, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
chlorogenic acid
-
COMT from placenta, using 2-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
chlorogenic acid
-
COMT from placenta, using 4-hydroxyestradiol as substrate, in Tris-HCl buffer (10 mM, pH 7.4), at 37°C
epicatechin
-
IC50: 44-65 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.01-0.018 mM for O-methylation of 4-hydroxyestradiol
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
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
-
IC50: 0.0085 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
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
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
tolcapone
-
tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation in HaCat cells. High concentrations of tolcapone reduce melanin levels in melanoma cells parallel to reduced cell numbers
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
-
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
-
(-)-epigallocatechin is not active even at a concentration of 0.05 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
activity of the enzyme is strongly influenced by the nature of the buffer
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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)
0.001
2-hydroxyestradiol
-
COMT from placenta, in Tris-HCl buffer (10mM, pH 7.4), at 37°C
0.0035
4-hydroxyestradiol
-
COMT from placenta, in Tris-HCl buffer (10mM, pH 7.4), at 37°C
0.01
catechol
-
recombinant enzyme expressed in Escherichia coli, membrane-bound enzyme form
0.108
catechol
-
recombinant enzyme expressed in Escherichia coli, soluble enzyme form
0.015
dopamine
-
recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form
0.266
levodopa
-
recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form
0.024
norepinephrine
-
recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form
0.369
norepinephrine
-
recombinant enzyme expressed in Sf9 cells, soluble enzyme form
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.0000016
(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
0.000001
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
0.0000102
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
0.000017
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
0.0000092
propyl-3-chloro-5,6-dihydroxy-7-nitrobenzo[b]thiophene-2-carboxylate
-
pH not specified in the publication, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00016
1-(4-butylphenyl)-5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.00018 - 0.0019
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxy-2-methylpropyl)pyridin-4(1H)-one
0.00014
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.000088 - 0.0013
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-[hydroxy(phenyl)methyl]pyridin-4(1H)-one
0.00014
1-([1,1'-biphenyl]-4-yl)-5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.000084
13-hydroxy-36-(trifluoromethyl)-14H-[11,22:24,32-terpyridin]-14-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0000495
4'-(1-benzyl-1H-pyrazol-4-yl)-3-hydroxy-4H-[1,2'-bipyridin]-4-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.000035
4'-(3,4-dichlorophenyl)-3-hydroxy-4H-[1,2'-bipyridin]-4-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.00086
5-hydroxy-2-(thiophen-2-yl)pyrimidin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0004
9-hydroxypyrido[2,1-c][1,4]benzothiazin-8(6H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0003
(-)-epicatechin-3-gallate
Homo sapiens
-
IC50: 0.0002 mM with 2-hydroxyestradiol as substrate, IC50: 0.0003 mM with 4-hydroxyestradiol as substrate
0.0025
(-)-epigallocatechin-3-gallate-3''-O-glucuronide
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
IC50: 0.0025 mM with 2-hydroxyestradiol as substrate, IC50: 0.004 mM with 4-hydroxyestradiol as substrate
0.08
(-)epicatechin
Homo sapiens
-
IC50: 0.06 mM with 2-hydroxyestradiol as substrate, IC50: 0.08 mM with 4-hydroxyestradiol as substrate
0.029
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,5-dihydroxybenzoate)
Homo sapiens
-
70-79% inhibition at 0.025-0.05 mM
0.3
1,2-dihydroxy-4-[2-(methylamino)butyl]benzene
Homo sapiens
-
isoform sCOMT, in phosphate buffer (pH 7.4)
0.0000449 - 0.000857
1-[1-(2-chlorobenzyl)-1H-benzimidazol-4-yl]-3-hydroxypyridin-4(1H)-one
0.000039 - 0.000226
1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one
0.00015
4'-4''-di-O-methyl-epigallocatechin-3-gallate
Homo sapiens
-
IC50: 0.00015 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate, competitive with respect S-adenyosylmethionine, noncompetitive with respect to catechol
0.04
4'-O-methyl-(-)-epigallocatechin
Homo sapiens
-
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
Homo sapiens
-
IC50: 0.0001 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
0.000063 - 0.000175
5-hydroxy-1-[3-(isoquinolin-4-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one
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
Homo sapiens
-
IC50: 0.002 mM
0.1
N-ethyl-3,4-dihydroxyamphetamine
Homo sapiens
-
isoform sCOMT, in phosphate buffer (pH 7.4)
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
IC50: 0.09 mM, very potent bisubstrate inhibitor
0.00007
(-)-epigallocatechin-3-O-gallate
Homo sapiens
O-methylation of 2-hydroxyestradiol
0.00054
(-)-epigallocatechin-3-O-gallate
Homo sapiens
O-methylation of 4-hydroxyestradiol
0.000047
1-([1,1'-biphenyl]-3-yl)-3-hydroxypyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0011
1-([1,1'-biphenyl]-3-yl)-3-hydroxypyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.00018
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxy-2-methylpropyl)pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0019
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxy-2-methylpropyl)pyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.00057
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxybutyl)pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.001
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxybutyl)pyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.000099
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0014
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.000053
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-methylpyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0021
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-methylpyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.00087
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-phenylpyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0025
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-phenylpyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.000088
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-[hydroxy(phenyl)methyl]pyridin-4(1H)-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.0013
1-([1,1'-biphenyl]-3-yl)-5-hydroxy-2-[hydroxy(phenyl)methyl]pyridin-4(1H)-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.00004
3-hydroxy-4'-phenyl-4H-[1,2'-bipyridin]-4-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.00302
3-hydroxy-4'-phenyl-4H-[1,2'-bipyridin]-4-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.000055
4'-fluoro-3-hydroxy-5'-phenyl-4H-[1,3'-bipyridin]-4-one
Homo sapiens
membrane-bound isoform, pH not specified in the publication, temperature not specified in the publication
0.000946
4'-fluoro-3-hydroxy-5'-phenyl-4H-[1,3'-bipyridin]-4-one
Homo sapiens
soluble isoform, pH not specified in the publication, temperature not specified in the publication
0.044
(-)-epigallocatechin
Homo sapiens
-
IC50: 0.044 mM with 2-hydroxyestradiol as substrate,
0.00007
(-)-epigallocatechin-3-gallate
Homo sapiens
-
IC50: 70 nM with 2-hydroxyestradiol as substrate
0.00008
(-)-epigallocatechin-3-gallate
Homo sapiens
-
IC50: 80 nM with 4-hydroxyestradiol as substrate, mixed inhibitor
0.0006
(-)-epigallocatechin-3-gallate-7-O-glucuronide
Homo sapiens
-
IC50: 600 nM with 2-hydroxyestradiol as substrate
0.0008
(-)-epigallocatechin-3-gallate-7-O-glucuronide
Homo sapiens
-
IC50: 800 nM with 4-hydroxyestradiol as substrate
0.00004 - 0.00007
(-)-epigallocatechin-3-O-gallate
Homo sapiens
-
IC50: 0.04-0.07 microM for the O-methylation of 2-hydroxyestradiol
0.00037 - 0.00046
(-)-epigallocatechin-3-O-gallate
Homo sapiens
-
IC50: 0.37-0.46 microM for O-methylation of 4-hydroxyestradiol
0.0000449
1-[1-(2-chlorobenzyl)-1H-benzimidazol-4-yl]-3-hydroxypyridin-4(1H)-one
Homo sapiens
-
isoform MB-COMT, pH 7.4, 37°C
0.000857
1-[1-(2-chlorobenzyl)-1H-benzimidazol-4-yl]-3-hydroxypyridin-4(1H)-one
Homo sapiens
-
isoform S-COMT, pH 7.4, 37°C
0.000039
1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one
Homo sapiens
-
isoform MB-COMT, pH 7.4, 37°C
0.000226
1-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]-5-hydroxy-2-(1-hydroxyethyl)pyridin-4(1H)-one
Homo sapiens
-
isoform S-COMT, pH 7.4, 37°C
0.000063
5-hydroxy-1-[3-(isoquinolin-4-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one
Homo sapiens
-
isoform MB-COMT, pH 7.4, 37°C
0.000175
5-hydroxy-1-[3-(isoquinolin-4-yl)phenyl]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one
Homo sapiens
-
isoform S-COMT, pH 7.4, 37°C
0.005 - 0.007
catechin
Homo sapiens
-
IC50: 14-17 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.005-0.007 mM for O-methylation of 4-hydroxyestradiol
0.01 - 0.018
epicatechin
Homo sapiens
-
IC50: 44-65 nM for the O-methylation of 2-hydroxyestradiol, IC50: 0.01-0.018 mM for O-methylation of 4-hydroxyestradiol
0.0026 - 0.0042
fisetin
Homo sapiens
-
IC50: 0.0026-0.0042 mM for O-methylation of 4-hydroxyestradiol
0.0033 - 0.0045
fisetin
Homo sapiens
-
IC50: 0.0033-0.0045 mM for the O-methylation of 2-hydroxyestradiol
0.0005 - 0.0012
quercetin
Homo sapiens
-
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
0.0085
quercetin
Homo sapiens
-
IC50: 0.0085 mM with 2-hydroxyestradiol or 4-hydroxyestradiol as substrate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.092
additional information
0.092
-
purified recombinant human catechol-O-methyltransferase from an Escherichia coli cell extract
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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
-
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
-
-
441507, 441508, 441511, 441512, 441523, 441527, 441538, 657883, 658268, 658520, 658525, 686075, 703190, 705398, 734846
-
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
-
-
-
postmortem dorsolateral prefrontal cortex tissue predominantly expresses the membrane-bound isoform. Females have lower COMT activity than males
-
catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory
-
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
-
norepinephrine stimulates alpha2-adrenoceptor of the cells to increase the MB-COMT activity, but not the level of MB-COMT mRNA transcription
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
the majority of COMT dopamine-methylating activity is found to be present in the cytosol
-
exists in a soluble cytosolic and in a particulate membrane-bound form
-
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
-
exists in a soluble cytosolic and in a particulate membrane-bound form
-
-
two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)
-
additional information
S-COMT highly expressed in liver and kidney, MB-COMT in brain
-
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
metabolism
-
concerted action of cytosolic sulfotransferase SULT1A3 and COMT in dopamine metabolism
physiological function
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
physiological function
-
exposure to catechol enhances hemin-induced hemoglobin accumulation and induces mRNA expression of erythroid-specific genes in K-562 cells. Treatment with catechol causes a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K-562 cells. Knock down of COMT expression significantly reduces the production of guaiacol, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increases. Knockdown of COMT expression also eliminates catechol-enhanced erythroid differentiation of K-562 cells. The pretreatment with S-adenosyl-L-methionine or S-adenosyl-L-homocysteine induces a significant increase in hemin-induced hemoglobin synthesis in K-562 cells and the mRNA expression of erythroid specific genes
physiological function
-
inhibition of catechol O-methyltransferase by inhibitor tropolone results in a decrease of the total amount of sulfated metabolites of dopamine, epinephrine, isoproterenol, and isoetharine. The sequential methylation and sulfation of dopamine, epinephrine, isoproterenol, and isoetharine is mediated by, respectively, the COMT and the cytosolic sulfotransferase SULT1A3
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). COMT_HUMAN
271
1
30037
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25000
30000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
bidentate and monodentate binding modes of substrate catecholamine are close in energy but separated by a 7 kcal/mol free energy barrier. The driving force for monodentate catecholate orientations in classical molecular dynamics simulations is derived from stronger electrostatic stabilization afforded by alternate Mg2+ coordination with strongly charged active site carboxylates. Mixed semi-empirical-classical substrate C-O distances (2.7 A) for the bidentate case are in agreement with COMT X-ray crystal structures, as long as charge transfer between the substrates, Mg2+, and surrounding ligands is permitted. Free energy barriers for methyl transfer from bidentate and monodentate catecholate configurations are comparable at around 21-22 kcal/mol
quantum mechanical/molecular mechanical dynamics analysis of the effect of metal substitution on the rate determining step in the catalytic cycle of COMT, the methyl transfer. In full accord with experimental data, Mg(II) bound to COMT is the most potent of the studied cations and it is closely followed by Fe(II), whereas Fe(III) is unable to promote catalysis. Ca(II) induces a repacking of the protein binding site, leading to a significant increase in the activation barrier and higher energy of reaction. The effect of metal substitution is different for different metals: for Fe(III) it is the electronic effect, for Ca(II) it is the effect of suboptimal protein 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
soluble enzyme form, in complex with inhibitor shows chelation of the active site magnesium
struktures of soluble isoforms in complex with inhibitors, S-adenosyl-L-methionine and Mg2+
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
V108M
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 5-7°C lower than that of wild type enzyme, and the free energy of unfolding at 25°C 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 37°C. The mutation is associated with increased risk of breast cancer and several neuropsychiatric disorders,
C95S
-
mutation increases the activity measured in absence of dithiothreitol in both the 108V and the 108M variant
V158M
the mutation affects directly COMT enzyme activity, the COMT polymorphism is unconnected to cold pain
Y71X
-
the mutation is predicted to truncate the protein before the catalytic domain likely affecting methyltransferase activity
additional information
-
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50 - 60
wild type soluble COMT loses most of the native helical structure in a sharp melting transition between 50 and 60°C
37
additional information
-
variants 108M and 108V differ in their thermal stability with COMT losing catalytic activity more rapidly
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine significantly stabilizes the secondary structures of the wild type enzyme
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 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
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant protein, by arginine-affinity chromatography. Loading of 4 mg of total protein lysate leads to recovery of a purified fraction with a total bioactivity recovery of 24% and a purification fold of 4.95
TALON metal affinity resin column chromatography, Superdex 75 gel filtration
purification of recombinant human soluble COMT using hydrophobic interaction chromatography, as the main isolation method, from an Escherichia coli culture broth
-
recombinant membrane-bound isoform, by arginine-affinity chromatography. Optimized conditions for isolation and purification consist in loading of 4 mg of total protein onto the column previously equilibrated at 20 °C and recovery of enzyme in a purified fraction using 500 mM NaCl, 10 mM DTT and 0.5% (v/v) Triton X-100 in 10 mM Tris buffer (pH 7) with a total bioactivity recovery of 24% and 4.95fold purification
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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
-
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
-
COMT protein expression is up-regulated in the proliferative phase of the menstrual cycyle, estrogen up-regulates soluble COMT protein expression
-
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
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
inhibition of catechol-O-methyltransferase enzyme by entacapone decreases the antiproliferative effects of fisetin and quercetin on Hep-G2 cells
analysis
medicine
synthesis
-
predictive artificial neural network models of the soluble COMT activity for production in a batch Escherichia coli culture process. Models predict a maximum COMT activity of 183.73 nmol/h, at 40°C, pH 6.5 and stirring rate of 351 rpm, and 132.90 nmol/h, at 35°C, pH 6.2 and stirring rate of 351 rpm, for semi-defined and complex medium, respectively. These results represent a 4fold increase in total activity by comparison to the standard operational conditions
analysis
-
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
-
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
-
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
-
inhibition of catechol-O-methyltransferase is an important approach in the treatment of Parkinson's disease
medicine
-
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
-
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
-
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
-
COMT activity and increased formation of depurinating adducts can be critical factors leading to initiation of breast cancer
medicine
-
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
-
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
-
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
-
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
-
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
-
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
-
the COMT Val158Met polymorphism is associated with fracture risk in elderly men, through a mechanism independent of bone mineral density
medicine
-
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
-
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
-
best-characterized single nucleotide polymorphism of the COMT gene consists of a valine-to-methionine substitution at codon 108/158. In homozygous carriers of Met, but not Val alleles, the activity of COMT and methionine sulfoxide reductase are significantly correlated throughout all tested brain regions
medicine
-
both melanotic melanoma SK-mel-1 and Ha-Cat cells express COMT activity. In SK-mel-1, COMT activity is reduced nearly 50% both 24 h and 48 h after a high dose UVB. In Ha-Cat cells, COMT activity increases 24 h after a high dose UVB but decreases at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. High concentrations of tolcapone reduce melanin levels in melanoma cells parallel to reduced cell numbers
medicine
-
enzymatic activities of functional COMT single-nucleotide polymorphisms in red blood cells in 24 healthy human volunteers, supplemented with750 mg of epigallocatechin-3-gallate.The homozygousVal-Met substitution in the SNPrs 4680 results in significantly decreased COMT activity. Enzymatic COMT activities are also affected by the other COMT polymorphisms. Epigallocatechin-3-gallate plasma levels significantly increase after intervention.They are not influenced by any of the COMT SNPs and different enzyme activities. Ingestion of 750 mg epigallocatechin-3-gallate does not result in impairment of COMT activity. However, COMT activity is significantly increased by 24% after epigallocatechin-3-gallate consumption
medicine
-
subjects carrying the Val/Val genotype of the Val108/158Met polymorphism show increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs placebo, whereas subjects carrying the Met/Met genotype react similarly to green tea and placebo ingestion. The differences in responses are due to the different responses on PL ingestion, but similar responses to green tea ingestion. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for energy expenditure and fat oxidation after green tea treatment
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Axelrod, J.; Tomchick, R.
Enzymatic O-methylation of epinephrine and other catechols
J. Biol. Chem.
233
702-705
1958
Bos taurus, Cavia porcellus, Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Huh, M.M.O.; Friedhoff, A.J.
Multiple molecular forms of catechol-O-methyltransferase. Evidence for two distinct forms, and their purification and physical characterization
J. Biol. Chem.
254
299-308
1979
Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus
Bhaird, N.N.; Tipton, K.F.
Catechol-O-methyltransferase from human placenta: purification and some properties
Biochem. Soc. Trans.
19
20S
1991
Homo sapiens
Lundstrm, K.; Tilgmann, C.; Pernen, J.; Kalkkinen, N.; Ulmanen, I.
Expression of enzymatically active rat liver and human placental catechol-O-methyltransferase in Escherichia coli; purification and partial characterization of the enzyme
Biochim. Biophys. Acta
1129
149-154
1992
Homo sapiens, Rattus norvegicus
Bertocci, B.; Garotta, G.; Da Prada, M.; Lahm, H.W.; Zurcher, G.; Virgallita, G.; Miggiano, V.
Immunoaffinity purification and partial amino acid sequence analysis of catechol-O-methyltransferase from pig liver
Biochim. Biophys. Acta
1080
103-109
1991
Homo sapiens, Sus scrofa
Tilgmann, C.; Kalkkinen, N.
Purification and partial sequence analysis of the soluble catechol-O-methyltransferase from human placenta: comparison to the rat liver enzyme
Biochem. Biophys. Res. Commun.
174
995-1002
1991
Homo sapiens
Ball, P.; Knuppen, R.; Haupt, M.; Breuer, H.
Kinetic properties of a soluble catechol O-methyltransferase of human liver
Eur. J. Biochem.
26
560-569
1972
Homo sapiens
Rivett, A.J.; Roth, J.A.
Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase
Biochemistry
21
1740-1742
1982
Homo sapiens
Tilgmann, C.; Kalkkinen, N.
Purification and partial characterization of rat liver soluble catechol-O-methyltransferase
FEBS Lett.
264
95-99
1990
Homo sapiens, Rattus norvegicus
Lin, R.L.; Narasimhachari, N.
Specific tlc, gc, and gc-ms methods for kinetic studies with COMT
Anal. Biochem.
57
46-58
1974
Homo sapiens, Platyrrhini
Nic A'Bhaird, N.; Tipton, K.F.
Behavior and properties of catechol-O-methyltransferase from human placenta
J. Neural Transm.
32
359-368
1990
Homo sapiens
Jeffrey, D.R.; Roth, J.A.
Purification and kinetic mechanism of human brain soluble catechol-O-methyltransferase
J. Neurochem.
44
881-885
1985
Homo sapiens
Jeffrey, D.R.; Roth, J.A.
Characterization of membrane-bound and soluble catechol-O-methyltransferase from human frontal cortex
J. Neurochem.
42
826-832
1984
Homo sapiens
Vidgren, J.; Svensson, L.A.; Liljas, A.
Crystal structure of catechol O-methyltransferase
Nature
368
354-358
1994
Homo sapiens
Ulmanen, I.; Peranen, J.; Tenhunen, J.; Tilgmann, C.; Karhunen, T.; Panula, P.; Bernasconi, L.; Aubry, J.P.; Lundstrom, K.
Expression and intracellular localization of catechol O-methyltransferase in transfected mammalian cells
Eur. J. Biochem.
243
452-459
1997
Homo sapiens, Rattus norvegicus
Weinshilboum, R.M.; Otterness, D.M.; Szumlanski, C.L.
Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase
Annu. Rev. Pharmacol. Toxicol.
39
19-52
1999
Rattus norvegicus, Homo sapiens (P21964)
Yan, M.; Webster, L.T., Jr.; Blumer, J.L.
Kinetic interactions of dopamine and dobutamine with human catechol-O-methyltransferase and monoamine oxidase in vitro
J. Pharmacol. Exp. Ther.
301
315-321
2002
Homo sapiens
Lotta, T.; Vidgren, J.; Tilgmann, C.; Ulmanen, I.; Melen, K.; Julkunen, I.; Taskinen, J.
Kinetics of human soluble and membrane-bound catechol O-methyltransferase: A revised mechanism and description of the thermolabile variant of the enzyme
Biochemistry
34
4202-4210
1995
Homo sapiens
Zhu, B.T.; Patel, U.K.; Cai, M.X.; Conney, A.H.
O-Methylation of tea polyphenols catalyzed by human placental cytosolic catechol-O-methyltransferase
Drug Metab. Dispos.
28
1024-1030
2000
Homo sapiens
Eshleman, A.J.; Stewart, E.; Evenson, A.K.; Mason, J.N.; Blakely, R.D.; Janowsky, A.; Neve, K.A.
Metabolism of catecholamines by catechol-O-methyltransferase in cells expressing recombinant catecholamine transporters
J. Neurochem.
69
1459-1466
1997
Homo sapiens
Tilgmann, C.; Ulmanen, I.
Purification methods of mammalian catechol-O-methyltransferases
J. Chromatogr. B
684
147-161
1996
Homo sapiens, Rattus norvegicus
Dawling, S.; Roodi, N.; Mernaugh, R.L.; Wang, X.; Parl, F.F.
Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol estrogens: comparison of wild-type and variant COMT isoforms
Cancer Res.
61
6716-6722
2001
Homo sapiens
Zhao, W.Q.; Latinwo, L.; Liu, X.X.; Lee, E.S.; Lamango, N.; Charlton, C.G.
L-Dopa upregulates the expression and activities of Methionine adenosyl transferase and catechol-O-methyltransferase
Exp. Neurol.
171
127-138
2001
Homo sapiens
Chen, J.; Lipska, B.K.; Halim, N.; Ma, Q.D.; Matsumoto, M.; Melhem, S.; et al.
Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain
Am. J. Hum. Genet.
75
807-821
2004
Homo sapiens
Wang, S.H.; Kuo, S.C.; Chen, S.C.
High-performance liquid chromatography determination of methionine adenosyltransferase activity using catechol-O-methyltransferase-coupled fluorometric detection
Anal. Biochem.
319
13-20
2003
Homo sapiens
Chen, D.; Wang, C.Y.; Lambert, J.D.; Ai, N.; Welsh, W.J.; Yang, C.S.
Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies
Biochem. Pharmacol.
69
1523-1531
2005
Homo sapiens
Lambert, J.D.; Chen, D.; Wang, C.Y.; Ai, N.; Sang, S.; Ho, C.T.; Welsh, W.J.; Yang, C.S.
Benzotropolone inhibitors of estradiol methylation: kinetics and in silico modeling studies
Bioorg. Med. Chem.
13
2501-2507
2005
Homo sapiens
Yao, J.; Li, Y.; Chang, M.; Wu, H.; Yang, X.; Goodman, J.E.; Liu, X.; Liu, H.; Mesecar, A.D.; Van Breemen, R.B.; Yager, J.D.; Bolton, J.L.
Catechol estrogen 4-hydroxyequilenin is a substrate and an inhibitor of catechol-O-methyltransferase
Chem. Res. Toxicol.
16
668-675
2003
Homo sapiens
Taskinen, J.; Ethell, B.T.; Pihlavisto, P.; Hood, A.M.; Burchell, B.; Coughtrie, M.W.H.
Conjugation of catechols by recombinant human sulfotransferases, UDP-glucuronosyltransferases, and soluble catechol O-methyltransferase: structure-conjugation relationships and predictive models
Drug Metab. Dispos.
31
1187-1197
2003
Homo sapiens (P21964), Homo sapiens
Lu, H.; Meng, X.; Yang, C.S.
Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (-)-epigallocatechin gallate
Drug Metab. Dispos.
31
572-579
2003
Homo sapiens, Rattus norvegicus, Sus scrofa
Nagai, M.; Conney, A.H.; Zhu, B.T.
Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase
Drug Metab. Dispos.
32
497-504
2004
Homo sapiens
Cotton, N.J.; Stoddard, B.; Parson, W.W.
Oxidative inhibition of human soluble catechol-O-methyltransferase
J. Biol. Chem.
279
23710-23718
2004
Homo sapiens
Lerner, C.; Masjost, B.; Ruf, A.; Gramlich, V.; Jakob-Roetne, R.; Zurcher, G.; Borroni, E.; Diederich, F.
Bisubstrate inhibitors for the enzyme catechol-O-methyltransferase (COMT): influence of inhibitor preorganisation and linker length between the two substrate moieties on binding affinity
Org. Biomol. Chem.
1
42-49
2003
Homo sapiens
van Duursen, M.B.; Sanderson, J.T.; de Jong, P.C.; Kraaij, M.; van den Berg, M.
Phytochemicals inhibit catechol-O-methyltransferase activity in cytosolic fractions from healthy human mammary tissues: implications for catechol estrogen-induced DNA damage
Toxicol. Sci.
81
316-324
2004
Homo sapiens
Mantione, K.J.; Cadet, P.; Zhu, W.; Kream, R.M.; Sheehan, M.; Fricchione, G.L.; Goumon, Y.; Esch, T.; Stefano, G.B.
Endogenous morphine signaling via nitric oxide regulates the expression of CYP2D6 and COMT: autocrine/paracrine feedback inhibition
Addict. Biol.
13
118-123
2008
Homo sapiens
Baud, P.; Courtet, P.; Perroud, N.; Jollant, F.; Buresi, C.; Malafosse, A.
Catechol-O-methyltransferase polymorphism (COMT) in suicide attempters: a possible gender effect on anger traits
Am. J. Med. Genet. B Neuropsychiatr. Genet.
144B
1042-1047
2007
Homo sapiens
Domschke, K.; Deckert, J.; Odonovan, M.C.; Glatt, S.J.
Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity
Am. J. Med. Genet. B Neuropsychiatr. Genet.
144B
667-673
2007
Homo sapiens
Pelayo-Teran, J.M.; Crespo-Facorro, B.; Carrasco-Marin, E.; Perez-Iglesias, R.; Mata, I.; Arranz, M.J.; Leyva-Cobian, F.; Vazquez-Barquero, J.L.
Catechol-O-methyltransferase Val158Met polymorphism and clinical characteristics in first episode non-affective psychosis
Am. J. Med. Genet. B Neuropsychiatr. Genet.
147B
550-556
2008
Homo sapiens
Halleland, H.; Lundervold, A.J.; Halmy, A.; Haavik, J.; Johansson, S.
Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults
Am. J. Med. Genet. B Neuropsychiatr. Genet.
150B
403-410
2009
Homo sapiens
Barnett, J.H.; Heron, J.; Ring, S.M.; Golding, J.; Goldman, D.; Xu, K.; Jones, P.B.
Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children
Am. J. Psychiatry
164
142-149
2007
Homo sapiens
Ozkan-Ariksoysal, D.; Tezcanli, B.; Kosova, B.; Ozsoz, M.
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
Anal. Chem.
80
588-596
2008
Homo sapiens
Lehmann, L.; Jiang, L.; Wagner, J.
Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured MCF-7 cells
Carcinogenesis
29
363-370
2008
Homo sapiens
Bai, H.W.; Shim, J.Y.; Yu, J.; Zhu, B.T.
Biochemical and molecular modeling studies of the O-methylation of various endogenous and exogenous catechol substrates catalyzed by recombinant human soluble and membrane-bound catechol-O-methyltransferases
Chem. Res. Toxicol.
20
1409-1425
2007
Homo sapiens
Zoccolella, S.; Iliceto, G.; deMari, M.; Livrea, P.; Lamberti, P.
Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
Clin. Chem. Lab. Med.
45
1607-1613
2007
Homo sapiens
Bonifacio, M.J.; Palma, P.N.; Almeida, L.; Soares-da-Silva, P.
Catechol-O-methyltransferase and its inhibitors in Parkinsons disease
CNS Drug Rev.
13
352-379
2007
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Sus scrofa, Rattus norvegicus (P22734)
Apud, J.A.; Weinberger, D.R.
Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors
CNS Drugs
21
535-557
2007
Homo sapiens
Zahid, M.; Saeed, M.; Lu, F.; Gaikwad, N.; Rogan, E.; Cavalieri, E.
Inhibition of catechol-O-methyltransferase increases estrogen-DNA adduct formation
Free Radic. Biol. Med.
43
1534-1540
2007
Homo sapiens
Hirano, Y.; Tsunoda, M.; Shimosawa, T.; Matsui, H.; Fujita, T.; Funatsu, T.
Suppression of catechol-O-methyltransferase activity through blunting of alpha2-adrenoceptor can explain hypertension in Dahl salt-sensitive rats
Hypertens. Res.
30
269-278
2007
Homo sapiens, Rattus norvegicus
Cheon, K.A.; Jun, J.Y.; Cho, D.Y.
Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder
Int. Clin. Psychopharmacol.
23
291-298
2008
Homo sapiens
Savitz, J.B.; van der Merwe, L.; Newman, T.K.; Solms, M.; Stein, D.J.; Ramesar, R.S.
The relationship between childhood abuse and dissociation. Is it influenced by catechol-O-methyltransferase (COMT) activity?
Int. J. Neuropsychopharmacol.
11
149-161
2008
Homo sapiens
Lorentzon, M.; Eriksson, A.L.; Nilsson, S.; Mellstroem, D.; Ohlsson, C.
Association between physical activity and BMD in young men is modulated by catechol-O-methyltransferase (COMT) genotype: the GOOD study
J. Bone Miner. Res.
22
1165-1172
2007
Homo sapiens
Passarinha, L.A.; Bonifacio, M.J.; Soares-da-Silva, P.; Queiroz, J.A.
A new approach on the purification of recombinant human soluble catechol-O-methyltransferase from an Escherichia coli extract using hydrophobic interaction chromatography
J. Chromatogr. A
1177
287-296
2008
Homo sapiens
Stolk, L.; van Meurs, J.B.; Jhamai, M.; Arp, P.P.; van Leeuwen, J.P.; Hofman, A.; de Jong, F.H.; Pols, H.A.; Uitterlinden, A.G.
The catechol-O-methyltransferase Met158 low-activity allele and association with nonvertebral fracture risk in elderly men
J. Clin. Endocrinol. Metab.
92
3206-3212
2007
Homo sapiens
Rutherford, K.; Le Trong, I.; Stenkamp, R.E.; Parson, W.W.
Crystal structures of human 108V and 108M catechol O-methyltransferase
J. Mol. Biol.
380
120-130
2008
Sus scrofa, Homo sapiens (P21964), Homo sapiens, Rattus norvegicus (P22734)
Tan, H.Y.; Chen, Q.; Goldberg, T.E.; Mattay, V.S.; Meyer-Lindenberg, A.; Weinberger, D.R.; Callicott, J.H.
Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory
J. Neurosci.
27
13393-13401
2007
Homo sapiens
Williams-Gray, C.H.; Hampshire, A.; Robbins, T.W.; Owen, A.M.; Barker, R.A.
Catechol O-methyltransferase Val158Met genotype influences frontoparietal activity during planning in patients with Parkinsons disease
J. Neurosci.
27
4832-4838
2007
Homo sapiens
Papaleo, F.; Crawley, J.N.; Song, J.; Lipska, B.K.; Pickel, J.; Weinberger, D.R.; Chen, J.
Genetic dissection of the role of catechol-O-methyltransferase in cognition and stress reactivity in mice
J. Neurosci.
28
8709-8723
2008
Homo sapiens (P21964), Homo sapiens
Lu, F.; Zahid, M.; Saeed, M.; Cavalieri, E.L.; Rogan, E.G.
Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction and catechol-O-methyltransferase inhibition
J. Steroid Biochem. Mol. Biol.
105
150-158
2007
Homo sapiens
Babovic, D.; OTuathaigh, C.M.; OConnor, A.M.; OSullivan, G.J.; Tighe, O.; Croke, D.T.; Karayiorgou, M.; Gogos, J.A.; Cotter, D.; Waddington, J.L.
Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase
Neuroscience
155
1021-1029
2008
Homo sapiens, Mus musculus
Ronkainen, P.H.; Poellaenen, E.; Toermaekangas, T.; Tiainen, K.; Koskenvuo, M.; Kaprio, J.; Rantanen, T.; Sipilae, S.; Kovanen, V.
Catechol-O-methyltransferase gene polymorphism is associated with skeletal muscle properties in older women alone and together with physical activity
PLoS ONE
3
e1819
2008
Homo sapiens
Crespo-Facorro, B.; Roiz-Santianez, R.; Pelayo-Teran, J.M.; Perez-Iglesias, R.; Carrasco-Marin, E.; Mata, I.; Gonzalez-Mandly, A.; Jorge, R.; Vazquez-Barquero, J.L.
Low-activity allele of catechol-O-methyltransferase (COMTL) is associated with increased lateral ventricles in patients with first episode non-affective psychosis
Prog. Neuropsychopharmacol. Biol. Psychiatry
31
1514-1518
2007
Homo sapiens (P21964), Homo sapiens
Roussos, P.; Giakoumaki, S.G.; Rogdaki, M.; Pavlakis, S.; Frangou, S.; Bitsios, P.
Prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism
Psychol. Med.
38
1651-1658
2008
Homo sapiens
Doyle, A.; Yager, J.
Catechol-O-methyltransferase: Effects of the val108met polymorphism on protein turnover in human cells
Biochim. Biophys. Acta
1780
27-33
2008
Homo sapiens
Rutherford, K.; Alphandery, E.; McMillan, A.; Daggett, V.; Parson, W.W.
The V108M mutation decreases the structural stability of catechol O-methyltransferase
Biochim. Biophys. Acta
1784
1098-1105
2008
Homo sapiens (P21964), Homo sapiens
Huo, C.; Yang, H.; Cui, Q.C.; Dou, Q.P.; Chan, T.H.
Proteasome inhibition in human breast cancer cells with high catechol-O-methyltransferase activity by green tea polyphenol EGCG analogs
Bioorg. Med. Chem.
18
1252-1258
2010
Homo sapiens
Ross, J.R.; Riley, J.; Taegetmeyer, A.B.; Sato, H.; Gretton, S.; du Bois, R.M.; Welsh, K.I.
Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects
Cancer
112
1390-1403
2008
Homo sapiens
Meyer, M.R.; Maurer, H.H.
Enantioselectivity in the methylation of the catecholic phase I metabolites of methylenedioxy designer drugs and their capability to inhibit catechol-O-methyltransferase-catalyzed dopamine 3-methylation
Chem. Res. Toxicol.
22
1205-1211
2009
Homo sapiens
Ho, P.W.; Chu, A.C.; Kwok, K.H.; Liu, H.F.; Kung, M.H.; Ramsden, D.B.; Ho, S.L.
Effects of plasticisers and related compounds on the expression of the soluble form of catechol-O-methyltransferase in MCF-7 cells
Curr. Drug Metab.
9
276-279
2008
Homo sapiens
Ho, P.W.; Garner, C.E.; Ho, J.W.; Leung, K.C.; Chu, A.C.; Kwok, K.H.; Kung, M.H.; Burka, L.T.; Ramsden, D.B.; Ho, S.L.
Estrogenic phenol and catechol metabolites of PCBs modulate catechol-O-methyltransferase expression via the estrogen receptor: potential contribution to cancer risk
Curr. Drug Metab.
9
304-309
2008
Homo sapiens
Salih, S.; Salama, S.; Fadl, A.; Nagamani, M.; Al-Hendy, A.
Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma
Fertil. Steril.
90
789-797
2008
Homo sapiens
Salama, S.A.; Kamel, M.; Awad, M.; Nasser, A.H.; Al-Hendy, A.; Botting, S.; Arrastia, C.
Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cells: protective effect of catechol-O-methyltransferase
Int. J. Cancer
123
1246-1254
2008
Homo sapiens
Zhu, B.T.; Wang, P.; Nagai, M.; Wen, Y.; Bai, H.W.
Inhibition of human catechol-O-methyltransferase (COMT)-mediated O-methylation of catechol estrogens by major polyphenolic components present in coffee
J. Steroid Biochem. Mol. Biol.
113
65-74
2009
Homo sapiens
Yasuda, S.; Yasuda, T.; Hui, Y.; Liu, M.Y.; Suiko, M.; Sakakibara, Y.; Liu, M.C.
Concerted action of the cytosolic sulfotransferase, SULT1A3, and catechol-O-methyltransferase in the metabolism of dopamine in SK-N-MC human neuroblastoma cells
Neurosci. Res.
64
273-279
2009
Homo sapiens
Sand, P.; Korte, G.; Domani, M.; Konstandin, N.; Karl, A.; Wagner, K.; Dinnbier, M.
Alternatively spliced human catechol-O-methyltransferase (COMT) rationalizes lack of Val158Met effects on pain tolerance
Pain
136
445-446
2008
Homo sapiens (A3F6Y9), Homo sapiens
Salama, S.A.; Kamel, M.W.; Botting, S.; Salih, S.M.; Borahay, M.A.; Hamed, A.A.; Kilic, G.S.; Saeed, M.; Williams, M.Y.; Diaz-Arrastia, C.R.
Catechol-O-methyltransferase expression and 2-methoxyestradiol affect microtubule dynamics and modify steroid receptor signaling in leiomyoma cells
PLoS ONE
4
e7356
2009
Homo sapiens
Du, X.; Schwander, M.; Moresco, E.M.; Viviani, P.; Haller, C.; Hildebrand, M.S.; Pak, K.; Tarantino, L.; Roberts, A.; Richardson, H.; Koob, G.; Najmabadi, H.; Ryan, A.F.; Smith, R.J.; Mueller, U.; Beutler, B.
A catechol-O-methyltransferase that is essential for auditory function in mice and humans
Proc. Natl. Acad. Sci. USA
105
14609-14614
2008
Homo sapiens, Mus musculus
Rautio, J.; Leppaenen, J.; Lehtonen, M.; Laine, K.; Koskinen, M.; Pystynen, J.; Savolainen, J.; Sairanen, M.
Design, synthesis and in vitro/in vivo evaluation of orally bioavailable prodrugs of a catechol-O-methyltransferase inhibitor
Bioorg. Med. Chem. Lett.
20
2614-2616
2010
Homo sapiens
Zhu, B.T.; Wu, K.Y.; Wang, P.; Cai, M.X.; Conney, A.H.
O-methylation of catechol estrogens by human placental catechol-o-methyltransferase: interindividual differences in sensitivity to heat inactivation and to inhibition by dietary polyphenols
Drug Metab. Dispos.
38
1892-1899
2010
Homo sapiens
Robinson, R.G.; Smith, S.M.; Wolkenberg, S.E.; Kandebo, M.; Yao, L.; Gibson, C.R.; Harrison, S.T.; Polsky-Fisher, S.; Barrow, J.C.; Manley, P.J.; Mulhearn, J.J.; Nanda, K.K.; Schubert, J.W.; Trotter, B.W.; Zhao, Z.; Sanders, J.M.; Smith, R.F.; McLoughlin, D.; Sharma, S.; Hall, D.L.; Walker, T.L.; Kershner, J.L.; , B.
Characterization of non-nitrocatechol pan and isoform specific catechol-O-methyltransferase inhibitors and substrates
ACS Chem. Neurosci.
3
129-140
2012
Homo sapiens, Rattus norvegicus
Kurogi, K.; Alazizi, A.; Liu, M.Y.; Sakakibara, Y.; Suiko, M.; Sugahara, T.; Liu, M.C.
Concerted actions of the catechol O-methyltransferase and the cytosolic sulfotransferase SULT1A3 in the metabolism of catecholic drugs
Biochem. Pharmacol.
84
1186-1195
2012
Homo sapiens
Pedro, A.; Pereira, P.; Bonifacio, M.; Queiroz, J.; Passarinha, L.
Purification of membrane-bound catechol-O-methyltransferase by arginine-affinity chromatography
Chromatographia
78
1339-1348
2015
Homo sapiens
-
Weinert, C.; Wiese, S.; Rawel, H.; Esatbeyoglu, T.; Winterhalter, P.; Homann, T.; Kulling, S.
Methylation of catechins and procyanidins by rat and human catechol-o-methyltransferase: Metabolite profiling and molecular modeling studies
Drug Metab. Dispos.
40
353-359
2012
Homo sapiens, Rattus norvegicus
Lorenz, M.; Paul, F.; Moobed, M.; Baumann, G.; Zimmermann, B.F.; Stangl, K.; Stangl, V.
The activity of catechol-O-methyltransferase (COMT) is not impaired by high doses of epigallocatechin-3-gallate (EGCG) in vivo
Eur. J. Pharmacol.
740
645-651
2014
Homo sapiens
Silva, R.; Ferreira, S.; Bonifacio, M.J.; Dias, J.M.; Queiroz, J.A.; Passarinha, L.A.
Optimization of fermentation conditions for the production of human soluble catechol-O-methyltransferase by Escherichia coli using artificial neural network
J. Biotechnol.
160
161-168
2012
Homo sapiens
Moskovitz, J.; Walss-Bass, C.; Cruz, D.A.; Thompson, P.M.; Hairston, J.; Bortolato, M.
The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion
Neuropathol. Appl. Neurobiol.
41
941-951
2015
Homo sapiens
Zhu, X.; Jia, Y.H.
Inhibition of catechol-O-methyltransferase (COMT) by myricetin, dihydromyricetin, and myricitrin
Pharmazie
69
183-186
2014
Homo sapiens
Magina, S.; Vieira-Coelho, M.A.; Serrao, M.P.; Kosmus, C.; Moura, E.; Moura, D.
Ultraviolet B radiation differentially modifies catechol-O-methyltransferase activity in keratinocytes and melanoma cells
Photodermatol. Photoimmunol. Photomed.
28
137-141
2012
Homo sapiens
Sparta, M.; Alexandrova, A.N.
How metal substitution affects the enzymatic activity of catechol-O-methyltransferase
PLoS ONE
7
e47172
2012
Homo sapiens (P21964)
Hursel, R.; Janssens, P.L.; Bouwman, F.G.; Mariman, E.C.; Westerterp-Plantenga, M.S.
The role of catechol-O-methyl transferase Val(108/158)Met polymorphism (rs4680) in the effect of green tea on resting energy expenditure and fat oxidation: a pilot study
PLoS ONE
9
e106220
2014
Homo sapiens
Suriguga, M.; Li, X.F.; Li, Y.; Yu, C.H.; Li, Y.R.; Yi, Z.C.
The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells
Toxicol. Appl. Pharmacol.
273
635-643
2013
Homo sapiens
Harrison, S.T.; Poslusney, M.S.; Mulhearn, J.J.; Zhao, Z.; Kett, N.R.; Schubert, J.W.; Melamed, J.Y.; Allison, T.J.; Patel, S.B.; Sanders, J.M.; Sharma, S.; Smith, R.F.; Hall, D.L.; Robinson, R.G.; Sachs, N.A.; Hutson, P.H.; Wolkenberg, S.E.; Barrow, J.C.
Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT)
ACS Med. Chem. Lett.
6
318-323
2015
Homo sapiens (P21964)
Poor, M.; Zrinyi, Z.; K?szegi, T.
Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells Metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT)
Biomed. Pharmacother.
83
998-1005
2016
Homo sapiens (P21964)
Zhao, Z.; Harrison, S.T.; Schubert, J.W.; Sanders, J.M.; Polsky-Fisher, S.; Zhang, N.R.; McLoughlin, D.; Gibson, C.R.; Robinson, R.G.; Sachs, N.A.; Kandebo, M.; Yao, L.; Smith, S.M.; Hutson, P.H.; Wolkenberg, S.E.; Barrow, J.C.
Synthesis and optimization of N-heterocyclic pyridinones as catechol-O-methyltransferase (COMT) inhibitors
Bioorg. Med. Chem. Lett.
26
2952-2956
2016
Homo sapiens (P21964)
Pedro, A.; Pereira, P.; Bonifacio, M.; Queiroz, J.; Passarinha, L.
Purification of membrane-bound catechol-O-methyltransferase by arginine-affinity chromatography
Chromatographia
78
1339-1348
2015
Homo sapiens (P21964)
-
Buchler, I.; Akuma, D.; Au, V.; Carr, G.; de Leon, P.; DePasquale, M.; Ernst, G.; Huang, Y.; Kimos, M.; Kolobova, A.; Poslusney, M.; Wei, H.; Swinnen, D.; Montel, F.; Moureau, F.; Jigorel, E.; Schulze, M.E.D.; Wood, M.; Barrow, J.C.
Optimization of 8-hydroxyquinolines as inhibitors of catechol O-methyltransferase
J. Med. Chem.
61
9647-9665
2018
Homo sapiens (P21964)
Ikeda, M.; Iijima, H.; Shinoda, I.; Iwamoto, H.; Takeda, Y.
Inhibitory effect of bovine lactoferrin on catechol-O-methyltransferase
Molecules
22
1373
2017
Homo sapiens (P21964)
Patra, N.; Ioannidis, E.I.; Kulik, H.J.
Computational investigation of the interplay of substrate positioning and reactivity in catechol O-methyltransferase
PLoS ONE
11
e0161868
2016
Homo sapiens (P21964)
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