Literature summary for 2.1.1.6 extracted from

Bonifacio, M.J.; Palma, P.N.; Almeida, L.; Soares-da-Silva, P.
Catechol-O-methyltransferase and its inhibitors in Parkinsons disease (2007), CNS Drug Rev., 13, 352-379.

Inhibitors

Inhibitors	Comment	Organism
2-hydroxyoestrogen	-	Homo sapiens
ascorbic acid	-	Homo sapiens
caffeic acid	-	Homo sapiens
CGP 28014	-	Homo sapiens
entacapone	-	Homo sapiens
gallic acid	-	Homo sapiens
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	Homo sapiens
nebicapone	-	Homo sapiens
nitecapone	-	Homo sapiens
pyrogallol	-	Homo sapiens
quercetin	-	Homo sapiens
tolcapone	-	Homo sapiens
tropolone	-	Homo sapiens
U-0521	-	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.00015	-	2-hydroxyestradiol	membrane-bound enzyme form	Oryctolagus cuniculus
0.00027	-	2-hydroxyestradiol	soluble enzyme form	Oryctolagus cuniculus
0.0009	0.003	epinephrine	membrane-bound enzyme form	Rattus norvegicus
0.00091	-	isoproterenol	membrane-bound enzyme form	Oryctolagus cuniculus
0.0033	-	dopamine	membrane-bound enzyme form, brain	Homo sapiens
0.0055	0.114	norepinephrine	membrane-bound enzyme form	Rattus norvegicus
0.01	-	catechol	recombinant enzyme expressed in Escherichia coli, membrane-bound enzyme form	Homo sapiens
0.012	-	epinephrine	membrane-bound enzyme form	Mus musculus
0.015	-	dopamine	recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form	Homo sapiens
0.024	-	norepinephrine	recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form	Homo sapiens
0.043	-	R-salsolinol	membrane-bound enzyme form	Sus scrofa
0.108	-	catechol	recombinant enzyme expressed in Escherichia coli, soluble enzyme form	Homo sapiens
0.121	-	isoproterenol	soluble enzyme form	Oryctolagus cuniculus
0.156	-	R-salsolinol	soluble enzyme form	Sus scrofa
0.168	0.345	epinephrine	soluble enzyme form	Rattus norvegicus
0.207	-	dopamine	recombinant enzyme expressed in Sf9 cells, soluble enzyme form	Homo sapiens
0.242	-	epinephrine	soluble enzyme form	Mus musculus
0.266	-	levodopa	recombinant enzyme expressed in Sf9 cells, membrane-bound enzyme form	Homo sapiens
0.28	-	dopamine	soluble enzyme form, brain	Homo sapiens
0.304	0.464	norepinephrine	soluble enzyme form	Rattus norvegicus
0.369	-	norepinephrine	recombinant enzyme expressed in Sf9 cells, soluble enzyme form	Homo sapiens
0.613	-	levodopa	recombinant enzyme expressed in Sf9 cells, soluble enzyme form	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
membrane	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	Mus musculus	16020	-
membrane	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	Homo sapiens	16020	-
membrane	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	Sus scrofa	16020	-
membrane	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	Oryctolagus cuniculus	16020	-
membrane	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	Rattus norvegicus	16020	-
soluble	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Mus musculus	-	-
soluble	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Homo sapiens	-	-
soluble	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Sus scrofa	-	-
soluble	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Oryctolagus cuniculus	-	-
soluble	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Rattus norvegicus	-	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
24300	-	S-COMT	Homo sapiens
30000	-	MB-COMT	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Mus musculus	-	-	-
Oryctolagus cuniculus	-	-	-
Rattus norvegicus	P22734	-	-
Sus scrofa	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
additional information	S-COMT is a nonglycosylated protein	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
aorta	-	Oryctolagus cuniculus	-
brain	-	Homo sapiens	-
brain	-	Sus scrofa	-
brain	-	Rattus norvegicus	-
kidney	-	Rattus norvegicus	-
liver	-	Mus musculus	-
liver	-	Rattus norvegicus	-
placenta	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
S-adenosyl-L-methionine + 2-hydroxyestradiol	-	Oryctolagus cuniculus	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + catechol	-	Homo sapiens	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + dopamine	-	Homo sapiens	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + epinephrine	-	Mus musculus	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + epinephrine	-	Rattus norvegicus	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + isoproterenol	-	Oryctolagus cuniculus	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + levodopa	-	Homo sapiens	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + norepinephrine	-	Homo sapiens	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + norepinephrine	-	Rattus norvegicus	S-adenosyl-L-homocysteine + ?	-	?
S-adenosyl-L-methionine + R-salsolinol	-	Sus scrofa	S-adenosyl-L-homocysteine + ?	-	?

Synonyms

Synonyms	Comment	Organism
MB-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Mus musculus
MB-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Homo sapiens
MB-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Sus scrofa
MB-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Oryctolagus cuniculus
MB-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Rattus norvegicus
S-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Mus musculus
S-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Homo sapiens
S-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Sus scrofa
S-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Oryctolagus cuniculus
S-COMT	two molecular forms: a soluble form (S-COMT) and in another form associated with membranes (MB-COMT)	Rattus norvegicus

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.00027	-	tolcapone	-	Homo sapiens
0.0003	-	entacapone	-	Homo sapiens
0.00102	-	nitecapone	-	Homo sapiens