1.14.16.2: tyrosine 3-monooxygenase
This is an abbreviated version!
For detailed information about tyrosine 3-monooxygenase, go to the full flat file.
Word Map on EC 1.14.16.2
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1.14.16.2
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dopamine
-
dopaminergic
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parkinsonism
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nigra
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striatum
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catecholamine
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substantia
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nerve
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ventral
-
fiber
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sympathetic
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innervation
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adrenal
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noradrenergic
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neurotransmitter
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6-hydroxydopamine
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ganglia
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th-positive
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catecholaminergic
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neuropeptide
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norepinephrine
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nigrostriatal
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midbrain
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monoamine
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neurotrophic
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compacta
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coeruleus
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hypothalamus
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tegmental
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mesencephalic
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1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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l-dopa
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6-ohda
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neurochemical
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accumbens
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noradrenaline
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rostrally
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dopac
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apomorphine
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perikarya
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intrastriatal
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beta-hydroxylase
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mptp-induced
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varicosity
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ventrolateral
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dopamine-beta-hydroxylase
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preoptic
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npy
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phenylethanolamine
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analysis
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diagnostics
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homovanillic
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synthesis
- 1.14.16.2
- dopamine
-
dopaminergic
- parkinsonism
- nigra
- striatum
- catecholamine
-
substantia
- nerve
-
ventral
- fiber
-
sympathetic
-
innervation
- adrenal
-
noradrenergic
-
neurotransmitter
- 6-hydroxydopamine
- ganglia
-
th-positive
-
catecholaminergic
-
neuropeptide
- norepinephrine
-
nigrostriatal
- midbrain
-
monoamine
-
neurotrophic
- compacta
- coeruleus
- hypothalamus
- tegmental
-
mesencephalic
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- l-dopa
-
6-ohda
-
neurochemical
- accumbens
- noradrenaline
-
rostrally
-
dopac
- apomorphine
- perikarya
-
intrastriatal
- beta-hydroxylase
-
mptp-induced
-
varicosity
-
ventrolateral
- dopamine-beta-hydroxylase
-
preoptic
- npy
- phenylethanolamine
- analysis
- diagnostics
-
homovanillic
- synthesis
Reaction
Synonyms
CAT-2, DTH1, DTH2, hTH2, L-tyrosine hydroxylase, monophenol monooxygenase, oxygenase, tyrosine 3-mono-, TH, TH1, TH2, TyrH, tyrosinase, tyrosine 3-hydroxylase, tyrosine 3-monooxygenase, tyrosine hydroxylase, tyrosine hydroxylase type 1, tyrosine-3-mono-oxygenase, tyrosine-3-monooxygenase
ECTree
1.14.16.2 tyrosine 3-monooxygenaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 1.14.16.2 - tyrosine 3-monooxygenase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin
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80% inhibition when the enzyme is preincubated with (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin. Inhibition was attenuated by simultanious addition of dopamine
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
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i.e. BH4, cofactor, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, competitive inhibition, synergistically with DTT
(6S)-L-erythro-1',2'-dihydroxypropyltetrahydropterin
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80% inhibition when the enzyme is preincubated with (6S)-L-erythro-1',2'-dihydroxypropyltetrahydropterin
2,4-diamino-6-dihydroxypropyl-5,6,7,8-tetrahydropterin
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competitive against (6R)-L-erythro-tetrahydrobiopterin
5-methyl-5,6,7,8-tetrahydropterin
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competitive against (6R)-L-erythro-tetrahydrobiopterin
5-[(3-azido-6-nitrobenzylidene)amino]-2,6-diamino-4-pyrimidinone
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competitive against tetrahydrobiopterin
6-methyltetrahydropterin
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80% inhibition when the enzyme is preincubated with 6-methyltetrahydropterin
6-[2-(4-benzoylphenyl)propionyloxymethyl]-5,6,7,8-tetrahydropterin
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competitive against (6R)-L-erythro-tetrahydrobiopterin
7-amino-3,3a,4,5-tetrahydro-8H-2-oxa-5,6,8,9b-tetraaza-cyclopenta[a]naphthalene-1,9-dione
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competitive against (6R)-L-erythro-tetrahydrobiopterin
8-methyl-6,7-dimethyl-5,6,7,8-tetrahydropterin
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competitive against (6R)-L-erythro-tetrahydrobiopterin
alpha-methyl-L-tyrosine
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in vivo injection into the neurointermediate lobe of the pituitary gland, i.e. the intracerebro-ventricular and intra-arcuatus injection, leads to reduced synthesis of dopamine and DOPA, but not of norepinephrine, and leads to increased contents of pituitary prolactin, overview
endothelin-1
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effects of long-term modulation at different concentrations, overview
endothelin-2
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effects of long-term modulation at different concentrations, overview
guanidine hydrochloride
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no activity at guanidine hydrochloride concentrations exceeding 0.6 M
N-methyl-norsalsolinol
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noncompetitive with respect to L-tyrosine, N-methyl-norsalsolinol and related tetrahydroisoquinolines accumulate in the nigrostriatal system of the human brain and are increased in the cerebrospinal fluid of patients with Parkinsons disease
nociceptin/orphanin FQ-NOP receptor system
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activation of nociceptin/orphanin FQ-NOP receptor system inhibits tyrosine hydroxylase phosphorylation, dopamine synthesis and dopamine D1 receptor signaling in rat nucleus accumbens and dorsal striatum, N/OFQ preferentially inhibits phosphoSer40-enzyme in nucleus accumbens shell, overview
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norsalsolinol
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N-methyl-norsalsolinol and related tetrahydroisoquinolines accumulate in the nigrostriatal system of the human brain and are increased in the cerebrospinal fluid of patients with Parkinsons disease
salsolinol
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50% inhibition at 35.4 microM and 4.1 microM when assayed at 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine concentration of 0.5 mM or 0.25 mM, respectively
tetrahydrobiopterin
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substrate inhibition at tyrosine and O2 concentrations higher than 0.1 mM and 2.2 mM, respectively
3,4-dihydroxy-L-phenylalanine
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incubation with 3,4-dihydroxy-L-phenylalanine results in an inhibition of tyrosine hydroxylase activity in situ under both basal conditions and conditions that promote the phosphorylation of Ser40. 3,4-dihydroxy-L-phenylalanine binding to the high affinity site alone inhibits tyrosine hydroxylase activity to approximately 15% and 24% of control (non-dopamine bound) levels at 0.02 mM and 2.0 mM 5,6,7,8-tetrahydrobiopterin, respectively
3,4-dihydroxyphenylacetaldehyde
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potent inhibitor, 0.01 and 0.02 mM cause 66% and 75% inhibition, respectively
Catecholamines
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e.g. dopamine, feedback inhibition, phosphorylation by protein kinase A at Ser40, the most prominent of these regulatory sites, increases the dissociation rate of bound catecholamine inhibitors
dopamine
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feedback inhibition, in the presence of 0.02 mM dopamine tyrosine hydroxylase enzyme specific activity is reduced by about 60%
dopamine
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feedback inhibitor and catecholamine product, binding inhibits and stabilizes the enzyme, reversible and competitive inhibition with respect to tetrahydrobiopterin
dopamine
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binding kinetics and regulatory function, overview, phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme. Binding of dopamine to the high-affinity site also decreases Vmax and increases the Km for the cofactor tetrahydrobiopterin, while binding of dopamine to the low affinity site regulates tyrosine hydroxylase activity by increasing the Km for tetrahydrobiopterin
estradiol-17beta
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biphasic effects on in vivo and in vitro enzyme activity and kinetics. Low concentrations (1 nM) stimulate, and high concentrations (1 mM) inhibit
estradiol-17beta
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inhibiting at concetration above 0.5 mM. adenosine 3',5' cyclic monophosphate enhances the inhibition at high estradiol-17beta concentrations
L-Dopa
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above 0.15 mM inhibiting L-dopa-oxidase activity in presence of tetrahydropterin, but not with 6,7-dimethyltetrahydropterin
L-Dopa
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Increased levels of intracellular L-DOPA inhibits tyrosine hydroxylase activity by end-product inhibition at early time points, L-DOPA (20-200 microM) treatment leads to a 562%-937% increase in L-DOPA influx at 1 h, which inhibits the activity of tyrosine hydroylase during the same period.
additional information
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inhibition of cAMP-protein kinase A and protein kinase C in crude extracts significantly reduces tyrosine hydroxylase activity
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additional information
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no inhibition by nonhydroxylated N-methyl-1,2,3,4-tetrahydroisoquinoline
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additional information
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glial cell line-derived neurotrophic factor, GDNF, supresses the enzyme expression in the midbrain
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additional information
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phosphorylation at Ser40 activates the enzyme, the phosphorylation is inhibited by alpha-synuclein, up to 183% induced by amphetamines, the phosphorylation inhibition is inhibited by melatonin, mechanisms, overview
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additional information
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UO126 significantly inhibits the basal phosphorylation of Ser40 in isoform TH1, but does not inhibit the phosphorylation of Ser44 in isoform TH2
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additional information
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there is no significant decrease in tyrosine hydroxylase activity at 0.02 mM or 2.0 mM 5,6,7,8-tetrahydrobiopterin following ovalbumin-coated charcoal treatment
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additional information
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dephosphorylation of Ser40, by phosphatase PP2A, inhibits the enzyme, protein kinase Cdelta increases the inhibition by activating PP2A, and physically associates with the tyrosine hydroxylase
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additional information
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alpha-synuclein inhibits phosphorylation of the enzyme at Ser40 and enzyme activity, thereby regulating the dopamine level
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additional information
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alpha-synuclein inhibits the enzyme by inhibiting enzyme phosphorylation at Ser40 in the regulatory domain, aggregated alpha-Syn is no longer able to inhibit tyrosine hydroxylase, overview
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additional information
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PD-098059, compound C, i.e. 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine, and 5'-amino-5'-dAdo inhibit the activation of the enzyme by AMP-activated protein kinase, PD-098059 specifically inhibits phosphorylation at Ser31 without affecting phosphorylation at Ser19 and Ser40
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additional information
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chronic administration of the antipsychotic drug haloperidol causes a significant increase in locomotor activity and lower levels of tyrosine hydroxylase immunoreactivity in the caudate putamen of the striatum, another drug, quetiapine, does not cause effects to the same extent and protects the cell and tyrosine hydoxylase against oxidative stress-induced damage, overview
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additional information
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endothelin-1 and endothelin-3 inhibit the enzyme by inhibiting enzyme phosphorylation at Ser19, Ser31, and Ser40, but the response is abolished by selective ETA and ETB antagonists BQ-610 and BQ-788, respectively. The inhibitory effect of endothelins is also reversed by Nomega-nitro-L-arginine methyl ester and 7-nitroindazole, 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinozalin-1-one, and KT-5823, respectively, no inhibition of tyrosine hydroxylase by ETA and ETB selective agonists sarafotoxin S6b and IRL-1620, respectively, detailed overview
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additional information
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the tyrosine hydroxylase activity decreases in the hearts of rats administrated 7,12-dimethylbenz[a]anthracene + 1-isopropyl-3-methylbenzimidazole-2-selenone and 7,12-dimethylbenz[a]anthracene + 1,3-di-p-methoxybenzylpyrimidine-2-selenone according to 7,12-dimethylbenz[a]anthracene group
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