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Information on EC 1.14.16.2 - tyrosine 3-monooxygenase and Organism(s) Rattus norvegicus and UniProt Accession P04177
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1.14.16.2 tyrosine 3-monooxygenaseIUBMB Comments
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA carboxylase] kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
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Word Map
- 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
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
tyrosine hydroxylase, cat-2, tyrosine 3-monooxygenase, monophenol monooxygenase, tyrosine-3-monooxygenase, l-tyrosine hydroxylase, tyrosine 3-hydroxylase, tyrosine hydroxylase type 1, tyrosine-3-mono-oxygenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
tyrosine hydroxylase
-
L-tyrosine hydroxylase
oxygenase, tyrosine 3-mono-
-
-
-
-
tyrosine 3-hydroxylase
-
-
-
-
tyrosine hydroxylase
L-tyrosine hydroxylase
-
-
-
-
tyrosine hydroxylase
-
-
-
-
tyrosine hydroxylase
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
mechanism
L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
mechanism
-
L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
stereochemical analysis of ligand binding
-
L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
active binding site
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
reduction
-
-
-
-
oxidation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-tyrosine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA carboxylase] kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
CAS REGISTRY NUMBER
COMMENTARY
9036-22-0
-
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
L-phenylalanine + tetrahydropteridine + 2 O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + 2 H2O
wild-type and mutants
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
recombinant wild-type and mutant
-
?
L-tryptophan + 6-methyltetrahydrobiopterin + O2
?
worst substrate
-
-
?
L-tyrosine + 5,6,7,8-tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tyrosine + 6-methyltetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyl-4a-hydroxytetrahydrobiopterin
best substrate
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
L-tyrosine + tetrahydrobiopterin + O2
L-dopa + 4a-hydroxytetrahydrobiopterin + H2O
-
-
-
?
4-bromo-L-phenylalanine + 6-methyltetrahydropterin + O2
?
-
low activity
-
-
?
L-phenylalanine + tetrahydropteridine + 2 O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + 2 H2O
-
-
-
?
L-Tyr + DL-6-methyl-5,6,7,8-tetrahydropterin + O2
?
-
significant activity at a concetration of DL-6-methyl-5,6,7,8-tetrahydropterine: 1.5 mM
-
-
?
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin + O2
?
-
synthetic pterin as electron donor
-
-
?
L-tyrosine + 5,6,7,8-tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
3,4-dihydroxyphenylalanine + ?
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
?
-
-
-
-
?
L-tyrosine + 6-methyl-tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyl-4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tyrosine + 6-methyltetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyl-4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tyrosine + 6-methyltetrahydropterin + O2
?
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
L-tyrosine + tetrahydrobiopterin + O2
L-dopa + 4a-hydroxytetrahydrobiopterin + H2O
-
-
-
-
?
L-tyrosine + tetrahydropteridine + O2
3,4-dihydroxyphenylalanine + dihydropteridine + H2O
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
best substrate
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
recombinant wild-type and mutant
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + 2-amino-4-hydroxy-6-methyltetrahydropterin + O2
?
-
synthetic pterin as electron donor
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
-
684367, 685885, 685887, 687055, 687935, 688519, 688523, 688528, 688545, 688624, 689074, 689215, 689999, 690099, 695599, 697761, 713957, 714205, 714239
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
enzyme ativity regulation by endothelins is mediated by the NO pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
key enzyme in dopamine biosynthesis, the enzyme is involved in the survival of grafted embryonic dopamine neurons after transplantation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
key enzyme in dopamine biosynthesis, the majority of dopamine is derived from recycling after dopamine exocytosis, but loss in dopamine leads to de novo synthesis of dopamine, due to increased enzyme activity since the feedback enzyme inhibition by dopamine is reduced, regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
the enzyme catalyzes the rate-limiting step in dopamine biosynthesis, enzyme inhibition in the brain leads to hypothalamic reduced dopamine and DOPAC levels and increased pituitary prolactine, while the norepinephrine levels remain unaltered, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
the rate-limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of residue Ser40. Phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme, regulation mechanism overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
tyrosine hydroxylase is involved in dopamine biosynthesis and the rat nigrostriatal pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
rate-limiting step in catecholamine biosynthesis
-
-
?
additional information
?
-
-
4-substituted substrate analogues get hydroxylated at position 4 or 3, the latter is preferred with big-sized substituents, multiply hydroxylated products occur as well
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
neuronal activity, modulated e.g. by KCl, mediates changes in TH expression, overview
-
-
?
additional information
?
-
-
postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter, in vitro stimulation of sympathetic neurons increases tyrosine hydroxylase and norepinephrine synthesis to a greater extent than it stimulates norepinephrine reuptake and the NE transporter, overview
-
-
?
additional information
?
-
-
the enzyme is not circadianally regulated by the chromaffin cell clock, overview
-
-
?
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
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
best substrate
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
L-dopa + 4a-hydroxytetrahydrobiopterin + H2O
-
-
-
?
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
L-tyrosine + tetrahydrobiopterin + O2
L-dopa + 4a-hydroxytetrahydrobiopterin + H2O
-
-
-
-
?
L-tyrosine + tetrahydropteridine + O2
3,4-dihydroxyphenylalanine + dihydropteridine + H2O
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
enzyme ativity regulation by endothelins is mediated by the NO pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
key enzyme in dopamine biosynthesis, the enzyme is involved in the survival of grafted embryonic dopamine neurons after transplantation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
key enzyme in dopamine biosynthesis, the majority of dopamine is derived from recycling after dopamine exocytosis, but loss in dopamine leads to de novo synthesis of dopamine, due to increased enzyme activity since the feedback enzyme inhibition by dopamine is reduced, regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
the enzyme catalyzes the rate-limiting step in dopamine biosynthesis, enzyme inhibition in the brain leads to hypothalamic reduced dopamine and DOPAC levels and increased pituitary prolactine, while the norepinephrine levels remain unaltered, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
the rate-limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of residue Ser40. Phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme, regulation mechanism overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
tyrosine hydroxylase is involved in dopamine biosynthesis and the rat nigrostriatal pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
-
rate-limiting step in catecholamine biosynthesis
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
neuronal activity, modulated e.g. by KCl, mediates changes in TH expression, overview
-
-
?
additional information
?
-
-
postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter, in vitro stimulation of sympathetic neurons increases tyrosine hydroxylase and norepinephrine synthesis to a greater extent than it stimulates norepinephrine reuptake and the NE transporter, overview
-
-
?
additional information
?
-
-
the enzyme is not circadianally regulated by the chromaffin cell clock, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
tetrahydrobiopterin
-
-
657679, 684367, 685885, 685887, 687055, 687935, 688523, 688528, 688545, 688624, 689074, 689215, 689999, 690099, 695599, 697761, 698498, 701155, 726856, 728156
tetrahydrobiopterin
-
binding of dopamine to the high-affinity site of the enzyme 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
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Iron
phosphate
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-[(3-azido-6-nitrobenzylidene)amino]-2,6-diamino-4-pyrimidinone
-
competitive against tetrahydrobiopterin
alpha-methyl-L-tyrosine
-
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
-
effects of long-term modulation at different concentrations, overview
endothelin-2
-
effects of long-term modulation at different concentrations, overview
nociceptin/orphanin FQ-NOP receptor system
-
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
-
salsolinol
-
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
dopamine
-
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
L-Dopa
-
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
-
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
-
additional information
-
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
-
additional information
-
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
-
additional information
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Hsc70
Hsc70 physically and functionally interacts with TH to regulate the enzyme activity and synaptic vesicle targeting
-
7,12-dimethylbenz[a]anthracene
-
tyrosine hydroxylase activity increases in the rat heart treated with 7,12-dimethylbenz[a]anthracene
Dextran sulfate
-
activates the enzyme in the crude extract, less effective with the purified enzyme
-
endothelin-1
-
effects of long-term modulation at different concentrations, overview
endothelin-2
-
effects of long-term modulation at different concentrations, overview
L-Dopa
-
L-DOPA treatment (20-200 microM) increases the levels of dopamine by 226%-504% after 3-6 h of treatment and enhances the activities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase
RNA
-
below 0.015 mg/ml activation, rat brain enzyme contains RNA, about 10% of the total mass
heparin
-
activates the enzyme in the crude extract, less effective with the purified enzyme
additional information
-
long lasting induction of expression in anterior and posterior locus coelereus after injection of vindeburnol, i.e. RU24722, can be reversed by housing of the animals at 28°C
-
additional information
-
5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside activates the enzyme via AMP-activated protein kinase activation, AMP-activated protein kinase activates the enzyme by reversible phosphorylation at Ser19, Ser31, and Ser40
-
additional information
-
KCl induces the enzyme through activation of protein kinase C and protein kinase A, inhibition of induction by inhibitors H89 and SQ22536, but not by inhibitor PP2, overview
-
additional information
-
no activation by ETA and ETB selective agonists sarafotoxin S6b and IRL-1620, respectively
-
additional information
-
phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme, the low-affinity dopamine-binding site is able to regulate tyrosine hydroxylase activity in both the non-phosphorylated and pSer40 forms of the enzyme, with dissociation of dopamine from the site increasing activity 12fold and 9fold respectively
-
additional information
-
postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter, in vitro stimulation of sympathetic neurons increases tyrosine hydroxylase and norepinephrine synthesis to a greater extent than it stimulates norepinephrine reuptake and the NE transporter, overviewoverview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.033
6-Methyl-5,6,7,8-tetrahydropterin
recombinant wild-type, pH 7.1
0.055
6-Methyl-5,6,7,8-tetrahydropterin
recombinant wild-type, pH 6.0
0.059
6-Methyl-5,6,7,8-tetrahydropterin
recombinant mutant Y371F, pH 7.1
0.065
6-Methyl-5,6,7,8-tetrahydropterin
recombinant mutant Y371F, pH 6.0
0.0016
L-phenylalanine
mutant enzyme D425T, in 50 mM HEPES (pH 7.0), at 30°C
0.0053
L-phenylalanine
mutant enzyme D425G, in 50 mM HEPES (pH 7.0), at 30°C
0.0092
L-phenylalanine
mutant enzyme D425S, in 50 mM HEPES (pH 7.0), at 30°C
0.0105
L-phenylalanine
mutant enzyme D425Y, in 50 mM HEPES (pH 7.0), at 30°C
0.0144
L-phenylalanine
mutant enzyme D425F, in 50 mM HEPES (pH 7.0), at 30°C
0.0148
L-phenylalanine
mutant enzyme D425V, in 50 mM HEPES (pH 7.0), at 30°C
0.0152
L-phenylalanine
mutant enzyme D425C, in 50 mM HEPES (pH 7.0), at 30°C
0.0164
L-phenylalanine
mutant enzyme D425M, in 50 mM HEPES (pH 7.0), at 30°C
0.019
L-phenylalanine
mutant enzyme D425L, in 50 mM HEPES (pH 7.0), at 30°C
0.021
L-phenylalanine
mutant enzyme D425A, in 50 mM HEPES (pH 7.0), at 30°C
0.022
L-phenylalanine
mutant enzyme D425I, in 50 mM HEPES (pH 7.0), at 30°C
0.028
L-phenylalanine
mutant enzyme D425R, in 50 mM HEPES (pH 7.0), at 30°C
0.045
L-phenylalanine
mutant enzyme D425E, in 50 mM HEPES (pH 7.0), at 30°C
0.0565
L-phenylalanine
mutant enzyme D425Q, in 50 mM HEPES (pH 7.0), at 30°C
0.062
L-phenylalanine
mutant enzyme D425N, in 50 mM HEPES (pH 7.0), at 30°C
0.1
L-phenylalanine
wild type enzyme, in 50 mM HEPES (pH 7.0), at 30°C
0.2
L-phenylalanine
mutant enzyme D425K, in 50 mM HEPES (pH 7.0), at 30°C
5
L-phenylalanine
mutant enzyme D425H, in 50 mM HEPES (pH 7.0), at 30°C
0.00105
L-tyrosine
mutant enzyme D425T, in 50 mM HEPES (pH 7.0), at 30°C
0.006
L-tyrosine
mutant enzyme D425L, in 50 mM HEPES (pH 7.0), at 30°C
0.0069
L-tyrosine
mutant enzyme D425M, in 50 mM HEPES (pH 7.0), at 30°C
0.0089
L-tyrosine
mutant enzyme D425S, in 50 mM HEPES (pH 7.0), at 30°C
0.0106
L-tyrosine
mutant enzyme D425G, in 50 mM HEPES (pH 7.0), at 30°C
0.015
L-tyrosine
mutant enzyme D425C, in 50 mM HEPES (pH 7.0), at 30°C
0.0172
L-tyrosine
mutant enzyme D425F, in 50 mM HEPES (pH 7.0), at 30°C
0.0187
L-tyrosine
mutant enzyme D425H, in 50 mM HEPES (pH 7.0), at 30°C
0.03
L-tyrosine
mutant enzyme Y423A, in 50 mM HEPES (pH 7.0), at 30°C
0.0308
L-tyrosine
mutant enzyme D425Y, in 50 mM HEPES (pH 7.0), at 30°C
0.04
L-tyrosine
mutant enzyme D425V, in 50 mM HEPES (pH 7.0), at 30°C
0.041
L-tyrosine
mutant enzyme D425I, in 50 mM HEPES (pH 7.0), at 30°C
0.044
L-tyrosine
mutant enzyme Q424A, in 50 mM HEPES (pH 7.0), at 30°C
0.051
L-tyrosine
mutant enzyme T427A, in 50 mM HEPES (pH 7.0), at 30°C
0.056
L-tyrosine
mutant enzyme D425A, in 50 mM HEPES (pH 7.0), at 30°C
0.066
L-tyrosine
mutant enzyme Q426A, in 50 mM HEPES (pH 7.0), at 30°C
0.088
L-tyrosine
mutant enzyme D425R, in 50 mM HEPES (pH 7.0), at 30°C
0.097
L-tyrosine
mutant enzyme D425E, in 50 mM HEPES (pH 7.0), at 30°C
0.162
L-tyrosine
mutant enzyme D425Q, in 50 mM HEPES (pH 7.0), at 30°C
0.172
L-tyrosine
mutant enzyme D425N, in 50 mM HEPES (pH 7.0), at 30°C
2.39
L-tyrosine
mutant enzyme D425K, in 50 mM HEPES (pH 7.0), at 30°C
0.023
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S19E/S40E
0.028
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S8E
0.032
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S19A
0.033
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S19A
0.033
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S19E
0.034
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, wild-type enzyme
0.035
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S40A
0.035
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S40E
0.035
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S8E
0.036
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S8A
0.037
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S19E
0.037
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S19E/S40E
0.037
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S40E
0.039
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S8A
0.04
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, wild-type enzyme
0.045
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S40A
0.047
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S31E
0.048
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S31A
0.051
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S31A
0.051
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30°C, mutant enzyme S31E
0.005
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S31A, cosubstrate 0.3 mM tetrahydropterin
0.008
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S31E, cosubstrate 0.3 mM tetrahydropterin
0.009
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S19A, cosubstrate 0.3 mM tetrahydropterin
0.009
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S19E, cosubstrate 0.3 mM tetrahydropterin
0.009
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S19E/S40E, cosubstrate 0.3 mM tetrahydropterin
0.009
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S40E, cosubstrate 0.3 mM tetrahydropterin
0.009
L-tyrosine
-
pH 7.0, 30°C, wild-type enzyme, cosubstrate 0.3 mM tetrahydropterin
0.01
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S40A, cosubstrate 0.3 mM tetrahydropterin
0.011
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S8A, cosubstrate 0.3 mM tetrahydropterin
0.011
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S8E, cosubstrate 0.3 mM tetrahydropterin
0.026
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S19E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.035
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S19A, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.041
L-tyrosine
-
pH 7.0, 30°C, wild-type enzyme, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.042
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S8A, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.046
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S40A, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.047
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S40E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.047
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S8E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.053
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S31E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.055
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S31A, cosubstrate 0.4 mM 6-0.053 methyltetrahydropterin
0.059
L-tyrosine
-
pH 7.0, 30°C, mutant enzyme S19E/S40E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.055
tetrahydrobiopterin
-
W166F/W233F/W372F/F14W mutant protein, pH 7, 25°C
0.065
tetrahydrobiopterin
-
W166F/W233F/W372F/F74W mutant protein, pH 7, 25°C
0.077
tetrahydrobiopterin
-
W166F/W233F/W372F/F34W mutant protein, pH 7, 25°C
additional information
additional information
Km-values for tyrosine of mutant phenylalanine hydroxylase with tyrosine hydroxylation activity
-
additional information
additional information
-
phosphorylation converts the enzyme from a form possessing a high Km for pterin cofactor to a form with a low Km for pterin cofactor
-
additional information
additional information
-
rat brain: 2 kinetically distinguishable forms: low Km form, high Km form
-
additional information
additional information
-
rat brain: 2 kinetically distinguishable forms: low Km form, high Km form
-
additional information
additional information
-
kinetics analysis, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00368
-
activity of tyrosine hydroxylase, control level without treatment of L-DOPA in PC-12 cells
additional information
additional information
-
217% activity compared to control level, treatment with 0.02 mM L-DOPA in PC-12 cells at 6 h time point
additional information
-
232% activity compared to control level, treatment with 0.1 mM L-DOPA in PC-12 cells at 6 h time point
additional information
-
272% activity compared to control level, treatment with 0.02 mM L-DOPA in PC-12 cells at 6 h time point
additional information
-
55.2% activity compared to control level, treatment with 0.2 mM L-DOPA in PC-12 cells at 48 h time point
additional information
-
62.6% activity compared to control level, treatment with 0.2 mM L-DOPA in PC-12 cells at 1 h time point
additional information
-
68.2% activity compared to control level, treatment with 0.1 mM L-DOPA in PC-12 cells at 1 h time point
additional information
-
82.2% activity of tyrosine hydroxylase compared to control level, treatment with 0.02 mM L-DOPA in PC-12 cells at 1 h time point
additional information
-
82.3% activity compared to control level, treatment with 0.1 mM L-DOPA in PC-12 cells at 48 h time point
additional information
-
activity returns to the control level between 24-48 h after treatment with 0.02 mM L-DOPA.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 7.5
7.1
additional information
-
pH profile is affected by a variety of conditions: enzymatic phosphorylation by cAMP-dependent protein kinase, calmodulin-dependent protein kinase II and presence of polyanions
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 6.8
-
pH 5.0: less than 5% of maximal activity, pH 5.5-6.0: optimum, pH 6.8: about 30% of maximal activity, striatal homogenate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
developing, intereurons, the majority of cortical tyrosine hydroxylase cells at all ages contains phosphorylated tyrosine hydroxylase
-
neuropil, tyrosine hydroxylase-immunoreactive nerve terminals are distributed throughout the ganglia and contained exclusively pleomorphic clear synaptic vesicles
-
the paraventricular nucleus of the hypothalamus and the central amygdala
additional information
-
tyrosine hydroxylase in hypertensive rats shows 35% lower expression and a reduced Vmax due to a decreased phosphorylation at Ser40
-
2fold activity under cold stress. Injection of the angiotensin converting enzyme inhibitor enalapril malate prevented the increase of tyrosine hydroxylase under cold stress
-
-
-
increase in tyrosine hydroxylase protein levels and tyrosine hydroxylase enzyme activity might contribute to the enhanced noradrenergic activity in the heart in response to morphine withdrawam
-
2fold activity under cold stress. Injection of the angiotensin converting enzyme inhibitor enalapril malate prevented the increase of tyrosine hydroxylase under cold stress
-
2fold activity under cold stress. Injection of the angiotensin converting enzyme inhibitor enalapril malate prevented the increase of tyrosine hydroxylase under cold stress
-
treatment with the parasite-derived neurotrophic factor of Trypanosoma cruzi increased the number of tyrosine hydroxylase expressing neurons
-
interneurons in developing brain tissue, complete absence of cell death markers, i.e. active caspase 3, suggests that cortical tyrosine hydroxylase-immunoreactive neurons are not a transient population of cells, overview
-
myenteric, about 16% of the total number of axosomatic terminals show tyrosine hydroxylase immunoreactivity
-
olfactory and sensory neurons, cholinergic and adrenergic pathways modulate the proprotion of tyrosine hydroxylase-immunoreactive neurons, KCl induces the number of positive TH-IR neurons involving L-type Ca2+ channels, overview
-
3fold expression after treatment with the parasite-derived neurotrophic factor of Trypanosoma cruzi. The parasite-derived neurotrophic factor also promoted the phosphorylation-dependent activity of tyrosine hydroxylase
additional information
-
comparison of enzyme expressing cells of the diurnal rodent Arvicanthis niloticus with the enzyme of the nocturnal rodent Rattus norvegicus, no enzyme in cells of the basal forebrain, vasoactive intestinal polypeptide colocalizes with the enzyme, enzyme distribution, overview
additional information
-
cortical tyrosine hydroxylase neurons colocalizes with calretinin but not with parvalbumin or somatostatin
additional information
-
immunohistochemic analysis of enzyme content in neurons of wild-type and striatal 6-hydroxydopamine lesioned rats, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
molecules phosphorylated at their Ser31 and Ser40 are localized predominantly in the cytoplasm of PC-12D cells
-
molecules phosphorylated at Ser19 are found mainly in the nucleus
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
metabolism
-
tyrosine hydroxylase is the rate-limiting enzyme in catecholamine biosynthesis
metabolism
-
rate-limiting enzyme of catecholamine biosynthesis, regulated by phosphorylation, phosphorylation of Ser40 results in a decrease in affinity for catecholamines, phosphorylation of Ser31 results in a decrease in KM value for tetrahydrobiopterin, modified in the presence of NO, resulting in nitration of tyrosine residues (loss of activity) and the glutathionylation of cysteine residues
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). TY3H_RAT
498
0
55966
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
225000
-
pheochromocytoma tumors, asymmetric protein, native PAGE, gel filtration and sucrose density gradient centrifugation
260000
56000
-
4 * 56000, about, pheochromocytoma tumor, SDS-PAGE and amino acid sequence analysis
additional information
additional information
-
peripheral noradrenergic neurons in superior cervical ganglion: MW 130000 Da
additional information
-
high molecular weight of brain enzyme is partly due to association with RNA. This makes it difficult to decide whether tyrosine hydroxylase molecules of different structure are present in the various regions of the brain, cell bodies of noradrenergic neurons: MW 200000 Da, substancia nigra and caudate nucleus, dopaminergic neurons: MW 65000 Da
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
tetramer
-
4 * 56000, about, pheochromocytoma tumor, SDS-PAGE and amino acid sequence analysis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
phosphoprotein
phosphorylation at the Ser-31 site may regulate enzyme subcellular localization by enabling its transport along microtubules and is necessary for enzyme association with vesicles
phosphoprotein
-
phosphorylation occurs at S8, S19, S31 and S40. Neither cAMP-dependent protein kinase nor extracellular signal-regulated kinase 2 activity for phosphorylation of tyrosine hydroxylase is affected by pre-existing phosphorylations. Phosphorylation of S40 by cAMP-dependent protein kinase is inhibited by bound dopamine
phosphoprotein
-
AMP-activated protein kinase activates the enzyme by reversible phosphorylation at Ser19, Ser31, and Ser40, activated by 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside and inhibited by PD-098059, compound C and 5'-amino-5'-dAdo, PD-098059 specifically inhibits phosphorylation at Ser31 without affecting phosphorylation at Ser19 and Ser40
phosphoprotein
-
phosphorylation of Ser40 activtes the enzyme by reversing the inhibition by dopamine binding
phosphoprotein
-
reversible phosphorylation at Ser40 is required for enzyme activation, inhibited by the nociceptin/orphanin FQ-NOP receptor system, while phosphorylation on Ser31 is unaffected
phosphoprotein
-
the enzyme is phosphorylated at Ser19, Ser31, and Ser40, leading to its activation
phosphoprotein
-
the enzyme is regulated by phosphorylation of Ser19, Ser31, and Ser40, overview
phosphoprotein
-
enzyme molecules phosphorylated at their Ser31 and Ser40 are localized predominantly in the cytoplasm of PC12D cells. However, those molecules phosphorylated at Ser19 are found mainly in the nucleus, whereas they are negligible in the cytoplasm. The phosphorylation of the N-terminal portion regulates the degradation of this enzyme by the ubiquitin-proteasome pathway
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of the binary complex with iron and 7,8-dihydrobiopterin obtained by equilibrium dialysis, solutions degassed by helium and crystal growth in nitrogen atmosphere at 4°C
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A297L
the mutation mediates high affinity dopamine inhibition through Vmax reduction and increasing the Km value for the cofactor
D361N
the mutant shows increased Vmax compared to the wild type enzyme
D425A
the mutant shows strongly reduced activity compared to the wild type enzyme
D425C
the mutant shows strongly reduced activity compared to the wild type enzyme
D425E
the mutant shows strongly reduced activity compared to the wild type enzyme
D425F
the mutant shows strongly reduced activity compared to the wild type enzyme
D425G
the mutant shows strongly reduced activity compared to the wild type enzyme
D425H
the mutant shows strongly reduced activity compared to the wild type enzyme
D425I
the mutant shows strongly reduced activity compared to the wild type enzyme
D425K
the mutant shows strongly reduced activity compared to the wild type enzyme
D425L
the mutant shows strongly reduced activity compared to the wild type enzyme
D425M
the mutant shows strongly reduced activity compared to the wild type enzyme
D425N
the mutant shows strongly reduced activity compared to the wild type enzyme
D425Q
the mutant shows strongly reduced activity compared to the wild type enzyme
D425R
the mutant shows strongly reduced activity compared to the wild type enzyme
D425S
the mutant shows strongly reduced activity compared to the wild type enzyme
D425T
the mutant shows strongly reduced activity compared to the wild type enzyme
D425V
D425Y
the mutant shows strongly reduced activity compared to the wild type enzyme
E362Q
the mutant shows reduced Vmax compared to the wild type enzyme
E362R/E365R
the mutation mediates high affinity dopamine inhibition through Vmax reduction and increasing the Km value for the cofactor
E365Q
the mutant shows reduced Vmax compared to the wild type enzyme
H323Y
enhanced Km for tyrosine, 4.5fold enhanced phenylalanine hydroxylation activity, active site mutant
K366L
the mutant shows reduced Vmax compared to the wild type enzyme
Q310H
4fold reduced tyrosine hydroxylation/dopa formation activity, slightly enhanced phenylalanine hydroxylation activity, active site mutant
Q424A
the mutant shows reduced activity compared to the wild type enzyme
Q426A
the mutant strongly reduced activity compared to the wild type enzyme
R37E/R38E
the Km value for tetrahydrobiopterin measured for the mutant is approximately half that of the wild type enzyme
S368A
the mutation mediates high affinity dopamine inhibition through Vmax reduction and increasing the Km value for the cofactor
T427A
the mutant shows reduced activity compared to the wild type enzyme
Y371F
increased Km for tyrosine and pterin cosubstrates, highly decreased Km for phenylalanine
Y423A
the mutant shows reduced activity compared to the wild type enzyme
E332A
-
the E332A mutant hydroxylates less than 1% L-tyrosine compared to wild type and does not produce 4a-hydroxytetrahydrobiopterin
E376H
-
iron content is not significantly altered. Pterin oxidation at 1.2% of the wild-type activity. Tyrosine hydroxylation is less than 0.4% of the wild-type value
E376Q
-
iron content is not significantly altered. Pterin oxidation at 0.4% of the wild-type activity. Tyrosine hydroxylation is 0.39% of the wild-type value
H331E/E376H
-
mutant enzyme contains significantly less iron than the wild-type enzyme. Pterin oxidation at 0.21% of the wild-type activity. Tyrosine hydroxylation is less than 0.4% of the wild-type value
H331Q
-
mutant enzyme is not successfully expressed. Pterin oxidation at 2.4% of the wild-type activity. Tyrosine hydroxylation is less than 0.002% of the wild-type value
H336E
-
significant decrease in iron content. Pterin oxidation at 6.3% of the wild-type activity. Tyrosine hydroxylation is 0.78% of the wild-type value
H336Q
-
iron-free mutant enzyme. Pterin oxidation at 11.9% of the wild-type activity. Tyrosine hydroxylation is 3.7% of the wild-type value
S19E
S19E/S40E
S31E
S395A
-
the S395A mutant produces 4a-hydroxytetrahydrobiopterin at the same rate as wild type, but does so in predominantly uncoupled reaction (2% of wild type enzyme L-tyrosine hydroxylation)
S40E
S8E
W166F/W233F/W372F/F14W
-
introduced tryptophan residue in regulatory domain
W166F/W233F/W372F/F34W
-
introduced tryptophan residue in regulatory domain
W166F/W233F/W372F/F74W
-
introduced tryptophan residue in regulatory domain
additional information
D425V
335fold reduced tyrosine hydroxylation/dopa formation activity, 120fold reduced reaction velocity with tyrosine, 3fold enhanced phenylalanine hydroxylation activity, active site mutant
D425V
the mutant shows strongly reduced activity compared to the wild type enzyme
S19E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. Inactivated 1.8fold slower than the wild-type enzyme at 42°C in presence of 2% glycerol
S19E/S40E
-
investigation of regulation by phosphorylation, slight decrease in KM value for tetrahydrobiopterin, slight increase in Vmax value
S31E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. Inactivated 1.8fold slower than the wild-type enzyme at 42°C in presence of 2% glycerol
S40E
-
inactivated 1.6fold faster than the wild-type enzyme at 42°C in presence of 2% glycerol
S8E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. More stable than wild-type enzyme at 42°C in presence of 2% glycerol
additional information
active site mutants of phenylalanine hydroxylase lead to highly increased tyrosine hydroxylation activity of the enzyme mutants
additional information
-
investigation of the role of several amino acid residues in binding of substrate and ligands by site-specific mutagenesis
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
unstable in presence of phosphatidylinositol or NaCl at high concentration, but relatively stable in presence of heparin
45
-
in presence of 2% glycerol, enzymes lose activity in time-dependent manner
50
50
-
half-life of activated, phosphorylated enzyme: 5 min, half-life of nonphosphorylated enzyme: 15 min
50
-
in presence of 10% glycerol, all mutant enzymes are stable for at least 1 h
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 0.05% Tween 80, 0.1 mM EDTA, 25% glycerol, 5 mM sodium phosphate buffer, pH 7.5, 3 months without loss of activity
-
4°C, 5 h, without stabilizing agents, almost complete loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, Ni-NTA column chromatography, and Superdex 200 gel filtration
the phosphorylated TyrH is purified by Q-Sepharose column chromatography
2 kinetically distinguishable forms of the enzyme: low Km form and high Km form
-
heparin Sepharose chromatography, incubation with ferrous iron, Q-Sepharose chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli
expression in Spodoptera frugiperda cells via baculovirus expression system
-
expression of mutant enzymes H331E, H336Q, H336E, E376Q, E376H, H331E/E376H in Escherichia coli BL21
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme activity in the adrenal medulla, heart, and hypothalamus in Nomega-nitro-L-arginine methyl ester-treated rats is significantly increased compared to the control
heterogeneous nuclear ribonucleoprotein K is a transactivator of enzyme transcription
propolis, pollen, and caffeic acid phenethyl ester may mediate diminished enzyme activity in the heart, adrenal medulla, and hypothalamus in hypertensive rats
administration of silver nanoparticles to pregnant rats in a time- and dose-dependent manner increases the expression levels of the enzyme in the brain of male and female pups at all tested days after birth
-
atipamezole and/or levodopa treatments do not clearly affect on the amount of tyrosine hydroxylasein the striatum
-
compared with the control group, the expression of enzyme mRNA in both sides of the brain tissue in Parkinson rats decreases during 8 weeks, and the expression of mRNA in the injured brain tissue is significantly lower than that in normal rats
-
long-term stress from hypoxia leads to induction of tyrosine hydroxylase mRNA and protein in adrenal medulla and brain, this induction is usually associated with stimulation of tyrosine hydroxylase gene transcription rate. Tyrosine hydroxylase mRNA increases 8fold at 3 h after immobilization of rats and remains elevated about 2fold after 24 h. Tyrosine hydroxylase gene transcription increases in response to nicotine or stress. cAMP is a powerful inducer of both tyrosine hydroxylase mRNA and protein.
-
neither forskolin, nor phorbol esters or stimulatory agonists like glutamate, neurotensin, muscarine, nicotine or pituitary adenylate cyclase-activating peptide reproducibly induce tyrosine hydroxylase mRNA in the midbrain. When midbrain slices are treated with 1 mM 8-(4-chlorophenylthio)-cAMP or 0.01 mM forskolin, there is no induction of tyrosine hydroxylase mRNA.
-
single administration of vitamin C (0.5 mM) or co-administration of vitamin C with vitamin E (1 mM) for 72 h highly upregulates tyrosine hydroxylase expression, while single vitamin E treatment does not show any statistically significant effect
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
the enzyme is useful for determination of neuronal loss after brain treatment with neurotoxic compounds, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kaufman, S.
Aromatic amino acid hydroxylases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
18
217-282
1987
Bos taurus, Rattus norvegicus
-
Koizumi, S.; Matsushima, Y.; Nagatsu, T.; Linuma, H.; Takeuchi, T.; Umezawa, H.
3,4-Dihydroxystyrene, a novel microbial inhibitor for phenylalanine hydroxylase and other pteridine-dependent monooxygenases
Biochim. Biophys. Acta
789
111-118
1984
Rattus norvegicus
Nelson, T.J.; Kaufman, S.
Interaction of tyrosine hydroxylase with ribonucleic acid and purification with DNA-cellulose or poly(A)-sepharose affinity chromatography
Arch. Biochem. Biophys.
257
69-84
1987
Bos taurus, Rattus norvegicus
Fujisawa, H.; Okuno, S.
Tyrosine 3-monooxygenase from rat adrenals
Methods Enzymol.
142
63-71
1987
Rattus norvegicus
Grima, A.; Lamouroux, F.; Blanot, F.; Biguet, N.F.; Mallet, J.
Complete coding sequence of rat tyrosine hydroxylase mRNA
Proc. Natl. Acad. Sci. USA
82
617-621
1985
Rattus norvegicus
Tank, A.W.; Weiner, N.
Tyrosine 3-monooxygenase from rat pheochromocytoma
Methods Enzymol.
142
71-82
1987
Rattus norvegicus
Fitzpatrick, P.F.; Chlumsky, L.J.; Dauber, S.C.; O' Malley, K.L.
Expression of rat tyrosine hydroxylase in insect tissue culture cells and purification and characterization of the cloned enzyme
J. Biol. Chem.
265
2042-2047
1990
Rattus norvegicus
Richtand, N.M.; Inagami, T.; Misono, K.; Kuczenski, R.
Purification and characterization of rat striatal tyrosine hydroxylase. Comparison of the activation by cyclic AMP-dependent phosphorylation and by other effectors
J. Biol. Chem.
260
8465-8473
1985
Rattus norvegicus
Okuno, S.; Fujisawa, H.
Purification and some properties of tyrosine 3-monooxygenase from rat adrenal
Eur. J. Biochem.
122
49-55
1982
Rattus norvegicus
Goodwill, K.E.; Sabatier, C.; Stevens, R.C.
Crystal structure of tyrosine hydroxylase with bound cofactor analog and iron at 2.3.ANG. resolution: self-hydroxylation of Phe300 and the pterin-binding site
Biochemistry
37
13437-13445
1998
Rattus norvegicus
Hillas, P.J.; Fitzpatrick, P.F.
A mechanism for hydroxylation by tyrosine hydroxylase based on partitioning of substituted phenylalanines
Biochemistry
35
6969-6975
1996
Rattus norvegicus
Xu, Y.; Stokes, A.H.; Roskoski, R.Jr.; Vrana, K.E.
Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase
J. Neurosci. Res.
54
691-697
1998
Rattus norvegicus
Schmitt, P.; Reny-Palasse, V.; Bourde, O.; Garcia, C.; Pujol, J.F.
Further characterization of the long-term effect of RU24722 on tyrosine hydroxylase in the rat locus coeruleus
J. Neurochem.
61
1423-1429
1993
Rattus norvegicus
Haavik, J.
L-DOPA is a substrate for tyrosine hydroxylase
J. Neurochem.
69
1720-1728
1997
Bos taurus, Homo sapiens, Rattus norvegicus
Daubner, S.C.; Melendez, J.; Fitzpatrick, P.F.
Reversing the substrate specificities of phenylalanine and tyrosine hydroxylase: aspartate 425 of tyrosine hydroxylase is essential for L-DOPA formation
Biochemistry
39
9652-9661
2000
Rattus norvegicus (P04177)
Daubner, S.C.; Fitzpatrick, P.F.
Mutation to phenylalanine of tyrosine 371 in tyrosine hydroxylase increases the affinity for phenylalanine
Biochemistry
37
16440-16444
1998
Rattus norvegicus (P04177)
Royo, M.; Fitzpatrick, P.F.; Daubner, S.C.
Mutation of regulatory serines of rat tyrosine hydroxylase to glutamate: effects on enzyme stability and activity
Arch. Biochem. Biophys.
434
266-274
2005
Rattus norvegicus
Fitzpatrick, P.F.; Ralph, E.C.; Ellis, H.R.; Willmon, O.J.; Daubner, S.C.
Characterization of metal ligand mutants of tyrosine hydroxylase: insights into the plasticity of a 2-histidine-1-carboxylate triad
Biochemistry
42
2081-2088
2003
Rattus norvegicus
Gonzalez-Cuello, A.; Milanes, M.V.; Laorden, M.L.
Increase of tyrosine hydroxylase levels and activity during morphine withdrawal in the heart
Eur. J. Pharmacol.
506
119-128
2004
Rattus norvegicus
Khan, H.A.
Analytical characterization of a sensitive radioassay for tyrosine hydroxylase activity in rodent striatum
Neurochem. Res.
29
1467-1472
2004
Rattus norvegicus
Royo, M.; Colette Daubner, S.
Kinetics of regulatory serine variants of tyrosine hydroxylase with cyclic AMP-dependent protein kinase and extracellular signal-regulated protein kinase 2
Biochim. Biophys. Acta
1764
786-792
2006
Rattus norvegicus
Chuenkova, M.V.; Pereiraperrin, M.
Enhancement of tyrosine hydroxylase expression and activity by Trypanosoma cruzi parasite-derived neurotrophic factor
Brain Res.
1099
167-175
2006
Rattus norvegicus
Talas, Z.S.; Yurekli, M.
The effects of enalapril maleate and cold stress exposure on tyrosine hydroxylase activity in some rat tissues
Cell Biochem. Funct.
24
537-540
2006
Rattus norvegicus
Moura, E.; Pinho Costa, P.M.; Moura, D.; Guimaraes, S.; Vieira-Coelho, M.A.
Decreased tyrosine hydroxylase activity in the adrenals of spontaneously hypertensive rats
Life Sci.
76
2953-2964
2005
Rattus norvegicus
Patsenka, A.; Antkiewicz-Michaluk, L.
Inhibition of rodent brain monoamine oxidase and tyrosine hydroxylase by endogenous compounds - 1,2,3,4-tetrahydro-isoquinoline alkaloids
Pol. J. Pharmacol.
56
727-734
2005
Rattus norvegicus
Parrish, D.C.; Gritman, K.; Van Winkle, D.M.; Woodward, W.R.; Bader, M.; Habecker, B.A.
Postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter
Am. J. Physiol. Heart Circ. Physiol.
294
H99-H106
2008
Rattus norvegicus
Perfume, G.; Nabhen, S.L.; Riquelme Barrera, K.; Otero, M.G.; Bianciotti, L.G.; Vatta, M.S.
Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus
Am. J. Physiol. Regul. Integr. Comp. Physiol.
294
R905-R914
2008
Rattus norvegicus
Gomes, M.Z.; Raisman-Vozari, R.; Del Bel, E.A.
A nitric oxide synthase inhibitor decreases 6-hydroxydopamine effects on tyrosine hydroxylase and neuronal nitric oxide synthase in the rat nigrostriatal pathway
Brain Res.
1203
160-169
2008
Rattus norvegicus
Asmus, S.E.; Anderson, E.K.; Ball, M.W.; Barnes, B.A.; Bohnen, A.M.; Brown, A.M.; Hartley, L.J.; Lally, M.C.; Lundblad, T.M.; Martin, J.B.; Moss, B.D.; Phelps, K.D.; Phillips, L.R.; Quilligan, C.G.; Steed, R.B.; Terrell, S.L.; Warner, A.E.
Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex
Brain Res.
1222
95-105
2008
Rattus norvegicus
Lemos, D.R.; Goodspeed, L.; Tonelli, L.; Antoch, M.P.; Ojeda, S.R.; Urbanski, H.F.
Evidence for circadian regulation of activating transcription factor 5 but not tyrosine hydroxylase by the chromaffin cell clock
Endocrinology
148
5811-5821
2007
Rattus norvegicus
Bodnar, I.; Hechtl, D.; Szekacs, D.; Olah, M.; Nagy, G.M.
Effect of local (intracerebral and intracerebroventricular) administration of tyrosine hydroxylase inhibitor on the neuroendocrine dopaminergic neurons and prolactin release
Ideggyogy. Sz.
60
177-181
2007
Rattus norvegicus
Mahoney, M.M.; Ramanathan, C.; Smale, L.
Tyrosine hydroxylase positive neurons and their contacts with vasoactive intestinal polypeptide-containing fibers in the hypothalamus of the diurnal murid rodent, Arvicanthis niloticus
J. Chem. Neuroanat.
33
131-139
2007
Rattus norvegicus, Arvicanthis niloticus
Hayakawa, T.; Kuwahara, S.; Maeda, S.; Tanaka, K.; Seki, M.
Fine structural survey of tyrosine hydroxylase immunoreactive terminals in the myenteric ganglion of the rat duodenum
J. Chem. Neuroanat.
36
191-196
2008
Rattus norvegicus
Gordon, S.L.; Quinsey, N.S.; Dunkley, P.R.; Dickson, P.W.
Tyrosine hydroxylase activity is regulated by two distinct dopamine-binding sites
J. Neurochem.
106
1614-1623
2008
Rattus norvegicus
Olianas, M.C.; Dedoni, S.; Boi, M.; Onali, P.
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
J. Neurochem.
107
544-556
2008
Rattus norvegicus
Fukuda, T.; Ishii, K.; Nanmoku, T.; Isobe, K.; Kawakami, Y.; Takekoshi, K.
5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside stimulates tyrosine hydroxylase activity and catecholamine secretion by activation of AMP-activated protein kinase in PC12 cells
J. Neuroendocrinol.
19
621-631
2007
Rattus norvegicus
Terpstra, B.T.; Collier, T.J.; Marchionini, D.M.; Levine, N.D.; Paumier, K.L.; Sortwell, C.E.
Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons
J. Neurosci. Methods
166
13-19
2007
Rattus norvegicus
Chevalier, J.; Derkinderen, P.; Gomes, P.; Thinard, R.; Naveilhan, P.; Vanden Berghe, P.; Neunlist, M.
Activity-dependent regulation of tyrosine hydroxylase expression in the enteric nervous system
J. Physiol.
586
1963-1975
2008
Rattus norvegicus
Chen, X.; Xu, L.; Radcliffe, P.; Sun, B.; Tank, A.W.
Activation of tyrosine hydroxylase mRNA translation by cAMP in midbrain dopaminergic neurons
Mol. Pharmacol.
73
1816-1828
2008
Mus musculus, Rattus norvegicus
Zhang, Y.; Xu, H.; He, J.; Yan, B.; Jiang, W.; Li, X.; Li, X.M.
Quetiapine reverses altered locomotor activity and tyrosine hydroxylase immunoreactivity in rat caudate putamen following long-term haloperidol treatment
Neurosci. Lett.
420
66-71
2007
Rattus norvegicus
Perfume, G.; Morgazo, C.; Nabhen, S.; Batistone, A.; Hope, S.I.; Bianciotti, L.G.; Vatta, M.S.
Short-term regulation of tyrosine hydroxylase activity and expression by endothelin-1 and endothelin-3 in the rat posterior hypothalamus
Regul. Pept.
142
69-77
2007
Rattus norvegicus
Wallace, L.J.
A small dopamine permeability of storage vesicle membranes and end product inhibition of tyrosine hydroxylase are sufficient to explain changes occurring in dopamine synthesis and storage after inhibition of neuron firing
Synapse
61
715-723
2007
Rattus norvegicus
Jin, C.M.; Yang, Y.J.; Huang, H.S.; Lim, S.C.; Kai, M.; Lee, M.K.
Induction of dopamine biosynthesis by l-DOPA in PC12 cells: implications of L-DOPA influx and cyclic AMP
Eur. J. Pharmacol.
591
88-95
2008
Rattus norvegicus
Tank, A.W.; Xu, L.; Chen, X.; Radcliffe, P.; Sterling, C.R.
Post-transcriptional regulation of tyrosine hydroxylase expression in adrenal medulla and brain
Ann. N. Y. Acad. Sci.
1148
238-248
2008
Rattus norvegicus
Wang, S.; Sura, G.R.; Dangott, L.J.; Fitzpatrick, P.F.
Identification by hydrogen/deuterium exchange of structural changes in tyrosine hydroxylase associated with regulation
Biochemistry
48
4972-4979
2009
Rattus norvegicus (P04177)
Lehtonen, S.; Maennistoe, P.T.; Raasmaja, A.
Expression of tyrosine hydroxylase in the striatum of atipamezole-treated rats
Eur. J. Pharm. Sci.
36
602-604
2009
Rattus norvegicus
Chow, M.S.; Eser, B.E.; Wilson, S.A.; Hodgson, K.O.; Hedman, B.; Fitzpatrick, P.F.; Solomon, E.I.
Spectroscopy and kinetics of wild-type and mutant tyrosine hydroxylase: mechanistic insight into O2 activation
J. Am. Chem. Soc.
131
7685-7698
2009
Rattus norvegicus
James, P.; Rivier, C.; Lee, S.
Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer
J. Neuroendocrinol.
20
173-181
2008
Rattus norvegicus
Lee, H.Y.; Naha, N.; Ullah, N.; Jin, G.Z.; Kong, I.K.; Koh, P.O.; Seong, H.H.; Kim, M.O.
Effect of the co-administration of vitamin C and vitamin E on tyrosine hydroxylase and Nurr1 expression in the prenatal rat ventral mesencephalon
J. Vet. Med. Sci.
70
791-797
2008
Rattus norvegicus
Talas, Z.S.; Ozdemir, I.; Gok, Y.; Ates, B.; Yilmaz, I.
Role of selenium compounds on tyrosine hydroxylase activity, adrenomedullin and total RNA levels in hearts of rats
Regul. Pept.
159
137-141
2009
Rattus norvegicus
Daubner, S.C.; Le, T.; Wang, S.
Tyrosine hydroxylase and regulation of dopamine synthesis
Arch. Biochem. Biophys.
508
1-12
2011
Rattus norvegicus
Eser, B.; Fitzpatrick, P.
Measurement of intrinsic rate constants in the tyrosine hydroxylase reaction
Biochemistry
49
645-652
2010
Rattus norvegicus
Wang, S.; Lasagna, M.; Daubner, S.C.; Reinhart, G.D.; Fitzpatrick, P.F.
Fluorescence spectroscopy as a probe of the effect of phosphorylation at serine 40 of tyrosine hydroxylase on the conformation of its regulatory domain
Biochemistry
50
2364-2370
2011
Rattus norvegicus
Nakashima, A.; Mori, K.; Kaneko, Y.S.; Hayashi, N.; Nagatsu, T.; Ota, A.
Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme
Biochem. Biophys. Res. Commun.
407
343-347
2011
Rattus norvegicus
Daubner, S.C.; Avila, A.; Bailey, J.O.; Barrera, D.; Bermudez, J.Y.; Giles, D.H.; Khan, C.A.; Shaheen, N.; Thompson, J.W.; Vasquez, J.; Oxley, S.P.; Fitzpatrick, P.F.
Mutagenesis of a specificity-determining residue in tyrosine hydroxylase establishes that the enzyme is a robust phenylalanine hydroxylase but a fragile tyrosine hydroxylase
Biochemistry
52
1446-1455
2013
Rattus norvegicus (P04177)
Zhang, S.; Huang, T.; Ilangovan, U.; Hinck, A.P.; Fitzpatrick, P.F.
The solution structure of the regulatory domain of tyrosine hydroxylase
J. Mol. Biol.
426
1483-1497
2014
Rattus norvegicus
Fatemi Tabatabaie, S.R.; Mehdiabadi, B.; Mori Bakhtiari, N.; Tabandeh, M.R.
Silver nanoparticle exposure in pregnant rats increases gene expression of tyrosine hydroxylase and monoamine oxidase in offspring brain
Drug Chem. Toxicol.
40
440-447
2017
Rattus norvegicus
Chen, Y.; Lian, Y.; Ma, Y.; Wu, C.; Zheng, Y.; Xie, N.
The expression and significance of tyrosine hydroxylase in the brain tissue of Parkinsons disease rats
Exp. Ther. Med.
14
4813-4816
2017
Rattus norvegicus
Briggs, G.; Bulley, J.; Dickson, P.
Catalytic domain surface residues mediating catecholamine inhibition in tyrosine hydroxylase
J. Biochem.
155
183-193
2014
Rattus norvegicus (P04177)
Parra, L.A.; Baust, T.B.; Smith, A.D.; Jaumotte, J.D.; Zigmond, M.J.; Torres, S.; Leak, R.K.; Pino, J.A.; Torres, G.E.
The molecular chaperone Hsc70 interacts with tyrosine hydroxylase to regulate enzyme activity and synaptic vesicle localization
J. Biol. Chem.
291
17510-17522
2016
Rattus norvegicus (P04177), Mus musculus (P24529), Mus musculus
Jorge-Finnigan, A.; Kleppe, R.; Jung-Kc, K.; Ying, M.; Marie, M.; Rios-Mondragon, I.; Salvatore, M.F.; Saraste, J.; Martinez, A.
Phosphorylation at serine 31 targets tyrosine hydroxylase to vesicles for transport along microtubules
J. Biol. Chem.
292
14092-14107
2017
Homo sapiens, Rattus norvegicus (P04177)
Ekhteiari Salmas, R.; Durdagi, S.; Gulhan, M.F.; Duruyurek, M.; Abdullah, H.I.; Selamoglu, Z.
The effects of pollen, propolis, and caffeic acid phenethyl ester on tyrosine hydroxylase activity and total RNA levels in hypertensive rats caused by nitric oxide synthase inhibition experimental, docking and molecular dynamic studies
J. Biomol. Struct. Dyn.
36
609-620
2018
Rattus norvegicus (P04177)
Banerjee, K.; Wang, M.; Cai, E.; Fujiwara, N.; Baker, H.; Cave, J.W.
Regulation of tyrosine hydroxylase transcription by hnRNP K and DNA secondary structure
Nat. Commun.
5
5769
2014
Bos taurus, Danio rerio, Cavia porcellus, Felis catus, Gadus morhua, Gorilla gorilla, Oryzias latipes, Meleagris gallopavo, Takifugu rubripes, Taeniopygia guttata, Xenopus tropicalis, Pongo abelii, Tursiops truncatus, Gasterosteus aculeatus, Anolis carolinensis, Latimeria chalumnae, Rattus norvegicus (P04177), Homo sapiens (P07101), Mus musculus (P24529), Canis lupus familiaris (Q68CI2), Gallus gallus (Q9PU40)
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