Information on EC 1.14.16.2 - tyrosine 3-monooxygenase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
1.14.16.2
-
RECOMMENDED NAME
GeneOntology No.
tyrosine 3-monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
mechanism
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
mechanism
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
mechanism
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
stereochemical analysis of ligand binding
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
requires Fe2+, activated by phosphorylation, catalysed by EC 2.7.1.128 [acetyl-CoA carboxylase] kinase
-
-
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
ligand binding model, hTH1
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
H-NMR analysis of conformation of the complex between phenylalanine, 6-methyltetrahydropterin and isoform hTH1
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
active binding site
-
L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
secondary structure and conformation analysis of phosphorylated and unphosphorylated isoform hTH1, phosphorylation site of hTH1 is Ser-40
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidation
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
betalamic acid biosynthesis
-
-
catecholamine biosynthesis
-
-
catecholamine biosynthesis
-
-
Isoquinoline alkaloid biosynthesis
-
-
Metabolic pathways
-
-
rosmarinic acid biosynthesis II
-
-
Tyrosine metabolism
-
-
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-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAT-2
Caenorhabditis elegans N2 Bristol
-
-
-
hTH2
-
-
L-tyrosine hydroxylase
-
-
-
-
monophenol monooxygenase
-
-
oxygenase, tyrosine 3-mono-
-
-
-
-
TH1
-
isoform
TH1
-
isozyme
TH2
-
isoform
TyrH
P07101
-
TyrH
P04177
-
tyrosine 3-hydroxylase
-
-
-
-
tyrosine 3-monooxygenase
-
-
tyrosine hydroxylase
-
-
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
Caenorhabditis elegans N2 Bristol
-
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
Drosophila melanogaster Canton S
-
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
Drosophila virilis 101
-
-
-
tyrosine hydroxylase
GQ403009
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
GQ403014 and GQ403013 and GQ403012
-
tyrosine hydroxylase
P07101
-
tyrosine hydroxylase
GQ403011
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
Mus musculus C57BL/6J
-
-
-
tyrosine hydroxylase
GQ403010
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
P04177
-
tyrosine hydroxylase
-
-
tyrosine hydroxylase
A5YVV2
-
tyrosine hydroxylase
Tribolium castaneum GA-1
A5YVV2
-
-
tyrosine hydroxylase type 1
-
isoform
tyrosine-3-mono-oxygenase
-
-
tyrosine-3-mono-oxygenase
-
-
tyrosine-3-monooxygenase
-
-
CAS REGISTRY NUMBER
COMMENTARY
9036-22-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
the unstriped Nile grass rat, female animals
-
-
Manually annotated by BRENDA team
Caenorhabditis elegans N2 Bristol
-
-
-
Manually annotated by BRENDA team
strain Canton S
-
-
Manually annotated by BRENDA team
Drosophila melanogaster Canton S
strain Canton S
-
-
Manually annotated by BRENDA team
strain 101
-
-
Manually annotated by BRENDA team
Drosophila virilis 101
strain 101
-
-
Manually annotated by BRENDA team
-
GQ403009
GenBank
Manually annotated by BRENDA team
-
GQ403014 and GQ403013 and GQ403012
GenBank
Manually annotated by BRENDA team
4 isoforms hTH1, hTH2, hTH3, hTH4
-
-
Manually annotated by BRENDA team
isoform 1 hTH1
-
-
Manually annotated by BRENDA team
isozyme TH 1
-
-
Manually annotated by BRENDA team
isozyme TH-1 to TH-4
-
-
Manually annotated by BRENDA team
isozymes TH1 and TH4
-
-
Manually annotated by BRENDA team
-
GQ403011
GenBank
Manually annotated by BRENDA team
; alpha-synuclein knock-out mutant
-
-
Manually annotated by BRENDA team
C57BL/6J mice
-
-
Manually annotated by BRENDA team
male ASKO mice, strain B6:129X1-Snca
-
-
Manually annotated by BRENDA team
sepiapterin reductase-null mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
-
-
Manually annotated by BRENDA team
-
GQ403010
GenBank
Manually annotated by BRENDA team
ridibunda, frog; tyrosinase activity is modified to tyrosine hydroxylase activity via immobilization
-
-
Manually annotated by BRENDA team
male E14 Fisher 344 rats
-
-
Manually annotated by BRENDA team
male Sprague-Dawley albino rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
PC12 cells
-
-
Manually annotated by BRENDA team
pregnant Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rat, female animals
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
SpragueDawley rats
-
-
Manually annotated by BRENDA team
Tribolium castaneum GA-1
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
tyrosine hydroxylase is the rate-limiting enzyme in catecholamine biosynthesis
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
metabolism
-
the enzyme performs the rate-limiting step in catecholamine synthesis
metabolism
-
tyrosine hydroxylase is the key enzyme in the synthesis of dopamine
metabolism
Caenorhabditis elegans N2 Bristol
-
tyrosine hydroxylase is the key enzyme in the synthesis of dopamine
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,4-dihydroxy-L-phenylalanine + 6,7-dimethyltetrahydropteridine + O2
?
show the reaction diagram
-
i.e. L-dopa, L-dopa-oxidase activity
-
-
?
3,4-dihydroxy-L-phenylalanine + tetrahydropterin + O2
?
show the reaction diagram
-
i.e. L-dopa, 4 isoforms, thiols required, stimulation by Fe2+ and tetrahydropterin
-
-
?
4-bromo-L-phenylalanine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
low activity
-
-
?
4-chloro-L-phenylalanine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
4-fluoro-L-phenylalanine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
4-methoxy-L-phenylalanine + 6-methyltetrahydropteridine + O2
?
show the reaction diagram
-
-
-
-
?
4-methyl-L-phenylalanine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyltetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 3-hydroxyphenylalanine + dihydropteridine + H2O
show the reaction diagram
-
the enzyme prefers L-tyrosine as a substrate over L-phenylalanine by an order of magnitude
-
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
show the reaction diagram
-
recombinant wild-type and mutant
-
?
L-phenylalanine + tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-phenylalanine + tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
P04177
wild-type and mutants
-
?
L-tryptophan + 6-methyltetrahydrobiopterin + O2
?
show the reaction diagram
-
worst substrate
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
?
show the reaction diagram
-
the enzyme prefers L-tyrosine as a substrate over L-tryptophan by 25fold
-
-
?
L-Tyr + DL-6-methyl-5,6,7,8-tetrahydropterin + O2
?
show the reaction diagram
-
significant activity at a concetration of DL-6-methyl-5,6,7,8-tetrahydropterine: 1.5 mM
-
-
?
L-tyrosine + (6R)-5,6,7,8-tetrahydrobiopterin + O2
3,4-dihydroxyphenylalanine + ?
show the reaction diagram
-
-
-
-
?
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + (6R)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
recombinant hTH1
-
-
?
L-tyrosine + (6R)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
cosubstrate has a regulatory role for all 4 isoforms
-
-
?
L-tyrosine + (6R)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
preferred electron donor
-
-
?
L-tyrosine + (6R)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
tyrosine at 0.1 mM and O2 at 4.8% inhibit with (6R)-L-erythro-tetrahydrobiopterin as electron donor, depending on O2 and cofactor concentration
-
-
?
L-tyrosine + (6R)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
probable regulatory role of cosubstrate for all 4 isoforms
-
-
?
L-tyrosine + (6RS)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + (6S)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin + O2
?
show the reaction diagram
-
synthetic pterin as electron donor
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin + O2
?
show the reaction diagram
-
synthetic pterin as electron donor
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6-methyltetrahydropterin + O2
?
show the reaction diagram
-
synthetic pterin as electron donor
-
-
?
L-tyrosine + 2-amino-4-hydroxy-6-methyltetrahydropterin + O2
?
show the reaction diagram
-
synthetic pterin as electron donor
-
-
?
L-tyrosine + 2-methyl-4-oxo-5,6,7,8-tetrahydropterin + O2
?
show the reaction diagram
-
recombinant hTH1
-
-
?
L-tyrosine + 5,6,7,8,-tetrahydro-L-biopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydro-L-biopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 5,6,7,8-tetrahydro-L-biopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydro-L-biopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 5,6,7,8-tetrahydro-L-biopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydro-L-biopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 5,6,7,8-tetrahydro-L-biopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydro-L-biopterin
show the reaction diagram
Drosophila virilis, Drosophila melanogaster Canton S, Drosophila virilis 101
-
-
-
-
?
L-tyrosine + 5,6,7,8-tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 5,6,7,8-tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
3,4-dihydroxyphenylalanine + ?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
3,4-dihydroxyphenylalanine + ?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
3,4-dihydroxyphenylalanine + ?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine + O2
3,4-dihydroxy-L-phenylalanine + ?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyl-tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyltetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyltetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyltetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 6-methyldihydropteridine + H2O
show the reaction diagram
-
best substrate
-
-
?
L-tyrosine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
artificial cosubstrate
-
-
?
L-tyrosine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
higher activity than with tetrahydropterin
-
-
?
L-tyrosine + ascorbate + O2
3,4-dihydroxy-L-phenylalanine + dihydroascorbate + H2O
show the reaction diagram
-
-
-
?
L-tyrosine + DL-6-methyl-5,6,7,8-tetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
P04177
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
best substrate
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
tetrahydropterin absolutely required
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
recombinant hTH1
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
substrate inhibition occurs at 0.1 mM tyrosine or O2 with (6R)- and (6RS)-tetrahydrobiopterin
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
recombinant wild-type and mutant
3,4-dihydroxy-L-phenylalanine is identical with dopa
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
the enzyme prefers L-tyrosine as a substrate over L-phenylalanine by an order of magnitude and over L-tryptophan by 25fold
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans N2 Bristol
-
the enzyme shows high substrate specificity for L-tyrosine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine, reaction is coupled with ascorbate oxidation
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
rate-limiting step in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
rate-limiting step in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
rate-limiting step in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P07101
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
alpha-synuclein is a negative regulator of the enzyme and the dopamine biosynthesis pathway
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
enzyme ativity regulation by endothelins is mediated by the NO pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
key and rate-limiting enzyme in dopamine and other catecholamine biosynthesis, regulation, mechanisms, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
key enzyme in dopamine synthesis, negative catecholamine end-product regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in dopamine biosynthesis, regulation by reversible phosphorylation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase activity and dopamine biosynthesis are enhanced by down-regulation of alpha-synuclein. Loss of functional alpha-synuclein may result in increased dopamine levels in neurons that may lead to cell injury or even death and is involved in Parkinson's disease
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, enzyme defects are associated with L-DOPA responsive and non-responsive dystonia and infantile parkinsonism, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme of the catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme expression is increased in ataxic mice, Cdk5 activity cannot account for abnormal tyrosine hydroxylase expression in the cerebellum
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is a major producer of the DOPA required for both cuticle tanning and immune-associated melanization, overview
i.e. L-dopa
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the glial cell line-derived neurotrophic factor, GDNF, is involved in the regulation of tyrosine hydroxylase levels in the midbrain
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the rate-limiting enzyme in the biosynthesis of the catecholamines
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
tyrosine hydroxylase is involved in dopamine biosynthesis and the rat nigrostriatal pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
tyrosine hydroxylase is the rate limiting enzyme in catecholamine synthesis, and is involved in Parkinson's disease, enzyme inhibition by alpha-synuclein causes the dopaminergic phenotype, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
tyrosine hydroxylase is the rate-limiting enzyme in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Mus musculus C57BL/6J
-
rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase activity and dopamine biosynthesis are enhanced by down-regulation of alpha-synuclein. Loss of functional alpha-synuclein may result in increased dopamine levels in neurons that may lead to cell injury or even death and is involved in Parkinson's disease
-
-
?
L-tyrosine + tetrahydrofolic acid + O2
?
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydropteridine + O2
3,4-dihydroxyphenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
tyramine + tetrahydrobiopterin + O2
dopamine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
active with diverse tetrahydropterin analogues, substituted at C6, C7 or C3, overview
-
-
-
additional information
?
-
-
tyrosinase activity is modified to tyrosine hydroxylase activity via immobilization
-
-
-
additional information
?
-
-
under aerobic conditions can generate significant amounts of reactive oxygen species, including hydrogen peroxide and hydroxyl radicals
-
-
-
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
?
-
-
circulating titer of estradiol-17 beta can act differentially on the enzyme to alter catecholamineergic activity. Estradiol-17 beta may participate in the acute regulation of the enzyme by interacting with the cAMP signaling pathway
-
-
-
additional information
?
-
-
direct function for tyrosine hydroxylase in the melanosome via a cencerted action with tyrosinase to promote pigmentation
-
-
-
additional information
?
-
-
key enzyme in dopamine biosynthesis, key enzyme in dopamine biosynthesis. Tissue-specific expression of the isoenzymes generated through alternative splicing of the tyrosine hydroxylase gene is a vital step in Drosophila development
-
-
-
additional information
?
-
-
the brain enzyme is sensitive to the thyroid status. Hormone excess activates and deficiency retards the enzyme activity by midifying its kinetic function
-
-
-
additional information
?
-
-
the enzyme catalyzes the rate-limiting step in the biosynthesis of dopmaine. The physiological effects of the mutations described in cases of autosomal recessive DOPA-responsive dystonia are primarily due to the decreased stability of the mutant proteins razher than decreases in their intrinsic activities
-
-
-
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
?
-
-
in nocturnal species, rhythms in tyrosine hydroxylase-containing neurons in the hypothalamus appear to be responsible for rhythms in prolactin secretion, 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
-
-
-
additional information
?
-
-
tyrosine hydroxylase stimulates GTP cyclohydrolase I activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + (6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin + O2
?
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + (6R)-L-erythro-tetrahydrobiopterin + O2
?
show the reaction diagram
-
probable regulatory role of cosubstrate for all 4 isoforms
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
best substrate
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
the enzyme prefers L-tyrosine as a substrate over L-phenylalanine by an order of magnitude and over L-tryptophan by 25fold
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
-
the enzyme shows high substrate specificity for L-tyrosine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
first step in biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine, reaction is coupled with ascorbate oxidation
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
rate-limiting step in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
rate-limiting step in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydrobiopterin + H2O
show the reaction diagram
-
rate-limiting step in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
alpha-synuclein is a negative regulator of the enzyme and the dopamine biosynthesis pathway
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
enzyme ativity regulation by endothelins is mediated by the NO pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
key and rate-limiting enzyme in dopamine and other catecholamine biosynthesis, regulation, mechanisms, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
key enzyme in dopamine synthesis, negative catecholamine end-product regulation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in dopamine biosynthesis, regulation by reversible phosphorylation, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase activity and dopamine biosynthesis are enhanced by down-regulation of alpha-synuclein. Loss of functional alpha-synuclein may result in increased dopamine levels in neurons that may lead to cell injury or even death and is involved in Parkinson's disease
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, enzyme defects are associated with L-DOPA responsive and non-responsive dystonia and infantile parkinsonism, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme of the catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme expression is increased in ataxic mice, Cdk5 activity cannot account for abnormal tyrosine hydroxylase expression in the cerebellum
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is a major producer of the DOPA required for both cuticle tanning and immune-associated melanization, overview
i.e. L-dopa
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the glial cell line-derived neurotrophic factor, GDNF, is involved in the regulation of tyrosine hydroxylase levels in the midbrain
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the rate-limiting enzyme in the biosynthesis of the catecholamines
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
tyrosine hydroxylase is involved in dopamine biosynthesis and the rat nigrostriatal pathway, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
tyrosine hydroxylase is the rate limiting enzyme in catecholamine synthesis, and is involved in Parkinson's disease, enzyme inhibition by alpha-synuclein causes the dopaminergic phenotype, overview
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
tyrosine hydroxylase is the rate-limiting enzyme in catecholamine biosynthesis
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O
show the reaction diagram
Caenorhabditis elegans N2 Bristol
-
the enzyme shows high substrate specificity for L-tyrosine
-
-
?
L-tyrosine + tetrahydrobiopterin + O2
3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Mus musculus C57BL/6J
-
rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase activity and dopamine biosynthesis are enhanced by down-regulation of alpha-synuclein. Loss of functional alpha-synuclein may result in increased dopamine levels in neurons that may lead to cell injury or even death and is involved in Parkinson's disease
-
-
?
L-tyrosine + tetrahydropteridine + O2
3,4-dihydroxyphenylalanine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
circulating titer of estradiol-17 beta can act differentially on the enzyme to alter catecholamineergic activity. Estradiol-17 beta may participate in the acute regulation of the enzyme by interacting with the cAMP signaling pathway
-
-
-
additional information
?
-
-
direct function for tyrosine hydroxylase in the melanosome via a cencerted action with tyrosinase to promote pigmentation
-
-
-
additional information
?
-
-
key enzyme in dopamine biosynthesis, key enzyme in dopamine biosynthesis. Tissue-specific expression of the isoenzymes generated through alternative splicing of the tyrosine hydroxylase gene is a vital step in Drosophila development
-
-
-
additional information
?
-
-
the brain enzyme is sensitive to the thyroid status. Hormone excess activates and deficiency retards the enzyme activity by midifying its kinetic function
-
-
-
additional information
?
-
-
the enzyme catalyzes the rate-limiting step in the biosynthesis of dopmaine. The physiological effects of the mutations described in cases of autosomal recessive DOPA-responsive dystonia are primarily due to the decreased stability of the mutant proteins razher than decreases in their intrinsic activities
-
-
-
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
?
-
-
in nocturnal species, rhythms in tyrosine hydroxylase-containing neurons in the hypothalamus appear to be responsible for rhythms in prolactin secretion, 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
-
-
-
additional information
?
-
-
tyrosine hydroxylase stimulates GTP cyclohydrolase I activity
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(6R)-5,6,7,8-tetrahydrobiopterin
-
-
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
i.e. BH4, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, competitive inhibition
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
-
5,6,7,8-tetrahydro-L-biopterin
-
-
5,6,7,8-tetrahydro-L-biopterin
-
-
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
strictly requirred
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine
-
-
6-Methyl-5,6,7,8-tetrahydropterin
-
-
6-methyl-tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
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
tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
6-methyltetrahydrobiopterin
-
-
additional information
-
a non-heme iron enzyme
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
activates the enzyme via retinol induction of extracellular Ca2+ influx, the activation is completely blocked by EGTA
Cu2+
-
slightly activating
Fe2+
-
activating
Fe2+
-
localized at the active site, the ferric is the inactive state, modelling of catecholamine and 6,7-dihydroxylated tetrahydroisoquinoline inhibitor docking to the active site Fe2+, overview
Fe2+
-
required for activity
Fe2+
-
-
Fe2+
-
activates
Iron
-
0.66 mol per mol of subunit; high spin Fe(III) in an environment of nearly axial symmetry
Iron
-
0.1 atom per subunit
Iron
-
0.5-0.75 mol of iron per mol of enzyme
Iron
-
incorporation of stoichiometric amounts of Fe2+ leads to 40fold increase in activity
Iron
-
required
Iron
-
Fe2+ activates
Iron
-
Fe2+ activates; required
Iron
-
-
Iron
-
Fe2+ activates
Mn2+
-
activates
NaCl
-
activates
phosphate
-
-
phosphate
-
activated enzyme contains: 0.75 mol per mol of subunit
phosphate
-
0.62 mol per mol of subunit
phosphate
-
1 covalently bound residue per subunit
phosphate
-
1 mol per mol of subunit
Zn2+
-
0.13 mol per mol of subunit
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(6R)-L-erythro-1',2'-dihydroxypropyltetrahydropterin
-
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
-
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
-
80% inhibition when the enzyme is preincubated with (6S)-L-erythro-1',2'-dihydroxypropyltetrahydropterin
1,10-phenanthroline
-
-
1,10-phenanthroline
-
complete
1,2,3,4-tetrahydropapaveroline
-
50% inhibition at 7.5 microM
2,2'-dipyridyl
-
-
2,4-diamino-6-dihydroxypropyl-5,6,7,8-tetrahydropterin
-
competitive against (6R)-L-erythro-tetrahydrobiopterin
2-hydroxyestradiol-17beta
-
noncompetitive
2-methyl-L-tyrosine
-
-
3,4-dihydroxy-L-phenylalanine
-
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-dihydroxy-L-phenylalanine
-
product inhibition
3,4-dihydroxybenzoic acid
-
-
3,4-dihydroxyphenylacetaldehyde
-
potent inhibitor, 0.01 and 0.02 mM cause 66% and 75% inhibition, respectively
3,4-dihydroxyphenylacetaldehyde
-
potent inhibitor
3,4-Dihydroxystyrene
-
-
3-iodo-L-tyrosine
-
-
3-iodo-L-tyrosine
-
complete
3-iodo-L-tyrosine
-
competitive inhibitor
3-iodotyrosine
-
-
5(N-phenylthiocarbamoyl)-5,6,7,8-tetrahydropterin
-
-
5-Deaza-6-methyltetrahydropterin
-
-
5-methyl-5,6,7,8-tetrahydropterin
-
competitive against (6R)-L-erythro-tetrahydrobiopterin
5-[(3-azido-6-nitrobenzylidene)amino]-2,6-diamino-4-pyrimidinone
-
competitive against tetrahydrobiopterin
6-methyltetrahydropterin
-
80% inhibition when the enzyme is preincubated with 6-methyltetrahydropterin
6-[2-(4-benzoylphenyl)propionyloxymethyl]-5,6,7,8-tetrahydropterin
-
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
-
competitive against (6R)-L-erythro-tetrahydrobiopterin
8-methyl-6,7-dimethyl-5,6,7,8-tetrahydropterin
-
competitive against (6R)-L-erythro-tetrahydrobiopterin
adrenalin
-
competitive
adrenaline
-
-
adrenaline
-
-
alpha-methyl-4-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
-
alpha-methyl-p-tyrosine
-
-
alpha-methyl-p-tyrosine
-
complete inhibition at 0.001 mM
alpha-Propyldihydroxyphenylacetamide
-
-
Ba2+
-
weak inhibition
Bathocuproine sulfonate
-
slightly
bathophenanthroline sulfonate
-
-
bathophenanthroline sulfonate
-
-
Catecholamines
-
-
Catecholamines
-
-
Catecholamines
-
feedback inhibition, reversible by phosphorylation
Catecholamines
-
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
Co2+
-
-
Co2+
-
competitive against Fe2+
Co2+
-
80% inhibition at 0.1 mM
CoCl2
-
0.1 mM CoCl2 results in more than 80% inhibition
dihydrobiopterin
-
L-dopa-oxidase activity
DL-6-methyl-5,6,7,8-tetrahydropterine
-
3.0-4.5 mM
dopamine
-
-
dopamine
-
competitive
dopamine
-
binds to the iron ion at the active site
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
dopamine
-
feedback inhibitor and catecholamine product, binding inhibits and stabilizes the enzyme, reversible and competitive inhibition with respect to tetrahydrobiopterin
dopamine
-
end product inhibition
dopamine
-
feedback inhibition, in the presence of 0.02 mM dopamine tyrosine hydroxylase enzyme specific activity is reduced by about 60%
dopamine
-
feedback inhibitor, competitively with tetrahydrobiopterin
dopamine quinone
-
covalent modification and inactivation
DTT
-
inactivates the enzyme, synergistically with tetrahydrobiopterin
endothelin-1
-
effects of long-term modulation at different concentrations, overview
endothelin-2
-
effects of long-term modulation at different concentrations, overview
epinephrine
-
-
epinephrine
-
feedback inhibitor
estradiol-17beta
-
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
-
inhibiting at concetration above 0.5 mM. adenosine 3',5' cyclic monophosphate enhances the inhibition at high estradiol-17beta concentrations
Fe3+
-
-
guanidine hydrochloride
-
no activity at guanidine hydrochloride concentrations exceeding 0.6 M
L-Dopa
-
modest feedback inhibition
L-Dopa
-
above 0.15 mM inhibiting L-dopa-oxidase activity in presence of tetrahydropterin, but not with 6,7-dimethyltetrahydropterin
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.
L-erythro-7,8-dihydrobiopterin
-
competitive against tetrahydropterin
L-phenylalanine
-
-
L-phenylalanine
-
-
L-tyrosine
-
-
L-tyrosine
-
substrate inhibition at concentrations above 0.05 mM
Methylcatechol
-
-
N-methyl-norsalsolinol
-
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
N-methyl-salsolinol
-
-
Ni2+
-
-
Ni2+
-
competitive against Fe2+
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
-
Noradrenalin
-
competitive
noradrenaline
-
-
noradrenaline
-
-
noradrenaline
-
-
norepinephrine
-
-
norepinephrine
-
-
norepinephrine
-
-
norepinephrine
-
feedback inhibitor
norsalsolinol
-
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
O2
-
above 4.8%
phenylalanine
-
L-isomer, not D-isomer
phenylalanine
-
-
RNA
-
above 0.015 mg/ml
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
tetrahydrobiopterin
-
substrate inhibition at tyrosine and O2 concentrations higher than 0.1 mM and 2.2 mM, respectively
tyrosine
-
0.1 mM
tyrosine
-
substrate inhibition, with (6R)-L-erythro-tetrahydrobiopterin
tyrosine
-
at concentrations above 0.03 mM
Zn2+
-
-
Zn2+
-
competitive against Fe2+
Mn2+
-
50% inhibition at 0.01 mM
additional information
-
pH-dependence of inhibitor binding
-
additional information
-
inhibited by metal chelating agents
-
additional information
-
inhibition of cAMP-protein kinase A and protein kinase C in crude extracts significantly reduces tyrosine hydroxylase activity
-
additional information
-
no inhibition by nonhydroxylated N-methyl-1,2,3,4-tetrahydroisoquinoline
-
additional information
-
glial cell line-derived neurotrophic factor, GDNF, supresses the enzyme expression in the midbrain
-
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
-
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
-
additional information
-
alpha-synuclein inhibits phosphorylation of the enzyme at Ser40 and enzyme activity, thereby regulating the dopamine level
-
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
-
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
-
additional information
-
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
-
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
-
UO126 significantly inhibits the basal phosphorylation of Ser40 in isoform TH1, but does not inhibit the phosphorylation of Ser44 in isoform TH2
-
additional information
-
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
-
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
1,4-dithiothreitol
-
48% activity without dithiotreitol
1-methyl-3-isobutylxanthine
-
1.5 mM
20-hydroxyecdysone
-
20-hydroxyecdysone feeding (0.06 mg) leads to a substantial rise in tyrosine hydroxylase activity
7,12-dimethylbenz[a]anthracene
-
tyrosine hydroxylase activity increases in the rat heart treated with 7,12-dimethylbenz[a]anthracene
8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate
-
i.e. 8-CPTcAMP, tyrosine hydroxylase protein level and activity rate are increased in MN9D cells in response to treatment with 8-CPTcAMP, mechanism, overview
adenosine 3',5' cyclic monophosphate
-
1 mM
bathocuproine sulfate
-
slight activation
-
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
estradiol-17beta
-
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
-
activating at concetration below 0.5 mM
forskolin
-
i.e. 8-CPTcAMP, tyrosine hydroxylase protein level and activity rate are increased in MN9D cells in response to treatment with 8-CPTcAMP, mechanism, overview
forskolin
-
forskolin selectively increases the phosphorylation of tyrosine hydroxylase at Ser40 by 1.8fold without increasing total tyrosine hydroxylase protein levels
GTP cyclohydrolase I
-
as concentrations of 5,6,7,8-tetrahydrobiopterin are increased (0.025 and 0.1 mM), the specific activity of tyrosine hydroxylase is stimulated in the presence of GTP cyclohydrolase I isoform C
-
heparin
-
0.1 mg/ml, activates
heparin
-
activates the enzyme in the crude extract, less effective with the purified enzyme
juvenile hormone-III
-
0.0001 or 0.0002 mg juvenile hormone-III application leads to a substantial rise in tyrosine hydroxylase activity
phosphatidyl-L-serine
-
activates
phosphatidyl-L-serine
-
no stimulation
phosphatidylinositol
-
0.1 mg/ml activates
phosphatidylinositol
-
no stimulation
Phospholipid
-
activates
Phospholipid
-
no stimulation
retinol
-
retinol activates tyrosine hydroxylase in vivo via two sequential non-genomic mechanisms: 1. retinol induces an influx in extracellular calcium, activation of protein kinase C and Ser40 phosphorylation, leading to tyrosine hydroxylase activation within 15 min, 2. the retinol-induced rise in intracellular calcium leads to an increase in reactive oxygen species, activation of extracellular signal-regulated kinase 1/2 and Ser31 phosphorylation and the maintenance of tyrosine hydroxylase activation for up to 2 h
RNA
-
below 0.015 mg/ml activation, rat brain enzyme contains RNA, about 10% of the total mass
SDS
-
0.01%, activates
theophylline
-
1.5 mM
thiols
-
activate the L-dopa activity
thyroxine
-
stimulatory effect is due to increased affinity of the enzyme for its cofactor 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine
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
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 28C
-
additional information
-
activation by phosphorylation
-
additional information
-
activation by phosphorylation; inhibitory effect of several compounds on L-dopa-oxidase activity
-
additional information
-
activation by phosphorylation
-
additional information
-
activation by phosphorylation
-
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
-
additional information
-
amphetamines upregulate the enzymein the central nervous system and the olfactory tubercle, overview
-
additional information
-
ethanol induces the enzyme activation of the cAMP/cyclic AMP-dependent protein kinase A pathway, the activation is reversible by ibogaine via glial cell line-derived neurotrophic factor, GNDF. Ethanol treatment results in an increase in tyrosine hydroxylase association with the chaperone heat shock protein that is mediated by the cAMP/PKA pathway and inhibited by GDNF, overview
-
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
-
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
-
phosphorylation at Ser40 activates the enzyme
-
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
-
cyclin-dependent kinase 5 phosphorylates tyrosine hydroxylase, but does not induce the enzyme expression
-
additional information
-
phosphorylation at Ser40 activates the enzyme, inhibition of alpha-synuclein, inhibiting enzyme phosphorylation, increases the enzyme activity
-
additional information
-
phosphorylation at Ser40 in the regulatory domain activates the enzyme, the activation is inhibited by alpha-synuclein
-
additional information
-
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
-
additional information
-
no activation by ETA and ETB selective agonists sarafotoxin S6b and IRL-1620, respectively
-
additional information
-
50 ng/ml epidermal growth factor significantly increases the phosphorylation of Ser31 in isoform TH1, while no phosphorylation of Ser35 in isoform TH2 is detected, stimulation with epidermal growth factor does not result in any changes in the phosphorylation of Ser40/44 or Ser19 or TH protein levels; muscarine significantly increases the phosphorylation of Ser40/44 and induces a substantial increase in the phosphorylation of Ser19 in both isoform TH1 and TH2 cells; stimulation with 0.01 mM forskolin significantly increases the phosphorylation of Ser40/44 in both isoform TH1 and TH2 cells. There is no significant difference in the level of forskolin-induced phosphorylation of Ser40/44 between isoform TH1 and TH2 cells. Ser31 phosphorylation levels are unchanged in isoform TH1, and phosphorylation of Ser35 is not detectable in isoform TH2 in either the control or stimulated cells, forskolin does not change Ser19 phosphorylation or total tyrosine hydroxylase protein levels in either cell type
-
additional information
-
10 ng/ml interleukin-1beta induces the phosphorylation of tyrosine hydroxylase at Ser40 1.4fold, 0.0001 mM forskolin induces a 1.5fold increase on tyrosine hydroxylase phosphorylation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.023
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S19E/S40E
0.028
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S8E
0.032
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S19A
0.033
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S19A; pH 7.0, 30C, mutant enzyme S19E
0.034
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, wild-type enzyme
0.035
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S40A; pH 7.0, 30C, mutant enzyme S40E; pH 7.0, 30C, mutant enzyme S8E
0.036
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S8A
0.037
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S19E; pH 7.0, 30C, mutant enzyme S19E/S40E; pH 7.0, 30C, mutant enzyme S40E
0.039
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S8A
0.04
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, wild-type enzyme
0.045
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S40A
0.047
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S31E
0.048
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S31A
0.051
(RS)-6-methyl-5,6,7,8-tetrahydropterin
-
pH 7.0, 30C, mutant enzyme S31A; pH 7.0, 30C, mutant enzyme S31E
0.058
2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine
-
-
-
0.0001
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
telencephalon extract, 10 microM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00015
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
telencephalon extract, 1 microM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.0002
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 10 microM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C; telencephalon extract, 1 nM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00022
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 1 nM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00024
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 1 microM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C; telencephalon extract, 1 fM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00026
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 1 fM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00034
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00035
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
telencephalon extract, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00045
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 0.01 mM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00048
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
telencephalon extract, 0.01 mM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00054
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
telencephalon extract, 1 mM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.00058
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
hypothalamus extract, 1 mM estadriol-17beta, 0.1-0.5 mM L-tyrosine, 1-8 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, PBS buffer pH 6.2, 2-mercaptoethanol, catalase, 30C
0.045
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine
-
0.1 mM L-tyrosine, 0.1 mg/ml catalase, 50 mM HEPES pH 7.0, 0.01 mM ferrous ammonium sulfate, 1 mM dithiothreitol, 25C
0.34
6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine
-
30C
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
0.06 - 0.1
6-Methyl-5,6,7,8-tetrahydropterin
-
-
0.065
6-Methyl-5,6,7,8-tetrahydropterin
-
recombinant mutant Y371F, pH 6.0
0.15
6-Methyl-5,6,7,8-tetrahydropterin
-
-
0.95
6-Methyl-5,6,7,8-tetrahydropterin
-
-
0.051
6-methyltetrahydropterin
-
pH 7.1, 25C, wild-type enzyme
0.19
6-methyltetrahydropterin
-
pH 7.1, 25C, mutant enzyme H336E
0.339
6-methyltetrahydropterin
-
pH 7.1, 25C, mutant enzyme H331E
0.409
6-methyltetrahydropterin
-
pH 7.1, 25C, mutant enzyme H336Q
0.056
L-Dopa
-
recombinant hTH1, dopa-oxidase activity with tetrahydropterin
0.146
L-Dopa
-
recombinant, dopa-oxidase activity with 6,7-dimethyltetrahydropterin
0.0016
L-phenylalanine
-
mutant enzyme D425T, in 50 mM HEPES (pH 7.0), at 30C
0.0053
L-phenylalanine
-
mutant enzyme D425G, in 50 mM HEPES (pH 7.0), at 30C
0.0092
L-phenylalanine
-
mutant enzyme D425S, in 50 mM HEPES (pH 7.0), at 30C
0.0105
L-phenylalanine
-
mutant enzyme D425Y, in 50 mM HEPES (pH 7.0), at 30C
0.0144
L-phenylalanine
-
mutant enzyme D425F, in 50 mM HEPES (pH 7.0), at 30C
0.0148
L-phenylalanine
-
mutant enzyme D425V, in 50 mM HEPES (pH 7.0), at 30C
0.0152
L-phenylalanine
-
mutant enzyme D425C, in 50 mM HEPES (pH 7.0), at 30C
0.0164
L-phenylalanine
-
mutant enzyme D425M, in 50 mM HEPES (pH 7.0), at 30C
0.019
L-phenylalanine
-
mutant enzyme D425L, in 50 mM HEPES (pH 7.0), at 30C
0.021
L-phenylalanine
-
mutant enzyme D425A, in 50 mM HEPES (pH 7.0), at 30C
0.022
L-phenylalanine
-
mutant enzyme D425I, in 50 mM HEPES (pH 7.0), at 30C
0.028
L-phenylalanine
-
mutant enzyme D425R, in 50 mM HEPES (pH 7.0), at 30C
0.045
L-phenylalanine
-
mutant enzyme D425E, in 50 mM HEPES (pH 7.0), at 30C
0.0565
L-phenylalanine
-
mutant enzyme D425Q, in 50 mM HEPES (pH 7.0), at 30C
0.062
L-phenylalanine
-
mutant enzyme D425N, in 50 mM HEPES (pH 7.0), at 30C
0.1
L-phenylalanine
-
wild type enzyme, in 50 mM HEPES (pH 7.0), at 30C
0.2
L-phenylalanine
-
mutant enzyme D425K, in 50 mM HEPES (pH 7.0), at 30C
5
L-phenylalanine
-
mutant enzyme D425H, in 50 mM HEPES (pH 7.0), at 30C
0.051
L-Tyr
-
pH 7.1, 25C, wild-type enzyme
0.311
L-Tyr
-
pH 7.1, 25C, mutant enzyme H336Q
0.33
L-Tyr
-
pH 7.1, 25C, mutant enzyme H336E
0.00105
L-tyrosine
-
mutant enzyme D425T, in 50 mM HEPES (pH 7.0), at 30C
0.005
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S31A, cosubstrate 0.3 mM tetrahydropterin
0.006
L-tyrosine
-
mutant enzyme D425L, in 50 mM HEPES (pH 7.0), at 30C
0.0069
L-tyrosine
-
mutant enzyme D425M, in 50 mM HEPES (pH 7.0), at 30C
0.008
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S31E, cosubstrate 0.3 mM tetrahydropterin
0.0081
L-tyrosine
-
mutant enzyme R37E/R38E, pH and temperature not specified in the publication
0.0089
L-tyrosine
-
mutant enzyme D425S, in 50 mM HEPES (pH 7.0), at 30C
0.009
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S19A, cosubstrate 0.3 mM tetrahydropterin; pH 7.0, 30C, mutant enzyme S19E, cosubstrate 0.3 mM tetrahydropterin; pH 7.0, 30C, mutant enzyme S19E/S40E, cosubstrate 0.3 mM tetrahydropterin; pH 7.0, 30C, mutant enzyme S40E, cosubstrate 0.3 mM tetrahydropterin; pH 7.0, 30C, wild-type enzyme, cosubstrate 0.3 mM tetrahydropterin
0.01
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S40A, cosubstrate 0.3 mM tetrahydropterin
0.0106
L-tyrosine
-
mutant enzyme D425G, in 50 mM HEPES (pH 7.0), at 30C
0.011
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S8A, cosubstrate 0.3 mM tetrahydropterin; pH 7.0, 30C, mutant enzyme S8E, cosubstrate 0.3 mM tetrahydropterin
0.014
L-tyrosine
-
mutant enzyme K366L, pH and temperature not specified in the publication
0.015
L-tyrosine
-
mutant enzyme D425C, in 50 mM HEPES (pH 7.0), at 30C
0.015
L-tyrosine
-
mutant enzyme E362R/E365R, pH and temperature not specified in the publication
0.016
L-tyrosine
-
mutant enzyme D361N, pH and temperature not specified in the publication; mutant enzyme E362G, pH and temperature not specified in the publication; wild type enzyme, pH and temperature not specified in the publication
0.017
L-tyrosine
-
0-0.4 mM L-tyrosine, 1 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, 200 mM Na-HEPES pH 7.0, 100 mM 2-mercaptoethanol, 0.2 mg/ml catalase, 37C
0.0172
L-tyrosine
-
mutant enzyme D425F, in 50 mM HEPES (pH 7.0), at 30C
0.0187
L-tyrosine
-
mutant enzyme D425H, in 50 mM HEPES (pH 7.0), at 30C
0.019
L-tyrosine
-
mutant enzyme E365G, pH and temperature not specified in the publication
0.02
L-tyrosine
-
mutant enzyme A297L, pH and temperature not specified in the publication
0.024
L-tyrosine
-
W166F/W233F/W372F/F14W mutant protein, pH 7, 25C
0.025
L-tyrosine
-
mutant enzyme S368A, pH and temperature not specified in the publication
0.026
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S19E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.0263
L-tyrosine
-
recombinant wild type enzyme, at pH 7.5 and 37C
0.029
L-tyrosine
-
native wild type enzyme, at pH 7.5 and 37C
0.03
L-tyrosine
-
mutant enzyme Y423A, in 50 mM HEPES (pH 7.0), at 30C
0.0308
L-tyrosine
-
mutant enzyme D425Y, in 50 mM HEPES (pH 7.0), at 30C
0.035
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S19A, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.039
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T283M
0.04
L-tyrosine
-
30C
0.04
L-tyrosine
-
wild type protein, pH 7, 25C
0.04
L-tyrosine
-
mutant enzyme D425V, in 50 mM HEPES (pH 7.0), at 30C; wild type enzyme, in 50 mM HEPES (pH 7.0), at 30C
0.041
L-tyrosine
-
pH 7.0, 30C, wild-type enzyme, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.041
L-tyrosine
-
mutant enzyme D425I, in 50 mM HEPES (pH 7.0), at 30C
0.042
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S8A, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.042
L-tyrosine
-
pH 7.0, 30C, mutant enzyme R306H
0.0428
L-tyrosine
-
mutant enzyme E434A, at pH 7.5 and 37C
0.043
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T463M
0.043
L-tyrosine
-
W166F/W233F/W372F/F74W mutant protein, pH 7, 25C
0.044
L-tyrosine
-
mutant enzyme Q424A, in 50 mM HEPES (pH 7.0), at 30C
0.046
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S40A, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.046
L-tyrosine
-
pH 7.0, 30C, wild-type enzyme
0.047
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S40E, cosubstrate 0.4 mM 6-methyltetrahydropterin; pH 7.0, 30C, mutant enzyme S8E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.051
L-tyrosine
-
mutant enzyme T427A, in 50 mM HEPES (pH 7.0), at 30C
0.053
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S31E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.055
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S31A, cosubstrate 0.4 mM 6-0.053 methyltetrahydropterin
0.056
L-tyrosine
-
mutant enzyme D425A, in 50 mM HEPES (pH 7.0), at 30C
0.058
L-tyrosine
-
W166F/W233F/W372F/F34W mutant protein, pH 7, 25C
0.059
L-tyrosine
-
pH 7.0, 30C, mutant enzyme S19E/S40E, cosubstrate 0.4 mM 6-methyltetrahydropterin
0.066
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T245P
0.066
L-tyrosine
-
mutant enzyme Q426A, in 50 mM HEPES (pH 7.0), at 30C
0.08
L-tyrosine
-
0.38 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, 0.1 mg/ml catalase, 50 mM HEPES pH 7.0, 0.01 mM ferrous ammonium sulfate, 1 mM dithiothreitol, 25C
0.088
L-tyrosine
-
mutant enzyme D425R, in 50 mM HEPES (pH 7.0), at 30C
0.097
L-tyrosine
-
mutant enzyme D425E, in 50 mM HEPES (pH 7.0), at 30C
0.162
L-tyrosine
-
mutant enzyme D425Q, in 50 mM HEPES (pH 7.0), at 30C
0.172
L-tyrosine
-
mutant enzyme D425N, in 50 mM HEPES (pH 7.0), at 30C
0.8086
L-tyrosine
-
pH 6.0, 37C
0.006
O2
-
below, recombinant enzyme
0.00125
phenylalanine
-
recombinant mutant D425V
0.0077
phenylalanine
-
recombinant mutant H323Y
0.0088
phenylalanine
-
recombinant mutant Q310H
0.01
phenylalanine
-
recombinant mutant Y371F
0.085
phenylalanine
-
-
0.1
phenylalanine
-
recombinant wild-type
0.11
phenylalanine
-
recombinant wild-type
0.3
phenylalanine
-
bovine adrenal
0.0041
tetrahydrobiopterin
-
pH 7.0, 37C
0.0056
tetrahydrobiopterin
-
wild type, phosphorylated protein, pH 7.2, 30C
0.0068
tetrahydrobiopterin
-
wild type protein, dopamine bound but removed from low-affinity site, pH 7.2, 30C
0.0072
tetrahydrobiopterin
-
E332D phosphorylated mutant protein, pH 7.2, 30C
0.0083
tetrahydrobiopterin
-
E332D mutant protein, pH 7.2, 30C
0.009
tetrahydrobiopterin
-
pH 7.0, 30C, mutant enzyme T463M
0.0099
tetrahydrobiopterin
-
L294Y phosphorylated mutant protein, pH 7.2, 30C
0.01
tetrahydrobiopterin
-
pH 7.0, 30C, mutant enzyme R306H; pH 7.0, 30C, mutant enzyme T283M
0.012
tetrahydrobiopterin
-
F300Y phosphorylated mutant protein, pH 7.2, 30C
0.013
tetrahydrobiopterin
-
pH 7.0, 30C, wild-type enzyme
0.014
tetrahydrobiopterin
-
pH 7.0, 30C, mutant enzyme T245P
0.014
tetrahydrobiopterin
-
L294A mutant protein, pH 7.2, 30C; wild type protein, pH 7.2, 30C
0.015
tetrahydrobiopterin
-
L294Y mutant protein, pH 7.2, 30C
0.017
tetrahydrobiopterin
-
A297L phosphorylated mutant protein, pH 7.2, 30C; Y371F mutant protein, pH 7.2, 30C
0.02
tetrahydrobiopterin
-
A297L mutant protein, pH 7.2, 30C
0.026
tetrahydrobiopterin
-
F300Y mutant protein, pH 7.2, 30C
0.027
tetrahydrobiopterin
-
A297L mutant protein, dopamine bound to the high-affinity site, pH 7.2, 30C; Y371F mutant protein, dopamine bound to the high-affinity site, pH 7.2, 30C
0.029
tetrahydrobiopterin
-
L294A phosphorylated mutant protein, pH 7.2, 30C; Y371F phosphorylated mutant protein, pH 7.2, 30C
0.034
tetrahydrobiopterin
-
E332D mutant protein, dopamine bound to the high-affinity site, pH 7.2, 30C
0.04
tetrahydrobiopterin
-
wild type protein, pH 7, 25C
0.0426
tetrahydrobiopterin
-
pH 6.9, 37C
0.0471
tetrahydrobiopterin
-
native wild type enzyme, at pH 7.5 and 37C
0.0519
tetrahydrobiopterin
-
recombinant wild type enzyme, at pH 7.5 and 37C
0.054
tetrahydrobiopterin
-
F300A mutant protein, pH 7.2, 30C
0.055
tetrahydrobiopterin
-
W166F/W233F/W372F/F14W mutant protein, pH 7, 25C
0.065
tetrahydrobiopterin
-
W166F/W233F/W372F/F74W mutant protein, pH 7, 25C
0.07
tetrahydrobiopterin
-
F300A phosphorylated mutant protein, pH 7.2, 30C
0.077
tetrahydrobiopterin
-
W166F/W233F/W372F/F34W mutant protein, pH 7, 25C
0.134
tetrahydrobiopterin
-
wild type protein, dopamine bound to the high-affinity site, pH 7.2, 30C
0.341
tetrahydrobiopterin
-
mutant enzyme E434A, at pH 7.5 and 37C
0.356
tetrahydrobiopterin
-
wild type protein, in the presence of dopamine, pH 7.2, 30C
0.507
tetrahydrobiopterin
-
wild type, phosphorylated protein, in the presence of dopamine, pH 7.2, 30C
0.01
Tetrahydropterin
-
recombinant phosphorylated hTH1, L-dopa-oxidase activity
0.021
Tetrahydropterin
-
recombinant enzyme, value is pH-dependent
0.027
Tetrahydropterin
-
recombinant wild-type, pH 7.1
0.045
Tetrahydropterin
-
-
0.053
Tetrahydropterin
-
recombinant mutant Y371F, pH 7.1
0.08
Tetrahydropterin
-
low Km form
0.63
Tetrahydropterin
-
high Km form
1.1
tyramine
-
pH 7.0, 37C
0.0061
tyrosine
-
-
0.0094
tyrosine
-
recombinant enzyme, pH-independent
0.0095
tyrosine
-
-
0.011
tyrosine
-
-
0.016
tyrosine
-
recombinant wild-type
0.032
tyrosine
-
recombinant wild-type, pH 6.0
0.045
tyrosine
-
recombinant mutant D425V
0.05
tyrosine
-
bovine adrenal gland
0.051
tyrosine
-
recombinant wild-type, pH 7.1
0.054
tyrosine
-
recombinant mutant Q310H
0.055
tyrosine
-
recombinant isoform hTH2, with 6-methyltetrahydropterin
0.065
tyrosine
-
recombinant mutant Y371F, pH 7.1
0.066
tyrosine
-
recombinant isoform hTH4, with 6-methyltetrahydropterin
0.071
tyrosine
-
recombinant mutant Y371F, pH 6.0
0.074
tyrosine
-
recombinant isoform hTH3, with 6-methyltetrahydropterin
0.075
tyrosine
-
with 6-methyltetrahydropterin
0.092
tyrosine
-
recombinant mutant H323Y
0.166
tyrosine
-
recombinant isoform hTH1, with 6-methyltetrahydropterin
0.5
tyrosine
-
-
2.39
L-tyrosine
-
mutant enzyme D425K, in 50 mM HEPES (pH 7.0), at 30C
additional information
additional information
-
-
-
additional information
additional information
-
effect of RNA on Km
-
additional information
additional information
-
effect of RNA on Km; rat brain: 2 kinetically distinguishable forms: low Km form, high Km form
-
additional information
additional information
-
Km dependence on substrate concentrations
-
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; rat brain: 2 kinetically distinguishable forms: low Km form, high Km form
-
additional information
additional information
-
Km is dependent on substrate and cofactor concentration when (6R)-L-erythro-tetrahydrobiopterin is used due to inhibitory effects
-
additional information
additional information
-
Km dependence on substrate concentrations
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
Km dependent on cosubstrate type and concentration, overview for 4 isoforms
-
additional information
additional information
-
Km-values for tyrosine of mutant phenylalanine hydroxylase with tyrosine hydroxylation activity
-
additional information
additional information
-
Km-values of diverse tetrahydropterin analogues, substituted at C6, C7 or C3
-
additional information
additional information
-
kinetics analysis, overview
-
additional information
additional information
-
both the cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin and the feedback inhibitor dopamine increase the kinetic stability of human isozyme 1 in vitro
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.8
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T283M
1.7
L-tyrosine
-
W166F/W233F/W372F/F74W mutant protein, pH 7, 25C
1.8
L-tyrosine
-
W166F/W233F/W372F/F14W mutant protein, pH 7, 25C
2
L-tyrosine
-
W166F/W233F/W372F/F34W mutant protein, pH 7, 25C
2.5
L-tyrosine
-
wild type protein, pH 7, 25C
3.03
L-tyrosine
-
0.1 mM L-tyrosine, 0.1 mg/ml catalase, 50 mM HEPES pH 7.0, 0.01 mM ferrous ammonium sulfate, 1 mM dithiothreitol, 25C
3.33
L-tyrosine
-
pH 7.0, 30C, wild-type enzyme
3.68
L-tyrosine
-
pH 7.0, 30C, mutant enzyme R306H
3.87
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T463M
5.35
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T245P
0.017
tetrahydrobiopterin
-
wild type protein, in the presence of 0.01 mM dopamine, pH 7.2, 30C
0.047
tetrahydrobiopterin
-
E332D phosphorylated mutant protein, pH 7.2, 30C
0.06
tetrahydrobiopterin
-
E332D mutant protein, pH 7.2, 30C
0.068
tetrahydrobiopterin
-
L294Y phosphorylated mutant protein, pH 7.2, 30C
0.088
tetrahydrobiopterin
-
F300A mutant protein, pH 7.2, 30C
0.11
tetrahydrobiopterin
-
F300A phosphorylated mutant protein, pH 7.2, 30C
0.12
tetrahydrobiopterin
-
L294Y mutant protein, pH 7.2, 30C
0.14
tetrahydrobiopterin
-
L294A phosphorylated mutant protein, pH 7.2, 30C
0.18
tetrahydrobiopterin
-
L294A mutant protein, pH 7.2, 30C
0.2
tetrahydrobiopterin
-
Y371F mutant protein, pH 7.2, 30C
0.22
tetrahydrobiopterin
-
A297L phosphorylated mutant protein, pH 7.2, 30C
0.27
tetrahydrobiopterin
-
A297L mutant protein, pH 7.2, 30C; F300Y phosphorylated mutant protein, pH 7.2, 30C
0.3
tetrahydrobiopterin
-
F300Y mutant protein, pH 7.2, 30C; Y371F phosphorylated mutant protein, pH 7.2, 30C
0.47
tetrahydrobiopterin
-
wild type, phosphorylated protein, pH 7.2, 30C
0.58
tetrahydrobiopterin
-
wild type protein, pH 7.2, 30C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.7
tetrahydrobiopterin
-
F300A mutant protein, pH 7.2, 30C; F300A phosphorylated mutant protein, pH 7.2, 30C
252
5
tetrahydrobiopterin
-
L294A phosphorylated mutant protein, pH 7.2, 30C
252
6.5
tetrahydrobiopterin
-
E332D phosphorylated mutant protein, pH 7.2, 30C
252
7
tetrahydrobiopterin
-
L294Y phosphorylated mutant protein, pH 7.2, 30C
252
7.3
tetrahydrobiopterin
-
E332D mutant protein, pH 7.2, 30C
252
7.7
tetrahydrobiopterin
-
L294Y mutant protein, pH 7.2, 30C
252
10.7
tetrahydrobiopterin
-
Y371F phosphorylated mutant protein, pH 7.2, 30C
252
11.2
tetrahydrobiopterin
-
F300Y mutant protein, pH 7.2, 30C
252
11.7
tetrahydrobiopterin
-
Y371F mutant protein, pH 7.2, 30C
252
12.5
tetrahydrobiopterin
-
A297L phosphorylated mutant protein, pH 7.2, 30C
252
13
tetrahydrobiopterin
-
L294A mutant protein, pH 7.2, 30C
252
13.7
tetrahydrobiopterin
-
A297L mutant protein, pH 7.2, 30C
252
21.8
tetrahydrobiopterin
-
F300Y phosphorylated mutant protein, pH 7.2, 30C
252
45.7
tetrahydrobiopterin
-
wild type protein, pH 7.2, 30C
252
89.3
tetrahydrobiopterin
-
wild type, phosphorylated protein, pH 7.2, 30C
252
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.07
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
pH 7.0, 25C, versus (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
0.016
2,4-diamino-6-dihydroxypropyl-5,6,7,8-tetrahydropterin
-
-
0.18
2-hydroxyestradiol-17beta
-
enzyme from telencephalom, resting phase
0.22
2-hydroxyestradiol-17beta
-
enzyme from hypothalamus, resting phase
0.25
2-hydroxyestradiol-17beta
-
enzyme from telencephalon, resting phase
0.28
2-hydroxyestradiol-17beta
-
enzyme from hypothalamus, preparatory phase
0.011
3-iodo-L-tyrosine
-
versus tetrahydrobiopterin
0.024
3-iodo-L-tyrosine
-
versus tyrosine, in presence of tetrahydrobiopterin
2.83
5(N-phenylthiocarbamoyl)-5,6,7,8-tetrahydropterin
-
-
0.063
5-methyl-5,6,7,8-tetrahydropterin
-
-
0.001
6-[2-(4-benzoylphenyl)propionyloxymethyl]-5,6,7,8-tetrahydropterin
-
-
0.138
7-amino-3,3a,4,5-tetrahydro-8H-2-oxa-5,6,8,9b-tetraaza-cyclopenta[a]naphthalene-1,9-dione
-
-
0.617
8-methyl-6,7-dimethyl-5,6,7,8-tetrahydropterin
-
-
0.3
adrenaline
-
enzyme from hypothalamus, preparatory phase
0.32
adrenaline
-
enzyme from telencephalon, resting phase
0.35
adrenaline
-
enzyme from telencephalom, resting phase
0.4
adrenaline
-
enzyme from hypothalamus, resting phase
0.52
dopamine
-
enzyme from hypothalamus, preparatory phase; enzyme from telencephalon, resting phase
0.6
dopamine
-
enzyme from telencephalom, resting phase
0.69
dopamine
-
enzyme from hypothalamus, resting phase
0.07
L-erythro-7,8-dihydrobiopterin
-
-
0.103
L-phenylalanine
-
0-0.4 mM L-tyrosine, 0-0.2 mM L-phenylalanine, 1 mM 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine, 200 mM Na-HEPES pH 7.0, 100 mM 2-mercaptoethanol, 0.2 mg/ml catalase, 37C
0.037
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T283M
0.044
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T463M
0.046
L-tyrosine
-
pH 7.0, 30C, wild-type enzyme
0.048
L-tyrosine
-
pH 7.0, 30C, mutant enzyme R306H
0.25
noradrenaline
-
enzyme from hypothalamus, preparatory phase
0.28
noradrenaline
-
enzyme from telencephalon, resting phase
0.3
noradrenaline
-
enzyme from hypothalamus, resting phase
0.32
noradrenaline
-
enzyme from telencephalom, resting phase
0.073
L-tyrosine
-
pH 7.0, 30C, mutant enzyme T245P
additional information
additional information
-
value dependent on electron donor, overview
-
additional information
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0022
3,4-dihydroxy-L-phenylalanine
-
at pH 7.0 and 25C
0.0326
3,4-dihydroxy-L-phenylalanine
-
at pH 7.0 and 25C
0.05
3-iodo-L-tyrosine
-
pH and temperature not specified in the publication
0.0002
dopamine
-
-
0.000256
dopamine
-
wild type, phosphorylated protein, pH 7.2, 30C
0.0004
dopamine
-
wild type protein, pH 7.2, 30C
0.000595
dopamine
-
wild type enzyme, pH and temperature not specified in the publication
0.000645
dopamine
-
mutant enzyme K170E/L480A, pH and temperature not specified in the publication
0.00093
dopamine
-
F300Y mutant protein, pH 7.2, 30C
0.00098
dopamine
-
Y371F mutant protein, pH 7.2, 30C
0.00107
dopamine
-
L294A mutant protein, pH 7.2, 30C
0.00143
dopamine
-
E332D mutant protein, pH 7.2, 30C
0.00248
dopamine
-
E332D phosphorylated mutant protein, pH 7.2, 30C
0.0136
dopamine
-
E332D phosphorylated mutant protein, pH 7.2, 30C
0.0003
N-methyl-norsalsolinol
-
-
0.004
N-methyl-salsolinol
-
-
0.01
norsalsolinol
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00003
-
crude extract
0.0002
-
about, MN9D cells
0.00045
-
about, MN9D cells induced by forskolin or 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate
0.00368
-
activity of tyrosine hydroxylase, control level without treatment of L-DOPA in PC-12 cells
0.0054
-
crude enzyme, at pH 6.8 and 37C
0.0163
-
purified enzyme, at pH 6.8 and 37C
0.03 - 0.1
-
recombinant enzyme, cell lysate
0.04
-
purified enzyme
0.0447
-
activity in melanosomes
0.0916
-
purified enzyme from brain
0.16
-
purified recombinant isoform hTH3
0.18
-
purified enzyme from adrenal medulla
0.2
-
purified recombinant isoform hTH4
0.2
-
purified enzyme
0.21
-
purified enzyme
0.29
-
purified recombinant isoform hTH2
0.33
-
purified recombinant isoform hTH1, tyrosine concentration is 0.2 mM
0.36
-
purified enzyme
0.41
-
purified enzyme
0.425
-
purified enzyme
0.78
-
purified enzyme
0.79
-
purified recombinant isoform hTH1, tyrosine concentration is 0.05 mM
0.82
-
pH 6.9, 37C
1
-
about, purified recombinant enzyme
1.6
-
purified enzyme
1.7
-
purified, recombinant enzyme
1.88
-
purified enzyme
2.5
-
purified enzyme, tyrosine concentration is 0.2 mM
3.46
-
purified enzyme, immobilized
20.7
-
purified enzyme, tyrosine concentration is 0.05 mM
101
-
L-tyramine, crude extract of mature leaves, pH 6.0, 37C
113
-
L-tyrosine, crude extract of mature leaves, pH 6.0, 37C
330
-
purified enzyme
1604
-
purified enzyme
68800
-
with 1 mM L-tyrosine, at pH 7.0 and 25C
555000
-
with 0.05 mM L-tyrosine, at pH 7.0 and 25C
additional information
-
activity of immobilized enzyme under different conditions in bioreactors
additional information
-
dopa-oxidase activity of the 4 isoforms
additional information
-
-
additional information
-
determination of catecholamine secretion
additional information
-
-
additional information
-
tyrosine hydroxylase expression and activity in wild-type MN9D cells, in alpha-synuclein-deficient MN9D cells, and in MN9D cells transfected with alpha-synuclein, overview
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; 232% activity compared to control level, treatment with 0.1 mM L-DOPA in PC-12 cells at 6 h time point; 272% activity compared to control level, treatment with 0.02 mM L-DOPA in PC-12 cells at 6 h time point; 55.2% activity compared to control level, treatment with 0.2 mM L-DOPA in PC-12 cells at 48 h time point; 62.6% activity compared to control level, treatment with 0.2 mM L-DOPA in PC-12 cells at 1 h time point; 68.2% activity compared to control level, treatment with 0.1 mM L-DOPA in PC-12 cells at 1 h time point; 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; 82.3% activity compared to control level, treatment with 0.1 mM L-DOPA in PC-12 cells at 48 h time point; activity returns to the control level between 24-48 h after treatment with 0.02 mM L-DOPA.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.4 - 5.5
-
crude extract
5.5 - 6
-
striatal homogenate
5.9
-
nonphosphorylated enzyme
6 - 7
-
4 isoforms
6 - 7.5
-
purified enzyme
6
-
broad optimum pH 4.0-7.5
6.2
-
-
7
-
broad optimum, recombinant enzyme
7
-
recombinant enzyme isoforms, L-dopa-oxidase activity
7
-
recombinant hTH1, assay at
7
-
assay at
7
-
assay at
7
-
assay at
7.1
-
assay at
7.2
-
assay at
7.4
-
assay at
7.4
-
assay at
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 - 8.5
-
4 isoforms
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
5.9 - 7.4
-
activity declines precipitously below pH 5.9 and above pH 7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 30
-
assay at
25
-
assay at
25
-
recombinant hTH1, assay at
25
-
assay at
25
-
assay at, recombinant enzyme
30
-
assay at
30
-
assay at, crude brain enzyme extract
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.35
A5YVV2
predicted
5.43
-
sequence calculation
5.81
-
predicted
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
tyrosine hydroxylase in hypertensive rats shows 35% lower expression and a reduced Vmax due to a decreased phosphorylation at Ser40
Manually annotated by BRENDA team
-
2fold activity under cold stress. Injection of the angiotensin converting enzyme inhibitor enalapril malate prevented the increase of tyrosine hydroxylase under cold stress
Manually annotated by BRENDA team
A5YVV2
7 daysold
Manually annotated by BRENDA team
Tribolium castaneum GA-1
-
7 daysold
-
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
immunohistochemic analysis of tyrosine hydroxylase
Manually annotated by BRENDA team
-
nucleus accumbens and dorsal striatum
Manually annotated by BRENDA team
-
of wild-type and striatal 6-hydroxydopamine lesioned rats
Manually annotated by BRENDA team
-
substantia nigra and ventral tegmental areas
Manually annotated by BRENDA team
-
isoenzyme DHT1 is selectively expressed in central nervous system. DTH1 cannot perform the function of the DTH II in the hypoderm
Manually annotated by BRENDA team
-
immunohistochemic analysis of the enzyme distribution in mesencephalon, diencephalon, and telencephalon, detailed overview
Manually annotated by BRENDA team
-
ataxic and control, high enzyme expression level in ataxic mice, dramatic difference in cerebellar tyrosine hydroxylase immunoreactivity between mutant pogo, wild-type, and mutant p35-/- and p39-/- mice, overview
Manually annotated by BRENDA team
-
developing, intereurons, the majority of cortical tyrosine hydroxylase cells at all ages contains phosphorylated tyrosine hydroxylase
Manually annotated by BRENDA team
-
dorsal striatum
Manually annotated by BRENDA team
-
myenteric ganglion
Manually annotated by BRENDA team
-
enzyme expression at the stage when the pharate larval cuticle begins to tan
Manually annotated by BRENDA team
Tribolium castaneum GA-1
-
-
-
Manually annotated by BRENDA team
-
cells in the basal forebrain
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
2fold activity under cold stress. Injection of the angiotensin converting enzyme inhibitor enalapril malate prevented the increase of tyrosine hydroxylase under cold stress
Manually annotated by BRENDA team
-
isoenzyme DHT2 is selectively expressed in central nervous system. DTH1 cannot perform the function of the DTH II in the hypoderm
Manually annotated by BRENDA team
-
anterior and posterior
Manually annotated by BRENDA team
-
2fold activity under cold stress. Injection of the angiotensin converting enzyme inhibitor enalapril malate prevented the increase of tyrosine hydroxylase under cold stress
Manually annotated by BRENDA team
-
the enzyme content is reduced in the hypothalamic paraventricular nucleus, neurons and neuropil, of the seizure-sensitive gerbils
Manually annotated by BRENDA team
-
in some cells of the hypothalamus, tyrosine hydroxylase is colocalized with vasoactive intestinal peptide
Manually annotated by BRENDA team
-
undifferentiated, hydroxylase isoenzyme I mRNA, no detection of isoenzyme 2, 3 and 4
Manually annotated by BRENDA team
-
enzyme expression in the integument of molting larvae
Manually annotated by BRENDA team
-
anterior and posterior
Manually annotated by BRENDA team
-
increased enzyme contents in violent suicidal depressive patients, analysis of postmortem brains of control individuals, non-suicidal depressive patients, and non-violent and violent suicidal depressive patients
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
epidermal, hydroxylase isoenzyme I mRNA, no detection of isoenzyme 2, 3 and 4
Manually annotated by BRENDA team
-
ventral mesencephalon
Manually annotated by BRENDA team
-
treatment with the parasite-derived neurotrophic factor of Trypanosoma cruzi increased the number of tyrosine hydroxylase expressing neurons
Manually annotated by BRENDA team
-
midbrain dopaminergic neurons, expression analysis in situ
Manually annotated by BRENDA team
-
a dopaminergic cell line, generated by fusion of rostral mesencephalic neurons from embryonic C57BL/6J mice with N18TG2 neuroblastoma cells
Manually annotated by BRENDA team
-
a hybrid cell line derived from the fusion of mouse neuroblastoma N18TG2 cells with embryonic mouse mesencephalic neurons, tyrosine hydroxylase polysome profile analysis, overview
Manually annotated by BRENDA team
-
neuropil, tyrosine hydroxylase-immunoreactive nerve terminals are distributed throughout the ganglia and contained exclusively pleomorphic clear synaptic vesicles
Manually annotated by BRENDA team
-
neuroblastoma cells
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
neuroblastoma cells
-
Manually annotated by BRENDA team
-
sympathetic, innervated
Manually annotated by BRENDA team
-
37 different tumor samples, analysis of enzyme expression
Manually annotated by BRENDA team
-
amount of immunoreactive neurons in seizure-sensitive and seizure-resistant gerbils, overview
Manually annotated by BRENDA team
-
dopaminergic neurons
Manually annotated by BRENDA team
-
fibers and puncta
Manually annotated by BRENDA team
-
hypothalamic domainergic neurons
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
midbrain dopaminergic neurons, expression analysis in situ
Manually annotated by BRENDA team
-
myenteric, about 16% of the total number of axosomatic terminals show tyrosine hydroxylase immunoreactivity
Manually annotated by BRENDA team
-
non-monoaminergic neurons, immunohistochemic analysis of enzyme distribution, overview
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
mid brain dopamine neuron
Manually annotated by BRENDA team
-
primary cell culture
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
a pheochromocytoma cell line
Manually annotated by BRENDA team
-
derived from a pheochromocytoma of the rat adrenal medulla
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
in some cells of the pituitary gland, tyrosine hydroxylase is colocalized with vasoactive intestinal peptide, in the intermediate and neuronal lobes of the pituitary tyrosine hydroxylase is expressed in glial fibrillary acidic protein-contained cells
Manually annotated by BRENDA team
A5YVV2
5 days old
Manually annotated by BRENDA team
Tribolium castaneum GA-1
-
5 days old
-
Manually annotated by BRENDA team
-
a dopaminergic-like, neuroblastoma cell line
Manually annotated by BRENDA team
-
a dopaminergic cell line
Manually annotated by BRENDA team
-
the paraventricular nucleus of the hypothalamus and the central amygdala
Manually annotated by BRENDA team
-
contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
preoptic, contains tyrosine hydroxylase-immunoreactive neurons
Manually annotated by BRENDA team
-
the superior cervical ganglion of the sympathetic nervous system is filled with many neuronal somata and fibers with strong immunoreactivity for tyrosine hydroxylase, TH-positive fibers are not evenly distributed within the nerve bundles of the ganglia, but tend to be located at their circumference
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
a dopaminergic cell line, generated by fusion of rostral mesencephalic neurons from embryonic C57BL/6J mice with N18TG2 neuroblastoma cells
-
Manually annotated by BRENDA team
additional information
-
mice treated with raclopride show an increased phosphorylation of tyrosine hydroxylase and an increased production of dihydroxyphenylalanine. Additional treatment with L-tyrosine does not enhance this effect, mice treated with raclopride show an increased phosphorylation of tyrosine hydroxylase and an increased production of dihydroxyphenylalanine. Additional treatment with L-tyrosine enhances this effect
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
additional information
-
comparison of enzyme expressing cells of the diurnal rodent Arvicanthis niloticus with the enzyme of the nocturnal rodent Rattus norvegicus, vasoactive intestinal polypeptide colocalizes with the enzyme, enzyme distribution, overview
Manually annotated by BRENDA team
additional information
-
comparison of the distributions of tyrosine hydroxylase and aromatic-Lamino acid decarboxylase, AADC, which catalyzes the back reaction of the tyrosine hydroxylase reaction, in the brain regions, overview
Manually annotated by BRENDA team
additional information
-
cortical tyrosine hydroxylase neurons colocalizes with calretinin but not with parvalbumin or somatostatin
Manually annotated by BRENDA team
additional information
-
immunohistochemic analysis of enzyme content in neurons of wild-type and striatal 6-hydroxydopamine lesioned rats, overview
Manually annotated by BRENDA team
additional information
-
immunohistochemic enzyme analysis in brain slices, overview
Manually annotated by BRENDA team
additional information
-
no enzyme in cerebellum, rhombencephalon, spinal cord, and pituitary gland
Manually annotated by BRENDA team
additional information
-
tissue enzyme expression profile, overview
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
-
mutant enzymes T283M and R306H expressed in Escherichia coli are mainly found in inclusion bodies but a small amount of soluble enzyme is produced
Manually annotated by BRENDA team
-
particle-bound
Manually annotated by BRENDA team
-
molecules phosphorylated at Ser19 are found mainly in the nucleus
Manually annotated by BRENDA team
-
mutant enzyme T245P and T463 M expressed in Escherichia coli are predominantly soluble. Mutant enzymes T283M and R306H expressed in Escherichia coli are mainly found in inclusion bodies but a small amount of soluble enzyme is produced
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
24000
-
sucrose density gradient centrifugation
438696
24000
-
4 isoforms, gel filtration
438705
62000
-
SDS-PAGE
700464
98900
-
recombinant enzyme, SDS-PAGE
676182
210000 - 211000
-
gel filtration
438683
210000 - 211000
-
adrenal, gel filtration
438684
225000
-
pheochromocytoma tumors, asymmetric protein, native PAGE, gel filtration and sucrose density gradient centrifugation
438690
239000
-
brain, gel filtration
438683
250000
-
gel filtration
438692
250000
-
about, recombinant enzyme, gel filtration
687087
260000
-
from adrenal medulla
438654
260000
-
gel filtration
438688, 438698
280000
-
-
438654
280000
-
gel filtration
438687, 438694
280000
-
form I; gel filtration
438695
300000
-
gel filtration
727798
310000
-
from caudate nucleus, gel filtration
438695
390000
-
from adrenal medulla, form II, gel filtration
438695
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; peripheral noradrenergic neurons in superior cervical ganglion: MW 130000 Da
438654
additional information
-
-
438698
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 62000, SDS-PAGE
?
-
x * 56000, SDS-PAGE
?
-
x * 66200, SDS-PAGE
?
-
x * 58000, recombinant enzyme, SDS-PAGE
?
-
x * 58000-62000, tyrosine hydroxylase isozymes, SDS-PAGE, identification by mass spectrometry
?
-
x * 54000, predicted, 55 kDa from SDS-PAGE of His-tagged version
?
-
x * 55000, SDS-PAGE, Western blot analysis
?
A5YVV2
x * 60000, Western blot analysis, 60.4 kDa predicted
?
Tribolium castaneum GA-1
-
x * 60000, Western blot analysis, 60.4 kDa predicted
-
homotetramer
-
-
homotetramer
-
4 * 70000, SDS-PAGE
tetramer
-
4 * 62000
tetramer
-
4 * 60000, SDS-PAGE
tetramer
-
4 * 60000, SDS-PAGE
tetramer
-
4 * 59000, SDS-PAGE
tetramer
-
4 * 63300, SDS-PAGE
tetramer
-
2 * 61100 + 2 * 62400, SDS-PAGE
tetramer
-
4 * 55000, recombinant enzyme, SDS-PAGE
tetramer
-
4 * 60000, 4 isoforms, SDS-PAGE
tetramer
-
4 * 56000, about, pheochromocytoma tumor, SDS-PAGE and amino acid sequence analysis
tetramer
-
4 * 63100, about, recombinant enzyme, sequence calculation and gel filtration
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
no glycoprotein
-
-
phosphoprotein
-
the enzyme is phospbhorylated at Ser19, Ser31, and Ser40 and thereby activated, the activation is completely blocked by EGTA
phosphoprotein
-
the enzyme is phosphorylated at Ser35 by cAMP-dependent protein kinase
phosphoprotein
Caenorhabditis elegans N2 Bristol
-
the enzyme is phosphorylated at Ser35 by cAMP-dependent protein kinase
-
phosphoprotein
-
the enzyme is activated by cAMP-dependent protein kinase in vitro
phosphoprotein
-
-
phosphoprotein
-
activation through phosphorylation of tyrosine hydroxylase by cyclic AMP-dependent protein kinase A, inhibited in the presence of H89
phosphoprotein
-
enzyme activation by reversible phosphorylation, phosphorylation by protein kinase A at Ser40, the most prominent of these regulatory sites, increases the dissociation rate of bound catecholamine feedback inhibitors
phosphoprotein
-
phosphorylation at Ser40 activates the enzyme, the phosphorylationis inhibited by alpha-synuclein, up to 183% induced by amphetamines, the phosphorylation inhibition is inhibited by melatonin, mechanisms, overview
phosphoprotein
-
phosphorylation of Ser40 directly increases tyrosine hydroxylase activity by inducing a 500fold increase in the rate of dissociation of the catecholamines from the high affinity site of tyrosine hydroxylase, phosphorylation of Ser31 induces a small (1.2-2fold) increase in tyrosine hydroxylase activity in vitro primarily by decreasing the KM for the cosubstrate tetrahydrobiopterin, prior phosphorylation of Ser19 or Ser31 is able to increase the rate of phosphorylation of Ser40 by approximately 3fold and 9fold, respectively. Isoform TH1 is phosphorylated at Ser31 in vitro by extracellular signal-regulated protein kinase, while isoform TH2 cannot be phosphorylated at the equivalent Ser31 residue (Ser35) by extracellular signalregulated protein kinase.
phosphoprotein
-
Ser31 and Ser40 are readily phosphorylated to activate tyrosine hydroxylase type 1 in vitro. Although phosphorylation of Ser19 does not directly activate tyrosine hydroxylase, chaperone 14-3-3 protein binds and activates tyrosine hydroxylase at Ser19 phosphorylated by Ca2+/calmodulin-dependent protein kinase II.
phosphoprotein
-
the enzyme is phosphorylated at Ser40 by cAMP-dependent protein kinase
phosphoprotein
-
the enzyme is phosphorylated by cAMP-dependent protein kinases at serine residues, e.g. Ser31
phosphoprotein
-
cyclin-dependent kinase 5 phosphorylates tyrosine hydroxylase, but does not induce the enzyme expression
phosphoprotein
-
phosphorylation at Ser40 activates the enzyme
phosphoprotein
-
reversible phosphorylation at Ser40 regulates the enzyme activity, the phosphorylated enzyme is active, dephosphorylation is performed by phosphatase PP2A, PKCdelta physically associates with the PP2A catalytic subunit and phosphorylates the phosphatase to increase its activity, it also physically associates with tyrosine hydroxylase, inhibition of PKCdelta reduces the dephosphorylation activity of PP2A and thereby increases TH-Ser40 phosphorylation, tyrosine hydroxylase activity, and dopamine synthesis, overview
phosphoprotein
-
short term regulation of tyrosine hydroxylase depends on the phosphorylation of seryl residues, Ser19, Ser31, and Ser40, in the TH regulatory domain, activating phosphorylation at Ser40 is inhibited by alpha-synuclein
phosphoprotein
Mus musculus C57BL/6J
-
phosphorylation at Ser40 activates the enzyme
-
no glycoprotein
-
-
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 activates the tyrosine hydroxylase
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
-
phosphorylation of Ser40 activates the enzyme
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
phosphoprotein
-
the enzyme is phosphorylated at Ser40 by protein kinase A
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
complex of 14-3-3gamma protein and phosphorylated tyrosine hydroxylase(1-43), sitting drop vapor diffusion method, using 30% (w/v) polyethylene glycol 2000 monomethyl ether as precipitant
-
crystal structure, analysis of tetrahydropterin analogues binding to isoform hTH1
-
3D-structure model, ligand binding of pterin analogues; 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 4C
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
preincubation at 37C for 2 h above, isoforms are stable; preincubation at 37C for 2 h below, enzyme isoforms are unstable, especially isoforms hTH1 and hTH3
438705
8
-
isoforms, optimal stability at
438705
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
5 h, without stabilizing agent, complete loss of activity
438698
20 - 45
-
60 min
716647
37
-
unstable in presence of phosphatidylinositol or NaCl at high concentration, but relatively stable in presence of heparin
438696
37
-
5 h, stable, catecholamine, N-methyl-norsalsolinol, or norsalsolinol binding increases the thermal stability of tyrosine hydroxylase
686696
40 - 65
-
minimal aggregation occurs for wild type enzyme after heating at 40C-45 for 60 min. A steep decrease in activity is observed between 40 and 65C, and a complete loss of activity occurs at temperatures above 70C
728715
41
-
Tm-value of mutant enzyme T463M is 44.3C
660477
42
-
or below, all mutant enzymes are stable for at least 1 h
657679
44
-
Tm-value of mutant enzyme T245P is 44.3C
660477
45
-
in presence of 2% glycerol, enzymes lose activity in time-dependent manner
657679
46
-
Tm-value of mutant enzyme R306H is 45.8C
660477
48
-
Tm-value of wild-type enzyme is 48.2C
660477
50
-
half-life of activated, phosphorylated enzyme: 5 min, half-life of nonphosphorylated enzyme: 15 min
438654
50
-
in presence of 10% glycerol, all mutant enzymes are stable for at least 1 h
657679
50
-
50% loss of activity after 90 min, 80% loss of activity after 2 h, wild-type enzyme
660477
additional information
-
thermal stability of hTH1 is increased by phosphorylation at Ser-40
438708
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
0.1 M 2-mercaptoethanol is necessary for stabilization during purification
-
phosphorylated enzyme is less stable than nonphosphorylated form
-
binding of inhibitor dopamine and of cofactor tetrahydrobioterin stabilizes the enzyme
-
catecholamine binding improves tyrosine hydroxylase's resistance to proteolysis
-
the 14-3-3eta protein regulates tyrosine hydroxylase type 1 stability against degradation by acting on the N-terminus
-
enzyme is stabilized by immobilization on polyacrylamide-based support
-
EDTA, 0.1 mM stabilizes
-
glycerol, 25% stabilizes
-
heparin stabilizes
-
phosphorylated enzyme is less stable than nonphosphorylated form
-
Tween 80, 0.05% stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, in presence of diisopropylfluorophosphate, 2 months
-
-80C, highly purified enzyme, 2 months
-
-80C, protein concentration above 0.05 mg/ml, 2 months
-
4C, in presence of diisopropylfluorophosphate, 1 week
-
-80C, purified wild-type enzyme can be stored indefinetely in absence of glycerol. the mutant enzymes T245P and T463M behave similarly. The removal of glyceryl from the T283M and R306H enzymes results in significant precipitation and loss of the protein
-
-80C, 20 mM Tris-HCl, pH 7.4, 8% sucrose, dithiothreitol, several months
-
-30C, immobilized and lyophilized enzyme, stored in dry environment, unaltered more than 150 days
-
-80C, 0.05% Tween 80, 0.1 mM EDTA, 25% glycerol, 5 mM sodium phosphate buffer, pH 7.5, 3 months without loss of activity
-
-80C, 0.05% Tween 80, 1 mM EDTA, 25% glycerol, 3 months
-
4C, 24 h, 0.05% Tween 80, 1 mM EDTA, 25% glycerol, 68% loss of activity
-
4C, 5 h, without stabilizing agents, almost complete loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
heparin-Sepharose column chromatography, DEAE-Sepharose column chromatography, and Sephacryl S-200HR gel filtration
-
2 forms with different MW in adrenal medulla; from caudate nuclei
-
from adrenal medulla
-
from adrenal medulla; large scale
-
GST-Sepharose column chromatography
-
ammonium sulfate precipitation and Sephacryl S-300HR gel filtration
-
4 isoforms, recombinant from Escherichia coli
-
amylose resin column chromatography and HiPrep Q column chromatography
-
GST-Sepharose column chromatography
-
heparin Sepharose chromatography
-
Hi-TRAP heparin column
-
more than 90% homogeneity
-
Ni-chelating Sepharose fast flow bead chromatography
-
one chromatography step
-
recombinant His-tagged enzyme from Escherichia coli strain XL-1 Blue by nickel affinity chromatography and gel filtration
-
immobilization on polyacrylamide-based support
-
2 kinetically distinguishable forms of the enzyme: low Km form and high Km form; from brain
-
ammonium sulfate precipitation
-
heparin column chromatography and Superdex 200 gel filtration
-
heparin Sepharose chromatography, incubation with ferrous iron, Q-Sepharose chromatography
-
Ni-affinity chromatography
-
recombinant
-
recombinant enzyme from Spodoptera frugiperda
-
recombinant from Escherichia coli
-
recombinant wild-type and mutants from Escherichia coli
-
the phosphorylated TyrH is purified by Q-Sepharose column chromatography
-
immobilized metal ion affinity chromatography (Ni2+)
-
recombinant from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) pLysS cells
-
expressed in Escherichia coli BL21(DE3)pLysS cells
-
expression Escherichia coli BL21(DE33)
-
expressed in SH-SY5Y, SK-N-BE(2), and IMR-32 cells
GQ403009
4 isoforms, overexpression in Escherichia coli, phosphorylation-free
-
DNA and amino acid sequence determination and analysis of wild-type enzyme and polymorphic genetic variants, expression in human chromaffin cells
-
enzyme expression by in vitro transcription-translation using a rapid translation system with enhanced Escherichia coli lysate and radio-labeled L-Met, tetrahydrobioterin increases the enzyme protein yield
-
expressed in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21(DE3) pLysS cells
-
expressed in monkey striatum using harmless adeno-associated virus vectors and in PC-12 cells and AtT-20 cells
-
expressed in SH-SY5Y cells
-
expressed in SH-SY5Y, SK-N-BE(2), and IMR-32 cells
GQ403014 and GQ403013 and GQ403012
expression in Escherichia coli
-
expression in Escherichia coli BL21(DE3)
-
expression in Escherichia coli BL21(DE3) as maltose-binding protein fusion protein
-
expression of gene fragment, comprising positions -495 to +25, which have regulatory promoter function, from a pGL-Basic luciferase reporter vector in MES23.5 cells and MES23.5 alpha-synuclein-overexpressing cells, alpha-synuclein is a negative regulator of the tyrosine hydroxylase expression via trans-acting function on the TH promoter, overview
-
isoform 1 hTH1 and His-tagged truncated mutant, expression in Escherichia coli
-
isozyme DNA and amino acid sequence determination and analysis, RT-PCR analysis of isozyme expression in neuroblastoma tumors, in abdominal and thoracic tumours and foetal adrenal glands, using external and internal primers, 4.0fold lower expression level in adrenal glands than in abdominal tumors, overview, expression of the enzyme mutant lacking exons 2, 8, and 9 in HeLa cells
-
expressed in SH-SY5Y, SK-N-BE(2), and IMR-32 cells
GQ403011
DNA and amino acid sequence determination and analysis, expression of His-tagged enzyme in Escherichia coli strain XL-1 Blue
-
expression of an enzyme-luciferase fusion protein in MN9D cells, quantitative PCR-based enzyme expression analysis, overview
-
expressed in SH-SY5Y, SK-N-BE(2), and IMR-32 cells
GQ403010
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21(DE3) pLysS cells
-
expression analysis
-
expression in Escherichia coli
-
expression in Escherichia coli BL21(DE3) as His-tag fusion protein
-
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 of wild-type and mutant enzymes in Escherichia coli
-
a His-tagged version expressed in Escherichia coli BL21 (DE3)
-
expression as His-tagged protein in Escherichia coli, amino acid sequence analysis
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the initial stress stage (for 10 min at 30C) is accompanied by an increase of the relative content of tyrosine hydroxylase-positive neurons in some central nervous system areas
-
striatal tyrosine hydroxylase shows a 49.8% reduction compared to control values in incidental Lewy body disease cases
-
the initial stress stage (for 10 min at 30C) is accompanied by an increase of the relative content of tyrosine hydroxylase-positive neurons in some central nervous system areas
-
20 mg/kg cocaine administration to neuronal nitric oxide synthase knockout mice significantly decreases striatal tyrosine hydroxylase expression
-
methamphetamine induces reduction of tyrosine hydroxylase
-
the amount of tyrosine hydroxylase protein in the brain of sepiapterin reductase-null mice is less than 10% of wild type, while tyrosine hydroxylase protein in the adrenal gland is not altered
-
tyrosine hydroxylase expression is unaffected by overexpression of wild type and phospho-mimic mutant alpha-synuclein (S129D)in dopaminergic MN9D cells, however, alpha-synuclein overexpression evidently inhibits TH phosphorylation at Ser40, while alpha-synuclein (S129D) mutant enhances phosphorylation
-
20 mg/kg cocaine administration to wild type mice significantly increases striatal tyrosine hydroxylase expression
-
although minocycline increases tyrosine hydroxylase-immunoreactivity in glial cell line-derived neurotrophic factor+/- mice, it does not attenuate the methamphetamine-induced reduction of tyrosine hydroxylase
-
atipamezole and/or levodopa treatments do not clearly affect on the amount of tyrosine hydroxylasein the striatum
-
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.
-
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.
-
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
-
in cercaria compared with the adult worm
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E434A
-
the mutant shows 35.6% of wild type activity. Furthermore, the mutation dramatically reduces its substrate affinity for tetrahydrobiopterin and decreases its activation by Fe2+
A297L
-
outer edge of the active site
A297L
-
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
D361N
-
reductions in Vmax are not significantly different from the wild type enzyme
E332A
-
the mutant has 10fold higher Km for 6-methyltetrahydropterin, but reduction of the enzyme by 6-methyltetrahydropterin is similar to the wild type
E332D
-
active site residue, 10fold reduction in activity, close to the catalytic iron
E332Q
-
active site residue, no activity, close to the catalytic iron
E362G
-
the Vmax is reduced compared to the wild type enzyme
E362Q
-
reductions in Vmax are not significantly different from the wild type enzyme
E362R/E365R
-
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
E365G
-
the Vmax is reduced compared to the wild type enzyme
E365Q
-
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
F184W/W372F
-
4fold lower Km for L-tyrosine compared to the wild-type enzyme. Similar Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
F300A
-
active site residue
F300Y
-
active site residue
K170E/L480A
-
the mutant is inhibited over the same range of dopamine like the wild type enzyme
K366L
-
reductions in Vmax are not significantly different from the wild type enzyme
L205P
-
the mutant is associated with recessively inherited L-DOPA-responsive infantile parkinsonism, the mutation reduces the activity and stability of the protein in cells and in vitro expression systems, being considered a misfolding mutation
L294A
-
protrudes into catalytic cleft
R306H
-
1.2fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, Ki-value for L-tyrosine is nearly identical to wild-type value, 1.3fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.2fold increase of turnover-number compared to wild-type enzyme. 8.2C increase in Tm-value compared to wild-type enzyme
R306H/T463M
-
all of the TyrH is insoluble and no enzyme can be purified
R37E/R38E
-
the point mutation increases the binding capacity of 5,6,7,8,-tetrahydrobiopterin to tyrosine hydroxylase molecule to increase the activity and possibly to increase the stability
R37E/R38E
-
the KM for tetrahydrobiopterin measured for the mutant is approximately half that of the wild type enzyme and the Vmax is significantly less reduced by dopamine than for the wild type enzyme
S368A
-
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
S40E
-
the mutant mimics a phosphorylation of S40. The kinetics of reduction and oxidation of the enzyme are similar to the wild type
T245P
-
1.4fold increase in Km-value for L-tyrosine compared to wild-type enzyme, 1.6fold increase in Ki-value for L-tyrosine compared to wild-type enzyme, 1.1fold increase in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.6fold increase of turnover-number compared to wild-type enzyme. 3.9C increase in Tm-value compared to wild-type enzyme
T245P/T283M
-
all of the TyrH is insoluble and no enzyme can be purified
T283M
-
1.2fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, 1.2fold decrease in Ki-value for L-tyrosine compared to wild-type enzyme, 1.3fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 4.2fold decrease of turnover-number compared to wild-type enzyme
T463M
-
1.1fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, Ki-value for L-tyrosine is nearly identical to wild-type value compared to wild-type enzyme, 1.4fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.2fold increase of turnover-number compared to wild-type enzyme. 7.7C increase in Tm-value compared to wild-type enzyme
W166F/F184W/W233F/W372F
-
mutant protein contains one tryptophan at residue 184 in the middle of a mobile active-site loop. The mutant was generated to perform steady-state fluorescence anisotropy measurements and shows kinetic properties similar to the wild-type enzyme
W166F/F184W/W372F
-
Km for L-tyrosine similar to the wild-type enzyme. 3fold higher Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
W166F/W233F/W372F
-
Km for L-tyrosine similar to the wild-type enzyme. 4fold higher Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
W166F/W372F
-
Km for L-tyrosine similar to the wild-type enzyme. 3fold higher Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
W372F
-
10fold lower Km for L-tyrosine compared to the wild-type enzyme. Similar Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to 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
-
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
D425W
-
inactive
D425Y
-
the mutant shows strongly reduced activity compared to the wild type enzyme
DELTA1-120
-
not inhibited by dopamine
DELTA1-32
-
90% inhibited by dopamine
DELTA1-68
-
not inhibited by dopamine
DELTA1-76
-
not inhibited by dopamine
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
H323Y
-
enhanced Km for tyrosine, 4.5fold enhanced phenylalanine hydroxylation activity, active site mutant
H331E
-
iron content is not significantly altered
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
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
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 42C in presence of 2% glycerol
S19E
-
mimics phosphorylation at S19
S19E
-
investigation of regulation by phosphorylation
S19E/S40E
-
mimics phosphorylation at S19S40
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 42C in presence of 2% glycerol
S31E
-
mimics phosphorylation at S31
S31E
-
good mimic of phosphorylated wild type protein
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
-
inactivated 1.6fold faster than the wild-type enzyme at 42C in presence of 2% glycerol
S40E
-
mimics phosphorylation at S40
S40E
-
good mimic of phosphorylated wild type protein
S8E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. More stable than wild-type enzyme at 42C in presence of 2% glycerol
S8E
-
mimics phosphorylation at S8
S8E
-
investigation of regulation by phosphorylation
T427A
-
the mutant shows reduced activity compared to the wild type enzyme
W166F/W233F/W372F
-
tryptophan-free enzyme with wild-type activity
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
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
L294Y
-
protrudes into catalytic cleft
additional information
-
truncated hTH1 isoform lacking the 150 N-terminal amino acids
additional information
-
construction of a truncation enzyme mutant lacking exons 2, 8, and 9 and showing reduced enzyme activity
additional information
-
detection of single nucleotide polymorphisms in the local genomic region, systematic polymorphism discovery at the TH locus and analysis for contributions to sympathetic function and blood pressure, i.e. 4 common TH promoter polymorphisms C-824T, G-801C, A-581G, and G-494A, overview
additional information
-
deletion of the N-terminus of tyrosine hydroxylase removes the high affinity dopamine binding site, but does not affect dopamine binding to the low affinity site
additional information
-
the deletion mutation of N-terminal 38-amino acids increases the binding capacity of 5,6,7,8,-tetrahydrobiopterin to tyrosine hydroxylase molecule to increase the activity and possibly to increase the stability
Y371F
-
active site residue, close to the catalytic iron
additional information
-
construction of neurokinin 3 receptor knockout mice, the mutant mice do not show altered tyrosine hydroxylase levels in the caudate putamen or nucleus accumbens, but show decreased enzyme levels in the olfactory tuberculum, phenotype, overview
additional information
-
increased TH-Ser40 phosphorylation in primary mesencephalic dopaminergic neurons from PKCdelta knock-out mice, overview
additional information
-
reduction of high-level tyrosine hydroxylase dopaminergic alpha-Syn-deficient cells by infection with wild-type alpha-Syn human lentivirus, overview
additional information
-
silencing alpha-synuclein gene expression by short hairpin RNA expression does not affect tyrosine hydroxylase expression but enhance tyrosine hydroxylase activity in MN9D cells by increasing TH Ser40 phosphorylation, overview
additional information
-
the pogo/pogo mouse phenotype of ataxic mice shows upregulation of tyrosine hydroxylase expression induced by enzyme phosphorylation via cyclin-dependent kinase 5, reduced Cdk5 activity in both p35-/- and p39-/- cerebellum do not correspond to defects in tyrosine hydroxylase expression, overview
additional information
Mus musculus C57BL/6J
-
silencing alpha-synuclein gene expression by short hairpin RNA expression does not affect tyrosine hydroxylase expression but enhance tyrosine hydroxylase activity in MN9D cells by increasing TH Ser40 phosphorylation, overview
-
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
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
-
tyrosine hydroxylase is frequently used as a marker of dopaminergic neuronal loss in animal models of Parkinsons disease
synthesis
-
immobilization of tyrosinase on polyacrylamide-based support for production of L-dopa from L-tyrosine thereby modifying the enzyme activity to tyrosine hydroxylase
analysis
-
the enzyme is useful for determination of neuronal loss after brain treatment with neurotoxic compounds, overview