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Information on EC 1.14.16.4 - tryptophan 5-monooxygenase and Organism(s) Rattus norvegicus and UniProt Accession Q8CGU9
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1.14.16.4 tryptophan 5-monooxygenaseIUBMB Comments
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
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Word Map
- 1.14.16.4
- serotonin
-
serotonergic
-
raphe
- 5-hydroxytryptamine
-
monoamine
-
dorsal
- dopamine
-
neurotransmitter
- hippocampus
-
antidepressant
-
reuptake
- 5-hydroxytryptophan
-
anxiety
-
psychiatric
- midbrain
- striatum
- hypothalamus
-
neurochemical
-
5-hydroxyindoleacetic
-
mood
-
enterochromaffin
-
neurotransmission
-
5-hiaa
- p-chlorophenylalanine
- fluoxetine
-
pineal
- brainstem
- alpha-methyl-p-tyrosine
-
monoaminergic
-
5,7-dihydroxytryptamine
- analysis
- methamphetamine
-
autoreceptors
-
slc6a4
-
immobility
- pargyline
- n-acetylserotonin
- neostriatal
-
5-httlpr
- medicine
- citalopram
-
antidepressant-like
- carcinoid
- biopterins
-
impulsivity
-
oxidase-a
- tetrahydropterins
- fenfluramine
-
impulsive
-
8-oh-dpat
- 5-hydroxyindole
- drug development
- 3,4-methylenedioxymethamphetamine
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
+
=
+
+
+
=
+
a 4a-hydroxy-5,6,7,8-tetrahydropteridine
Synonyms
tryptophan hydroxylase, tryptophan hydroxylase 2, tryptophan hydroxylase 1, tph-1, tryptophan hydroxylase-2, tryptophan hydroxylase-1, tph-2, tryptophan-5-hydroxylase, tryptophan 5-monooxygenase, htph2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
indoleacetic acid-5-hydroxylase
-
-
-
-
L-tryptophan hydroxylase
-
-
-
-
oxygenase, tryptophan 5-mono-
-
-
-
-
tryptophan 5-hydroxylase
-
-
-
-
tryptophan hydroxylase
tryptophan hydroxylase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
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oxidation
-
-
-
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reduction
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-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
CAS REGISTRY NUMBER
COMMENTARY
9037-21-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
-
tryptophan hydroxylase form I, 39% of activity with L-tryptophan
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + 2-amino-4-hydroxy-6-methyl-tetrahydropteridine + O2
?
-
-
-
-
r
L-tryptophan + 6-methyl-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in 5-hydroxytryptamine, i.e. serotonin, biosynthesis in the brain, and is a candidate for participation in a mechanism mediating the antidepressant effect of selective 5-hydroxytryptamine reuptake inhibitors such as fluoxetine, TPH2 gene expression in the midbrain part of the dorsal raphenucleus is implicated in depression and stress response
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
1.3fold activity compared to the human tryptophan hydroxylase 2
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
isozyme TPH2 is the rate-limiting enzyme in serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
the calcium influx through L-type high voltage-activated calcium channels is essential for the full activation of tryptophan hydroxylase leading to melatonin synthesis in the pineal gland
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
the enzyme is involved in emotional responses
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is involved in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, important neurotransmitters in the brain and involved in regulation of body temperature, blood pressure, endocrine activity, appetite, sexual behavior, movement, emesis, and pain, the enzyme activity plays a role in exercise-induced fatigue, overvieww
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is the rate limiting enzyme in serotonin biosynthesis, the enzyme and 5-hydroxytryptamine might be involved in exercise-induced fatigue
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
rate-limiting enzyme in synthesis of 5-hydroxy-L-tryptophan
-
-
?
additional information
?
-
the enzyme expression in brain is correlated to glucocorticoid fluctuations, e.g. corticosterone, overview
-
-
?
additional information
?
-
TPH2 expression is part of the developmental program regulated by REST, i.e. the RE-1 silencer of transcription, REST/NRSF is implicated in neurogenesis and transcriptionally regulates a network of genes, overview
-
-
?
additional information
?
-
-
chronic treatment with milnacipran or fluvoxamine is effective to improve both the hyperemotional behavior and the loss of TPH-positive cells in olfactory bulbectomized rats, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in 5-hydroxytryptamine, i.e. serotonin, biosynthesis in the brain, and is a candidate for participation in a mechanism mediating the antidepressant effect of selective 5-hydroxytryptamine reuptake inhibitors such as fluoxetine, TPH2 gene expression in the midbrain part of the dorsal raphenucleus is implicated in depression and stress response
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
isozyme TPH2 is the rate-limiting enzyme in serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
the calcium influx through L-type high voltage-activated calcium channels is essential for the full activation of tryptophan hydroxylase leading to melatonin synthesis in the pineal gland
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
the enzyme is involved in emotional responses
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is involved in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, important neurotransmitters in the brain and involved in regulation of body temperature, blood pressure, endocrine activity, appetite, sexual behavior, movement, emesis, and pain, the enzyme activity plays a role in exercise-induced fatigue, overvieww
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is the rate limiting enzyme in serotonin biosynthesis, the enzyme and 5-hydroxytryptamine might be involved in exercise-induced fatigue
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
rate-limiting enzyme in synthesis of 5-hydroxy-L-tryptophan
-
-
?
additional information
?
-
the enzyme expression in brain is correlated to glucocorticoid fluctuations, e.g. corticosterone, overview
-
-
?
additional information
?
-
TPH2 expression is part of the developmental program regulated by REST, i.e. the RE-1 silencer of transcription, REST/NRSF is implicated in neurogenesis and transcriptionally regulates a network of genes, overview
-
-
?
additional information
?
-
-
chronic treatment with milnacipran or fluvoxamine is effective to improve both the hyperemotional behavior and the loss of TPH-positive cells in olfactory bulbectomized rats, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Fe2+
Ca2+
-
the calcium influx through L-type high voltage-activated calcium channels is essential for the full activation of tryptophan hydroxylase leading to melatonin synthesis in the pineal gland
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-amino-5-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)pent-4-ynoic acid
-
-
(3R)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
(3S)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
(3S)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
2-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,6-diazaspiro[3.4]octane-7-carboxylic acid
-
-
3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-N-(2-methylprop-2-en-1-yl)-3-azabicyclo[3.2.1]octan-8-amine
-
-
3-amino-3-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperidin-4-yl]propanoic acid
-
-
3-[(3R)-3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)pyrrolidin-1-yl]-L-alanine
-
-
3-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperidin-4-yl]propanoic acid
-
-
3-[3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-L-alanine
-
-
3-[3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-L-alanine
-
-
3-[4-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-1,4-diazepan-1-yl]-L-alanine
-
-
3-[4-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperazin-1-yl]-L-alanine
-
-
3-[5-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl]-L-alanine
-
-
3-[6-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl]-L-alanine
-
-
3-[8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-L-alanine
-
-
4-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-6-[4-[(2H-tetrazol-5-yl)amino]piperidin-1-yl]pyrimidin-2-amine
-
-
7-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonane-3-carboxylic acid
-
-
8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-1,8-diazaspiro[4.5]decane-2-carboxylic acid
-
-
8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(4-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(4-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(5-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyridazin-3-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(5-[(1S)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrazin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-hydroxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-methylpyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-phenoxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrazin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
8-[6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-(cyclohexylamino)pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
-
-
9-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,9-diazaspiro[5.5]undecane-2-carboxylic acid
-
-
ethyl (3S)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate
-
-
N-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,5-dimethylpiperidin-4-yl]glycine
-
-
N-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-4-methylpiperidin-4-yl]glycine
-
-
N-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperidin-4-yl]glycine
-
-
N-[4-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)phenyl]methanesulfonamide
-
-
nifedipine
-
reduces the enzyme activity by blocking the Ca2+-influx accompanied with a reduction of 5-hydroxytryptophan, serotonin, N-acetylserotonin and melatonin intracellular content, as well as a reduction of serotonin and melatonin secretion
additional information
glucocorticoids inhibits TPH2 expression, the suppression is blocked by mifepristone, i.e. RU-486
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
fluoxetine treatment for 4 and 8 weeks significantly increases basal TPH2 mRNA levels in the midbrain, correlated with the appearance of antidepressant-like effects in the forced swim test, co-induction of TPH2 and the 5-hydroxytryptamine transporter expression, overview
-
additional information
TPH2 is upregulated by dominant-negative RE-1 silencer of transcription, minimum of 4.4fold relative to hypoxanthine-guanine phosphoribosyltransferase, overview
-
additional information
-
Acanthopanax senticosus, as aqueous extracts from fresh stem braks, increases the time to exhaustion by treadmill running and it suppressed the exercise-induced increase of 5-hydroxytryptamine synthesis and TPH expression. Acanthopanax senticosus is effective as caffeine for increasing the exhaustion time in treadmill running and for reducing the exercise-induced increase of 5-hydroxytryptamine synthesis and TPH expression in the dorsal raphe, overview
-
additional information
-
administration of 3,4-methylenedioxymethamphetamine to rats induces TPH1, but affects serotonin biosynthesis and TPH enzyme activity in dorsal raphe nuclei, and it decreases SERT binding sites in the striatum, nucleus accumbens and cingulate cortex demonstrating a loss of 5-hydroxytryptamine terminals, overview
-
additional information
-
in differentiated RN46A cells, the TPH2 promoter is induced 2.5fold by ionomycin, similar to its action on TPH2 RNA. By contrast, ionomycin has no effect onTPH2 promoter activity in GH4C1 cells or TPH2-negative L6 myoblasts, overview
-
additional information
-
the calcium influx through L-type high voltage-activated calcium channels is essential for the full activation of tryptophan hydroxylase leading to melatonin synthesis in the pineal gland
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the KM-value of TrpOH in the cerebral cortex and in the brainstem from diabetic rates are significantly increased when compared to those from control rats
-
0.125
2-amino-4-hydroxy-6-methyltetrahydropteridine
-
tryptohan hydroxylase form I
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
(2S)-2-amino-5-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)pent-4-ynoic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.001787
(3R)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000026
(3S)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000871
(3S)-8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.02
2-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,6-diazaspiro[3.4]octane-7-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000361
3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-N-(2-methylprop-2-en-1-yl)-3-azabicyclo[3.2.1]octan-8-amine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.001019
3-amino-3-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperidin-4-yl]propanoic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.002149
3-[(3R)-3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)pyrrolidin-1-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.002714
3-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperidin-4-yl]propanoic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00622
3-[3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000096
3-[3-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000211
3-[4-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-1,4-diazepan-1-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00005
3-[4-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperazin-1-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000449
3-[5-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.004039 - 0.005126
3-[6-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl]-L-alanine
0.000519
3-[8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.007552
4-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-6-[4-[(2H-tetrazol-5-yl)amino]piperidin-1-yl]pyrimidin-2-amine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.008536
7-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.005257
8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-1,8-diazaspiro[4.5]decane-2-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000055
8-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.002266
8-(4-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.002961
8-(4-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00593
8-(5-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyridazin-3-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.003422
8-(5-[(1S)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrazin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000583
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-hydroxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000065
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-methylpyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000128
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-phenoxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.02
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrazin-2-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000211
8-(6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000079 - 0.000159
8-[6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-(cyclohexylamino)pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
0.000949
9-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,9-diazaspiro[5.5]undecane-2-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00105
N-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,5-dimethylpiperidin-4-yl]glycine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.001407
N-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-4-methylpiperidin-4-yl]glycine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.001511
N-[1-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)piperidin-4-yl]glycine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.001355
N-[4-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)phenyl]methanesulfonamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.004039
3-[6-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.005126
3-[6-(2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl]-L-alanine
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000079
8-[6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-(cyclohexylamino)pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000159
8-[6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-(cyclohexylamino)pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
Rattus norvegicus
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.367
0.374
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.6
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus and in the brainstem containing the rest of the raphe complex
TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus and in the brainstem containing the rest of the raphe complex
-
ventral horn, enzyme expression in muscle after exercise-induced fatigue and control muscle, overview
additional information
circadian expression of TPH in dorsal and median raphe in correlation to glucocorticoid fluctuations, e.g. corticosterone, expression pattern, overview
in raphe nuclei, in lateral hypothalamic nuclei and in pineal body
-
dorsal raphe nucleus, expression analysis and enzyme levels of TPH2, quantitative immunoautoradiography and in situ hybridization histochemistry, overview, activity occurs also in striatum, nucleus accumbens and cingulate cortex
additional information
analysis of TPH2 expression in brain tissues, overview
additional information
-
olfactory bulbectomized rats, i.e. OBX rats, with olfactory bulbs removed by suction, no significant difference in the effects on TPH immunoreactivity in the median raphe of OBX rats between vehicle- and antidepressants-treated animals
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TPH2_RAT
485
0
55621
Swiss-Prot
Mitochondrion (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
288000
300000
59000
-
4 * 59000, tryptophan hydroxylase form I from brain stem, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
tetramer
-
4 * 59000, tryptophan hydroxylase form I from brain stem, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
polymorphism rs11178997 of the TPH2 promoter significantly reduces TPH2 transcriptional activity by 22% in primary serotonergic neurons. In contrast, no significant differences in promoter activity are observed for the G- and T-alleles of rs4570625. Reduced binding of the transcription factor POU3F2, i.e. Brn-2 or N-Oct-3, to the A-allele occur with the polymorphism rs11178997, while overexpression of POU3F2 results in a robust activation of the TPH2 promoter by about 2.7fold. The human TPH2 promoter is active in rat serotonergic raphe neurons
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
tryptophan hydroxylase form I and II, pH 4.8, ammonium sulfate, gel filtration, DEAE-Sepharose, 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine-agarose
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene TPH2, DNA and amino acid sequence determination, analysis of the TPH2 promoter and bipartite NRSE motif, a transcription element in the TPH2 promoter, a bipartite variant interrupted by a 6-base insertion, that resembles the binding motif for RE-1 silencer of transcription, i.e. REST, also known as NRSF transcription factor, quantitative reverse transcription-PCR expression analysis, sequence comparisons
transcriptional activity of the rat TPH2 promoter in GH4C1 cells, RN46A cells, and L6 myoblasts, overview
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kaufman, S.
Aromatic amino acid hydroxylases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
18
217-282
1987
Bos taurus, Canis lupus familiaris, Oryctolagus cuniculus, Rattus norvegicus
-
Koizumi, S.; Matsushima, Y.; Nagatsu, T.; Linuma, H.; Takeuchi, T.; Umezawa, H.
3,4-Dihydroxystyrene, a novel microbial inhibitor for phenylalanine hydroxylase and other pteridine-dependent monooxygenases
Biochim. Biophys. Acta
789
111-118
1984
Rattus norvegicus
Fujisawa, H.; Nakata, H.
Tryptophan 5-monooxygenase from rat brain stem
Methods Enzymol.
142
83-87
1987
Rattus norvegicus
Nakata, H.; Fujisawa, H.
Simple and rapid purification of tryptophan 5-monooxygenase from rabbit brain by affinity chromatography
J. Biochem.
90
567-569
1981
Oryctolagus cuniculus, Rattus norvegicus
Nakata, H.; Fujisawa, H.
Purification and properties of tryptophan 5-monooxygenase from rat brain-stem
Eur. J. Biochem.
122
41-47
1982
Rattus norvegicus
Cash, C.D.; Vayer, P.; Mandel, P.; Maitre, M.
Tryptophan 5-hydroxylase. Rapid purification from whole rat brain and production of a specific antiserum
Eur. J. Biochem.
149
239-245
1985
Rattus norvegicus
Joh, T.H.; Shikimi, T.; Pickel, V.M.; Reis, D.J.
Brain tryptophan hydroxylase: purification of, production of antibodies to, and cellular and ultrastructural localization in serotonergic neurons of rat midbrain
Proc. Natl. Acad. Sci. USA
72
3575-3579
1975
Rattus norvegicus
Park, D.H.; Stone, D.M.; Kim, K.S.; Joh, T.H.
Characterization of recombinant mouse tryptophan hydroxylase expressed in Escherichia coli
Mol. Cell. Neurosci.
5
87-93
1994
Mus musculus, Rattus norvegicus
Khan, I.A.; Thomas, P.
Aroclor 1254 inhibits tryptophan hydroxylase activity in rat brain
Arch. Toxicol.
78
316-320
2004
Rattus norvegicus
Herrera, R.; Manjarrez, G.; Hernandez, J.
Inhibition and kinetic changes of brain tryptophan-5-hydroxylase during insulin-dependent diabetes mellitus in the rat
Nutr. Neurosci.
8
57-62
2005
Rattus norvegicus
Zhang, X.; Beaulieu, J.M.; Gainetdinov, R.R.; Caron, M.G.
Functional polymorphisms of the brain serotonin synthesizing enzyme tryptophan hydroxylase-2
Cell. Mol. Life Sci.
63
6-11
2006
Danio rerio, Gallus gallus, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Hong, K.W.; Sugawara, Y.; Hasegawa, H.; Hayasaka, I.; Hashimoto, R.; Ito, S.; Inoue-Murayama, M.
A new gain-of-function allele in chimpanzee tryptophan hydroxylase 2 and the comparison of its enzyme activity with that in humans and rats
Neurosci. Lett.
412
195-200
2007
Callithrix jacchus, Gorilla gorilla, Homo sapiens, Macaca fuscata, Pan troglodytes, Pongo pygmaeus, Rattus norvegicus, Cephalopachus bancanus, Otolemur crassicaudatus, Hylobates agilis, Mandrillus sphinx
Scheuch, K.; Lautenschlager, M.; Grohmann, M.; Stahlberg, S.; Kirchheiner, J.; Zill, P.; Heinz, A.; Walther, D.J.; Priller, J.
Characterization of a functional promoter polymorphism of the human tryptophan hydroxylase 2 gene in serotonergic raphe neurons
Biol. Psychiatry
62
1288-1294
2007
Homo sapiens, Rattus norvegicus (Q8CGU9)
Malek, Z.S.; Sage, D.; Pevet, P.; Raison, S.
Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity
Endocrinology
148
5165-5172
2007
Rattus norvegicus (Q8CGU9)
Patel, P.D.; Bochar, D.A.; Turner, D.L.; Meng, F.; Mueller, H.M.; Pontrello, C.G.
Regulation of tryptophan hydroxylase-2 gene expression by a bipartite RE-1 silencer of transcription/neuron restrictive silencing factor (REST/NRSF) binding motif
J. Biol. Chem.
282
26717-26724
2007
Rattus norvegicus (Q8CGU9), Homo sapiens (Q8IWU9), Homo sapiens
Rhim, Y.T.; Kim, H.; Yoon, S.J.; Kim, S.S.; Chang, H.K.; Lee, T.H.; Lee, H.H.; Shin, M.C.; Shin, M.S.; Kim, C.J.
Effect of Acanthopanax senticosus on 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of exercised rats
J. Ethnopharmacol.
114
38-43
2007
Rattus norvegicus
Lenicov, F.R.; Lemonde, S.; Czesak, M.; Mosher, T.M.; Albert, P.R.
Cell-type specific induction of tryptophan hydroxylase-2 transcription by calcium mobilization
J. Neurochem.
103
2047-2057
2007
Rattus norvegicus, Homo sapiens (Q8IWU9)
Barbosa, R.; Scialfa, J.H.; Terra, I.M.; Cipolla-Neto, J.; Simonneaux, V.; Afeche, S.C.
Tryptophan hydroxylase is modulated by L-type calcium channels in the rat pineal gland
Life Sci.
82
529-535
2008
Rattus norvegicus
Clark, J.A.; Flick, R.B.; Pai, L.Y.; Szalayova, I.; Key, S.; Conley, R.K.; Deutch, A.Y.; Hutson, P.H.; Mezey, E.
Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice
Mol. Psychiatry
13
498-506
2008
Homo sapiens (Q8IWU9), Homo sapiens, Mus musculus, Mus musculus C57BL/6, Rattus norvegicus (Q8CGU9)
Xu, C.X.; Liu, H.T.; Wang, J.
Changes of 5-hydroxytryptamine and tryptophan hydroxylase expression in the ventral horn of spinal cord
Neurosci. Bull.
24
29-33
2008
Rattus norvegicus
Shishkina, G.T.; Kalinina, T.S.; Dygalo, N.N.
Up-regulation of tryptophan hydroxylase-2 mRNA in the rat brain by chronic fluoxetine treatment correlates with its antidepressant effect
Neuroscience
150
404-412
2007
Rattus norvegicus (Q8CGU9)
Bonkale, W.L.; Austin, M.C.
3,4-Methylenedioxymethamphetamine induces differential regulation of tryptophan hydroxylase 2 protein and mRNA levels in the rat dorsal raphe nucleus
Neuroscience
155
270-276
2008
Rattus norvegicus
Saitoh, A.; Yamaguchi, K.; Tatsumi, Y.; Murasawa, H.; Nakatani, A.; Hirose, N.; Yamada, M.; Yamada, M.; Kamei, J.
Effects of milnacipran and fluvoxamine on hyperemotional behaviors and the loss of tryptophan hydroxylase-positive cells in olfactory bulbectomized rats
Psychopharmacology
191
857-865
2007
Rattus norvegicus
Goldberg, D.R.; De Lombaert, S.; Aiello, R.; Bourassa, P.; Barucci, N.; Zhang, Q.; Paralkar, P.; Valentine, J.; Zavadoski, W.
Discovery of spirocyclic proline tryptophan hydroxylase-1 inhibitors
Bioorg. Med. Chem. Lett.
26
1124-1129
2016
Rattus norvegicus
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