Information on EC 1.14.16.4 - tryptophan 5-monooxygenase

New: Word Map on EC 1.14.16.4
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.14.16.4
-
RECOMMENDED NAME
GeneOntology No.
tryptophan 5-monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
hydroxylation regiospecificity
-
L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
phenylalanine hydroxylase, EC 1.14.16.1 also catalyzes this reaction
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
serotonin and melatonin biosynthesis
-
-
Tryptophan metabolism
-
-
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-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
indoleacetic acid-5-hydroxylase
-
-
-
-
L-tryptophan hydroxylase
-
-
-
-
oxygenase, tryptophan 5-mono-
-
-
-
-
tryptophan 5-hydroxylase
-
-
-
-
tryptophan hydroxylase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9037-21-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
a planarian, gene TPH
UniProt
Manually annotated by BRENDA team
isozyme TPH1
UniProt
Manually annotated by BRENDA team
alcohol-dependent patients of Caucasian origin from southern Germany
UniProt
Manually annotated by BRENDA team
borderline patients
-
-
Manually annotated by BRENDA team
Caucasian individuals
UniProt
Manually annotated by BRENDA team
Caucasian subjects
UniProt
Manually annotated by BRENDA team
depressive patients, gene TPH2
UniProt
Manually annotated by BRENDA team
enzyme from a carcinoid tumor
-
-
Manually annotated by BRENDA team
gene TPH2
UniProt
Manually annotated by BRENDA team
genes tph1 and tph2
UniProt
Manually annotated by BRENDA team
Han Chinese subjects, gene TPH1 encodes isozyme TPH1
UniProt
Manually annotated by BRENDA team
Han Chinese subjects, gene TPH2 encoding isozyme TPH2
UniProt
Manually annotated by BRENDA team
healthy persons and affective disorder patients from Germany and Russia
UniProt
Manually annotated by BRENDA team
isozyme TPH1; isozyme TPH1
UniProt
Manually annotated by BRENDA team
isozyme TPH1; isozyme TPH2
-
-
Manually annotated by BRENDA team
isozyme TPH2
UniProt
Manually annotated by BRENDA team
isozyme TPH2; isozyme TPH2
UniProt
Manually annotated by BRENDA team
isozymes TPH1 and TPH2
-
-
Manually annotated by BRENDA team
isozymes TPH1 and TPPH2
-
-
Manually annotated by BRENDA team
Japanese individuals
-
-
Manually annotated by BRENDA team
Korean subjects with major depressive disorder
UniProt
Manually annotated by BRENDA team
North European Caucasians, healthy persons and major depression patients, isozyme TPH2
UniProt
Manually annotated by BRENDA team
patients with major depression, gene TPH1
UniProt
Manually annotated by BRENDA team
TPH1; North European Caucasians, healthy persons and major depression patients, isozyme TPH1
UniProt
Manually annotated by BRENDA team
C57-albino male mice
-
-
Manually annotated by BRENDA team
C57/BL6 mice
-
-
Manually annotated by BRENDA team
C57Bl/6, 129X1/SvJ, DBA/2, and BALB/cJ mice, genes Tph1 and Tph2 encoding isozymes TPH1 and TPH2, respectively
-
-
Manually annotated by BRENDA team
DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele, and C57BL/6J and C57BL/6N mice carrying the 1473C allele
-
-
Manually annotated by BRENDA team
F2 hybrids of strains C57BL/6 and CC57BR
SwissProt
Manually annotated by BRENDA team
isozymes TPH1 and TPH2
-
-
Manually annotated by BRENDA team
male C57BL/6 mice
-
-
Manually annotated by BRENDA team
mastocytoma cell line P-815
-
-
Manually annotated by BRENDA team
senescence-accelerated prone mouse 6, i.e. SAMP6
-
-
Manually annotated by BRENDA team
TPH1; isozyme TPH1
UniProt
Manually annotated by BRENDA team
TPH2; isozyme TPH2
SwissProt
Manually annotated by BRENDA team
transgenic mice containing exon 1 of the human huntigton gene
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57/BL6 mice
-
-
Manually annotated by BRENDA team
no activity in Rattus norvegicus
PC-12 cells
-
-
Manually annotated by BRENDA team
female Spargue-Dawley rats
UniProt
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
male Wistar rats
UniProt
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
sp. scombroidei, yellofin tuna
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
serveral single nucleotide polymorphisms are associated with depression, suicidal behavior and bipolar disorder
malfunction
-
enzyme-deficient mice have elevated serum tryptophan levels, a normal mast cell compartment and enhanced signaling of mammalian target of rapamycin. Enzyme deficiency exacerbates experimental autoimmune encephalomyelitis
metabolism
-
rate-limiting enzyme in the serotonin biosynthesis
physiological function
-
TPH is a major site of hypoxia-induced down-regulation of serotonergic function in croaker brains
physiological function
-
the enzyme is a potent regulator of immunity regulating immune tolerance and inflammation. The enzyme is essential for the generation of protective T cellmediated antitumor immunity
physiological function
-
the th2 gene product is required for the synthesis of serotonin in vivo and has tryptophan hydroxylase activity in vitro
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-azaisotryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-2-azaisotryptophan + 6-hydroxy-2-azaisotryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
4-azatryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-4-azatryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
4-methyltryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-4-methyltryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
5-methyltryptophan + 6-methyltetrahydropterin + O2
5-hydroxymethyltryptophan + 5-hydroxy-4-methyltryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
more than 99% 5-hydroxymethyltryptophan
?
6-azatryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-6-azatryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
6-methyltryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-6-methyltryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
7-azatryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-7-azatryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
7-methyltryptophan + 6-methyltetrahydropterin + O2
5-hydroxy-7-methyltryptophan + 6-methyldihydropterin + H2O
show the reaction diagram
-
recombinant N- and C-terminal truncated enzyme
-
?
L-methionine + ? + O2
?
show the reaction diagram
-
relative high activity with pronase-treated PTMO
-
-
?
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
-
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
-
at a comparable rate of L-tryptophan hydroxylation
-
-
?
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
-
at a comparable rate of L-tryptophan hydroxylation
-
-
?
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
-
28.8% of the rate observed with L-tryptophan
-
?
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
-
tryptophan hydroxylase form I, 39% of activity with L-tryptophan
-
-
?
L-phenylalanine + tetrahydropteridine + O2
L-tyrosine + dihydropteridine + H2O
show the reaction diagram
-
purified PTMO shows no activity, relative high activity with pronase-treated PTMO
-
-
?
L-tryptophan + (6R)-L-erytho-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + ?
show the reaction diagram
P17752
-
-
-
?
L-tryptophan + (6R)-L-erytho-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + ?
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
over 300 single nucleotide polymorphisms have been identified and are associated with symptoms ranging from mild hyperphenylalaninemia to severe phenylketonuria
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
1.3fold activity compared to the human tryptophan hydroxylase 2
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan
show the reaction diagram
-
-
-
-
?
L-tryptophan + 6-methyl-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + 6-methyl-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + 6-methyl-tetrahydropterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydropterin
show the reaction diagram
-
-
-
-
-
L-tryptophan + 6-methyl-tetrahydropterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydropterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
-
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
synthetic construct
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17532, Q8CGV2
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGV2
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
A7VKD9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q2HZ26
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
A1Y9J6
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P70080
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
B3VBU9, B3VBV0
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
brain-specific isozyme TPH2 is the rate-limiting enzyme in serotonin biosynthesis, a truncated enzyme version occurs in brain tissues being the cause of impaired serotonin transmission
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
differences in the regulation of isozyme TPH2 versus isozyme TPH1, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
first and rate limiting step in the biosynthesis of the neurotransmitter serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P70080
first and rate-determining step in the biosynthesis of the neurotransmitter serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
first and rate-limiting step in serotonin biosynthesis, overview. Serotonin, i.e. 5-hydroxytryptamine, is a neurotransmitter that modulates central and peripheral functions through action on neurons, smooth muscle, and other cell types
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
first and rate-limiting step in serotonin biosynthesis, serotonin, i.e. 5-hydroxytryptamine, is a neurotransmitter with both central and peripheral functions, including the modulation of mood, appetite, hemodynamics, gastrointestinal sensation, secretion, and motility
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
initial and rate-limiting enzyme in the biosynthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
isozyme TPH2 is the rate-limiting enzyme in serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGV2
key enzyme of serotonin synthesis in the brain is tryptophan hydroxylase-2
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752
low tryptophan levels are associated with depression and may arise because of stress, the hypothalamic and peripheral serotonin, i.e.5-hydroxytryptamine-system has a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in serotonin biosynthesis, mice deficient in peripheral tryptophan hydroxylase and serotonin exhibit a reduced risk of thrombosis and thromboembolism
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
A1Y9J6
rate-limiting enzyme in serotonin synthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting step in serotonin, i.e. 5-hydroxytryptamine, biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
rate-limiting step in the biosynthesis of serotonin, regulation of isozymes TPH1 and TPH2, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
rate-limiting step in the synthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme is involved in emotional responses
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q2HZ26
the enzyme is involved in neuronal serotonin, i.e. 5-hydroxytryptamine, biosynthesis, genetic variance is associated with numerous behavioral traits and psychiatric disorders
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is rate limiting in serotonin biosynthesis and important in serotonergic neurotransmission, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
the enzyme is rate-limiting in neuronal serotonin biosynthesis, disturbances of the central serotonergic system, due to genetic variations in the TPH2 gene, are involved in the pathophysiology of alcohol dependence and suicidal behavior
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is rate-limiting in serotonin biosynthesis, deficient levels of serotonin are associated with suicide and depression
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
A7VKD9
the enzyme is required for serotonin, i.e. 5-hydroxytryptamine, biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17532, Q8CGV2
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain and serotonergic neuron development, also TPH1 is involved in behavioural disorders, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17532, Q8CGV2
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain and serotonergic neuron development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH is involved in 5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH is the rate limiting enzyme in serotonin biosynthesis, the enzyme and 5-hydroxytryptamine might be involved in exercise-induced fatigue
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH is the rate-limiting enzyme in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, possible involvement of the TPH1 218A allele in susceptibility to schizophrenia, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752
TPH1 is the rate-limiting enzyme in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
TPH2 control 5-hydroxytryptamine, i.e. serotonin, biosynthesis and its deficiency is involved in affective disorders, pathophysiological mechanism, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH2 is a rate-limiting enzyme of neuronal serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
TPH2 is involved in serotonin biosynthesis, which is involved in behavioural processes, e.g. working memory, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
TPH2 is rate-limiting in serotonin, i.e. 5-hydroxytryptamine, biosynthesis, serotonin is involved in the pathophysiology of several psychiatric disorders including major depression, MD, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
TPH2 is the first and rate-limiting enzyme in the serotonin biosynthetic pathway
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
TPH2 is the rate-limiting enzyme during 5-hydroxytryptamine synthesis in the brain
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
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
show the reaction diagram
-
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis, and polymorphisms of TPH2 are implicated in vulnerability to psychiatric disorders
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
relative high activity with pronase-treated PTMO
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Mus musculus C57BL/6
-
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
-
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
O96370
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor tetrahydrobiopterin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor tetrahydrobiopterin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
initial and uncommited step in the biosynthesis of melatonin
-
-
-
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
believed to be the rate-limeting enzyme in the biosynthesis of serotonin in the central nervous system
-
-
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
ovarian steroids stimulate TPH-2 mRNA expression, which can in turn cause an increase in serotonin synthesis
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
P17752
rate-determining step of serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
rate-limiting enzyme in synthesis of 5-hydroxy-L-tryptophan
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
rate-limiting step in biosynthesis of serotonin in brain
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
tryptophan hydroxylase-2 controls brain serotonin synthesis
-
-
?
L-tyrosine + tetrahydropteridine + O2
?
show the reaction diagram
-
1% of activity with L-tryptophan
-
-
?
L-tyrosine + tetrahydropteridine + O2
?
show the reaction diagram
-
relative high activity with pronase-treated PTMO
-
-
?
additional information
?
-
P17752, Q8IWU9
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview
-
-
-
additional information
?
-
P17752, Q8IWU9
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview, association of TPH1 with suicidal behavior, TPH1 is involved in brain and serotonergic neuron development, overview
-
-
-
additional information
?
-
Q8IWU9
additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing, serotonergic regulation of neural processing of affective stimuli with the striatum as a critical site where gene-gene regulation takes place, whole brain analysis for emotional word Stroop task, overview
-
-
-
additional information
?
-
-
alcohol consumption may influence TPH1 and TPH2 expression and regulation
-
-
-
additional information
?
-
P17752
association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population with major depressive disorder
-
-
-
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
-
-
-
additional information
?
-
-
emotional behavior and expression pattern tryptophan hydroxylase is altered in senescence-accelerated prone mouse 6, which show increased serotonin levels, overview
-
-
-
additional information
?
-
-
localized changes in TPH2 expression in specific subnuclei of the dorsal raphe nucleus suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus, overview
-
-
-
additional information
?
-
P17532, Q8CGV2
temporal expression pattern of TPH1 and pathway regulation, overview
-
-
-
additional information
?
-
P17532, Q8CGV2
temporal expression pattern of TPH2 and pathway regulation, overview
-
-
-
additional information
?
-
-
the borderline personality disorder might be partly due to serotonergic dysfunction
-
-
-
additional information
?
-
Q8CGU9
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
?
-
-
TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in major depression disorder, however, may not play a role in impulsive-aggressive behaviors as mediators, overview
-
-
-
additional information
?
-
-
no activity with L-tyrosine
-
-
-
additional information
?
-
-
pronase-treated PTMO shows less than 5% activity of that of L-phenylalanine for L-lysine, L-histidine and L-threonine
-
-
-
additional information
?
-
-
residue lying adjacent to substrate is F313, role of F313 in substrate specificity, residue is different from L-phenylalanine 4-hydroxylase
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
over 300 single nucleotide polymorphisms have been identified and are associated with symptoms ranging from mild hyperphenylalaninemia to severe phenylketonuria
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
brain-specific isozyme TPH2 is the rate-limiting enzyme in serotonin biosynthesis, a truncated enzyme version occurs in brain tissues being the cause of impaired serotonin transmission
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
differences in the regulation of isozyme TPH2 versus isozyme TPH1, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
first and rate limiting step in the biosynthesis of the neurotransmitter serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P70080
first and rate-determining step in the biosynthesis of the neurotransmitter serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
first and rate-limiting step in serotonin biosynthesis, overview. Serotonin, i.e. 5-hydroxytryptamine, is a neurotransmitter that modulates central and peripheral functions through action on neurons, smooth muscle, and other cell types
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
first and rate-limiting step in serotonin biosynthesis, serotonin, i.e. 5-hydroxytryptamine, is a neurotransmitter with both central and peripheral functions, including the modulation of mood, appetite, hemodynamics, gastrointestinal sensation, secretion, and motility
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
initial and rate-limiting enzyme in the biosynthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
isozyme TPH2 is the rate-limiting enzyme in serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGV2
key enzyme of serotonin synthesis in the brain is tryptophan hydroxylase-2
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752
low tryptophan levels are associated with depression and may arise because of stress, the hypothalamic and peripheral serotonin, i.e.5-hydroxytryptamine-system has a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting enzyme in serotonin biosynthesis, mice deficient in peripheral tryptophan hydroxylase and serotonin exhibit a reduced risk of thrombosis and thromboembolism
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
A1Y9J6
rate-limiting enzyme in serotonin synthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
rate-limiting step in serotonin, i.e. 5-hydroxytryptamine, biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
rate-limiting step in the biosynthesis of serotonin, regulation of isozymes TPH1 and TPH2, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
rate-limiting step in the synthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme is involved in emotional responses
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q2HZ26
the enzyme is involved in neuronal serotonin, i.e. 5-hydroxytryptamine, biosynthesis, genetic variance is associated with numerous behavioral traits and psychiatric disorders
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is rate limiting in serotonin biosynthesis and important in serotonergic neurotransmission, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
the enzyme is rate-limiting in neuronal serotonin biosynthesis, disturbances of the central serotonergic system, due to genetic variations in the TPH2 gene, are involved in the pathophysiology of alcohol dependence and suicidal behavior
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is rate-limiting in serotonin biosynthesis, deficient levels of serotonin are associated with suicide and depression
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
A7VKD9
the enzyme is required for serotonin, i.e. 5-hydroxytryptamine, biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17532, Q8CGV2
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain and serotonergic neuron development, also TPH1 is involved in behavioural disorders, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17532, Q8CGV2
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain and serotonergic neuron development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH is involved in 5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
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
show the reaction diagram
-
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH is the rate limiting enzyme in serotonin biosynthesis, the enzyme and 5-hydroxytryptamine might be involved in exercise-induced fatigue
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH is the rate-limiting enzyme in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, possible involvement of the TPH1 218A allele in susceptibility to schizophrenia, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752
TPH1 is the rate-limiting enzyme in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
TPH2 control 5-hydroxytryptamine, i.e. serotonin, biosynthesis and its deficiency is involved in affective disorders, pathophysiological mechanism, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH2 is a rate-limiting enzyme of neuronal serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
TPH2 is involved in serotonin biosynthesis, which is involved in behavioural processes, e.g. working memory, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
TPH2 is rate-limiting in serotonin, i.e. 5-hydroxytryptamine, biosynthesis, serotonin is involved in the pathophysiology of several psychiatric disorders including major depression, MD, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17752, Q8IWU9
TPH2 is the first and rate-limiting enzyme in the serotonin biosynthetic pathway
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8IWU9
TPH2 is the rate-limiting enzyme during 5-hydroxytryptamine synthesis in the brain
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
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
show the reaction diagram
-
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Q8CGU9
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis, and polymorphisms of TPH2 are implicated in vulnerability to psychiatric disorders
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
Mus musculus C57BL/6
-
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
initial and uncommited step in the biosynthesis of melatonin
-
-
-
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
enzyme catalyzes the rate-limiting step in biosynthesis of putative neurotransmitter 5-hydroxytryptamine, serotonin
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
believed to be the rate-limeting enzyme in the biosynthesis of serotonin in the central nervous system
-
-
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
ovarian steroids stimulate TPH-2 mRNA expression, which can in turn cause an increase in serotonin synthesis
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
P17752
rate-determining step of serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
rate-limiting enzyme in synthesis of 5-hydroxy-L-tryptophan
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
rate-limiting step in biosynthesis of serotonin in brain
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
-
tryptophan hydroxylase-2 controls brain serotonin synthesis
-
-
?
additional information
?
-
P17752, Q8IWU9
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview
-
-
-
additional information
?
-
P17752, Q8IWU9
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview, association of TPH1 with suicidal behavior, TPH1 is involved in brain and serotonergic neuron development, overview
-
-
-
additional information
?
-
Q8IWU9
additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing, serotonergic regulation of neural processing of affective stimuli with the striatum as a critical site where gene-gene regulation takes place, whole brain analysis for emotional word Stroop task, overview
-
-
-
additional information
?
-
-
alcohol consumption may influence TPH1 and TPH2 expression and regulation
-
-
-
additional information
?
-
P17752
association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population with major depressive disorder
-
-
-
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
-
-
-
additional information
?
-
-
emotional behavior and expression pattern tryptophan hydroxylase is altered in senescence-accelerated prone mouse 6, which show increased serotonin levels, overview
-
-
-
additional information
?
-
-
localized changes in TPH2 expression in specific subnuclei of the dorsal raphe nucleus suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus, overview
-
-
-
additional information
?
-
P17532, Q8CGV2
temporal expression pattern of TPH1 and pathway regulation, overview
-
-
-
additional information
?
-
P17532, Q8CGV2
temporal expression pattern of TPH2 and pathway regulation, overview
-
-
-
additional information
?
-
-
the borderline personality disorder might be partly due to serotonergic dysfunction
-
-
-
additional information
?
-
Q8CGU9
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
?
-
-
TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in major depression disorder, however, may not play a role in impulsive-aggressive behaviors as mediators, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
tetrahydrobiopterin
synthetic construct
-
-
tetrahydrobiopterin
P70080
-
tetrahydrobiopterin
-
-
tetrahydrobiopterin
B3VBU9, B3VBV0
;
tetrahydrobiopterin
-
;
tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
tetrahydrobiopterin
-
-
additional information
-
residue Y235 is involved in cofactor binding, residue is different from L-phenylalanine 4-hydroxylase
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
activates TPH2 promoter activity
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
Fe2+
-
enzyme from pineal gland, stimulation; some brain enzymes are stimulated others not
Fe2+
-
required for maximal activity
Fe2+
-
5fold increase in activity
Fe2+
-
0.02 mM, 3.5fold increase in activity
Fe2+
-
not required for full activity
Fe2+
-
stimulates in the absence of catalase
Fe2+
-
N- and C-terminal recombinant enzyme, iron is required for activity
Fe2+
-
recombinant pineal enzyme contains 0.2-0.3 mol of iron/mol of enzyme
Fe2+
-
Fe2+ concentration for half-maximal activation of recombinant N-terminal truncated enzyme: 0.0013 mM
Fe2+
-
required for activity
Fe2+
P70080
the iron coordination is a distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 A between the iron and the tryptophan Czeta3 atom that is hydroxylated
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(6R)-5,6,7,8-tetrahydrobiopterin
-
-
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH2, substrate inhibition
(7R)-5,6,7,8-tetrahydrobiopterin
-
recombinant pinal enzyme, 2.1 mM, 50% inhibition
1,10-phenanthroline
-
-
1,10-phenanthroline
-
0.0024 mM, 50% inhibition, competitive vs. tryptophan
2,2'-dipyridyl
-
-
3,4-dihydroxyphenylalanine
-
-
3,4-Dihydroxyphenylethylamine
-
-
3,4-Dihydroxystyrene
-
-
3,4-methylenedioxymethamphetamine
-
inactivation of the enzyme
3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenylalanine
-
-
3-amino-3-[4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenyl]propanoic acid
-
-
3-[1-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)piperidin-4-yl]alanine
-
-
3-[3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-1H-pyrazol-1-yl]alanine
-
-
3-[5-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)pyridin-2-yl]alanine
-
-
4-(4-amino-6-[methyl[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-2-fluorophenylalanine
-
-
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-a-methylphenylalanine
-
-
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acid, which can selectively reduce serotonin levels in the intestine without affecting levels in the brain. It can selectively inhibit peripheral 5-HT synthesis without effects on the central nervous system because of very poor systemic exposure and the inability to cross the blood-brain barrier
4-(4-amino-6-[[(1S)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
4-(4-amino-6-[[(4'-methylbiphenyl-4-yl)methyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
4-(4-amino-6-[[4-(trifluoromethyl)benzyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
4-(5-[[(1-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
4-(5-[[(1-hydroxynaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
4-(5-[[(2'-methylbiphenyl-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
4-(5-[[(9-ethyl-9H-carbazol-3-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
4-(5-[[3-(cyclopentyloxy)-4-methoxybenzyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
4-chloro-L-phenylalanine
-
irreversible inhibitor
4-Chlorophenylalanine
-
i.e. PCPA, potent inhibitor of TPH
4-Chlorophenylalanine
-
-
4-ethynylphenylalanine
-
-
4-Fluorotryptophan
-
-
4-[4-(methylamino)-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-(1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-(2,2,2-trifluoro-1-[2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]ethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-(benzylamino)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-([[4'-(trifluoromethyl)biphenyl-4-yl]methyl]amino)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(1-biphenyl-4-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(1-methyl-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(1-tricyclo[3.3.1.1(3,7)]dec-1-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(2,2,2-trifluoro-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(2-methyl-1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(3,4-dimethylbenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(3-methyl-1-naphthalen-2-ylbutyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(4-phenoxybenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(biphenyl-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(biphenyl-3-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(biphenyl-4-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(cyclohexylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[2,2,2-trifluoro-1-(2-furan-2-ylphenyl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[2,2,2-trifluoro-1-(3'-methylbiphenyl-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-amino-6-[2,2,2-trifluoro-1-(5-furan-2-ylthiophen-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-morpholin-4-yl-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[4-[(1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
4-[5-[(3,4-dimethoxybenzyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
4-[5-[(4-cyanobenzyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
4-[5-[(biphenyl-4-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
4-[5-[(cyclohexylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
4-[5-[(furan-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
4-[5-[(pyridin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
4-[5-[(quinolin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
5-Fluorotryptophan
-
-
5-hydroxytryptophan
-
-
5-hydroxytryptophan
O96370
0.018 mM, 50% inhibition
6-Fluorotryptophan
-
1 mM, 90% inhibition of pineal tryptophan hydroxylase
6-Fluorotryptophan
-
-
8-hydroxyquinoline
-
-
Aroclor 1254
-
-
citalopram
P17752
selective serotonin reuptake inhibitors, like citalopram, exert their activity enhancing the general serotonergic tone, citalopram is the most selective one with little or no affinity for a variety of receptor types, association between gene TPH1 A218C polymorphism and citalopram antidepressant response in a Korean population, overview
Co2+
-
80% inhibition at 0.1 mM
CoCl2
-
1 mM, complete inhibition
D,L-4-chlorophenylalanine
-
-
D,L-4-chlorophenylalanine
O96370
0.009 mM, 50% inhibition
D-Dopa
-
noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
Desferrioxamine
-
0.010 mM or higher, irreversible loss of activity
dithiothreitol
-
-
dopamine
-
noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
dopamine
O96370
0.022 mM, 50% inhibition
dopamine
Q8IWU9
50% inhibition at 32 microM
Fe2+
-
-
H2O2
-
complete dependence on catalase in the absence of a mercaptan
L-4-chlorophenylalanine
-
-
L-5-hydroxytryptophan
-
-
L-Dopa
-
noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
L-erythro-7,8-dihydrobiopterin
-
recombinant N-terminal truncated enzyme, competitive vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
L-p-Chlorophenylalanine
-
-
L-phenylalanine
-
competitive vs. tryptophan
L-phenylalanine
-
substrate inhibition with tetrahydrobiopterin as cofactor, above 0.5 mM
L-phenylalanine
-
-
L-tryptophan
-
competitive to L-phenylalanine
L-tryptophan
-
substrate inhibition with 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine, not with 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, above 0.2 mM
L-tryptophan
-
substrate inhibition above 0.07 mM
L-tryptophan
-
TPH2, substrate inhibition
L-tryptophan
-
substrate inhibition above 0.1 mM
L-tryptophan
P70080
substrate inhibition at concentrations above 0.015 mM
L-tyrosine
-
noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
LP-533401
-
-
LP-615819
-
-
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
phenylalanine
-
-
serotonin
-
1 mM, 7.5% inhibition, 10 mM, 70% inhibition
tryptophan
-
substrate inhibition of the catalytic domain of TPH1
ZnSO4
-
1 mM, 80% inhibition
Mn2+
-
50% inhibition at 0.01 mM
additional information
-
no substrate inhibition by (6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
additional information
-
removal of 44 amino acids from the N-terminus of TPH2 results in a 3-4fold increased Vmax, which indicates a strong inhibitory function of this part on the enzymes activity
-
additional information
-
development and pharmacokinetic and pharmacodynamic effects of inhibitors inhibiting specifically the enzyme in the gastrointestinal tract, inhibitory potency on different genotypes, overview
-
additional information
-
development of antithrombotic miniribozymes that target peripheral tryptophan hydroxylase, overview
-
additional information
-
glucocorticoids inhibits TPH2 expression, the suppression is blocked by mifepristone, i.e. RU-486
-
additional information
Q8CGU9
glucocorticoids inhibits TPH2 expression, the suppression is blocked by mifepristone, i.e. RU-486
-
additional information
-
oxidation inhibits activity and leads to the formation of high molecular weight aggregates in a dithiothreitol-reversible manner, only cysteine-less mutants are resistant to this effect
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14-3-3 protein
-
activates the phosphorylated TPH2
-
2-mercaptoethanol
-
essential for activation
2-mercaptoethanol
-
30 mM, 79.3% activity compared to activation with dithiothreitol
2-mercaptoethylamine
-
30 mM, 93.8% activity compared to activation with dithiothreitol
2-mercaptopropionate
-
30 mM, 11.7% activity compared to activation with dithiothreitol
3-Mercaptopropionate
-
30 mM, 22% activity compared to activation with dithiothreitol
CaCl2
-
1 mM, 7% activation
dithiothreitol
-
-
dithiothreitol
-
or other sulfhydryl reagents like 2-mercaptoethanol and L-cysteine are essential for activation, 5fold increase in activity
dithiothreitol
-
10 mM
DTT
P70080
-
Fe(NH4)2(SO4)2
-
-
glutathione
-
30 mM, 16.1% activity compared to activation with dithiothreitol
L-cysteine
-
-
N-acetylcysteine
-
30 mM, 31.2% activity compared to activation with dithiothreitol
L-cysteine
-
30 mM, 79.5% activity compared to activation with dithiothreitol
additional information
-
enzyme expression and activity are increased in hypoxic rats, the effect is partially reversed by 4-chlorophenylalanine and is reduced in TPH1-deficient rats, overview
-
additional information
-
senescence-accelerated prone mouse 6 show increased serotonin levels, probably due to phosphorylation at Ser58, overview
-
additional information
-
phosphorylation at Ser19 by protein kinase A or Ca2+/calmodulin dependent protein kinase II activates TPH2 by about 30%, high-affinity binding of purified PKA-phosphorylated TPH2 bound to the 14-3-3 proteins gamma , epsilon and BMH1 causes further increased enzyme activity, 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
-
citalopram raises basal extracellular serotonin levels in DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele, but not in C57BL/6J and C57BL/6N mice carrying the 1473C allele, overview
-
additional information
-
phosphorylation of TPH2 at Ser19 within the regulatory domain of the enzyme by calmodulin-dependent protein kinase II activates the enzyme
-
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
-
additional information
Q8CGU9
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
-
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
-
pronase is most effective for activation. Trypsin, chymotrypsin, V8 protease and lysylendoprotease also activate PTMO, but the activity obtained using these proteases is only 5% of that with pronase
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.045
(6R)-5,6,7,8-tetrahydrobiopterin
-
substrate tryptophan
0.0128
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH2 fusion protein with maltose-binding protein
0.0202
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH2
0.0265
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
doubly truncated enzyme form DELTANH102-DELTACOOH402
0.027
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH1 fusion protein with maltose-binding protein
0.027
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH as fusion protein with maltose-binding protein expressed in Escherichia coli
0.039
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH1
0.039
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH expressed in Pichia pastoris
0.146
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH1, in vitro transcription and translation product
0.281
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH2, in vitro transcription and translation product
0.01789
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
0.0344
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
biphasic kinetic, low Km value
0.0684
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
Q8IWU9
-
0.796
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
biphasic kinetic, high Km value
2.1
(7R)-5,6,7,8-tetrahydrobiopterin
-
substrate tryptophan
0.006
2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine
-
soluble enzyme from brain
0.105
2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine
-
-
0.13
2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine
-
-
0.05
2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine
-
-
-
0.055
2-amino-4-hydroxy-6-methyltetrahydropteridine
-
substrate L-tryptophan
0.0752
2-amino-4-hydroxy-6-methyltetrahydropteridine
-
-
0.125
2-amino-4-hydroxy-6-methyltetrahydropteridine
-
tryptohan hydroxylase form I
0.125
2-amino-4-hydroxy-6-methyltetrahydropteridine
-
-
0.0865
2-azaisotryptophan
-
-
0.262
4-azatryptophan
-
-
0.994
4-methyltryptophan
-
-
0.295
6-azatryptophan
-
-
0.075
6-methyl-5,6,7,8-tetrahydrobiopterin
-
substrate tryptophan
0.053
6-methyl-tetrahydropterin
-
pH 7.0, 30C, recombinant isozyme TPH1
0.802
6-methyl-tetrahydropterin
-
pH 7.0, 30C, recombinant isozyme TPH2
0.0146
6-methyltetrahydropterin
-
recombinant N- and C-terminal truncated enzyme, substrate phenylalanine
0.177
6-methyltetrahydropterin
-
recombinant N- and C-terminal truncated enzyme, substrate tryptophan
0.0151
6-methyltryptophan
-
-
0.0662
7-azatryptophan
-
-
0.0375
7-methyltryptophan
-
-
0.022
L-phenylalanine
-
F313W mutant, recombinant N-terminal truncated enzyme
0.032
L-phenylalanine
-
enzyme from pineal gland, cofactor tetrahydrobiopterin
0.048
L-phenylalanine
-
recombinant N-terminal truncated enzyme
0.0606
L-phenylalanine
-
recombinant N- and C-terminal truncated enzyme, cofactor tetrahydrobiopterin
0.1
L-phenylalanine
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
0.102
L-phenylalanine
-
recombinant N- and C-terminal truncated enzyme, cofactor 6-methyltetrahydropterin
0.002
L-tryptophan
-
enzyme from crude mitochondrial fraction
0.0021
L-tryptophan
-
-
0.0058
L-tryptophan
-
recombinant N- and C-terminal truncated enzyme, cofactor 6-methyltetrahydrobipterin
0.0075
L-tryptophan
-
TPH as fusion protein with maltose-binding protein expressed in Escherichia coli
0.0075
L-tryptophan
P17532, Q8CGV2
TPH1, with 0.004 mM tetrahydrobiopterin; TPH1, with 0.004 mM tetrahydrobiopterin
0.0077
L-tryptophan
P70080
pH 7.0, 15C, recombinant TPH1
0.0078
L-tryptophan
-
doubly truncated enzyme form DELTANH102-DELTACOOH402
0.00873
L-tryptophan
-
-
0.0106
L-tryptophan
-
TPH1 fusion protein with maltose-binding protein
0.0131
L-tryptophan
-
TPH2, in vitro transcription and translation product
0.0132
L-tryptophan
-
0.02 mM ferrous ammonium, 0.5 mM (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, 30C
0.015
L-tryptophan
-
catalytic domain of TPH2
0.016
L-tryptophan
-
enzyme from pineal gland, cofactor tetrahydrobiopterin
0.0166
L-tryptophan
P17532, Q8CGV2
TPH1, with 0.4 mM tetrahydrobiopterin
0.017
L-tryptophan
-
F313W mutant, recombinant N-terminal truncated enzyme
0.0185
L-tryptophan
-
TPH expressed in Pichia pastoris
0.0186
L-tryptophan
Q8IWU9
pH 7.0, 30C, recombinant mutant R441H fusion enzyme
0.0192
L-tryptophan
P17532, Q8CGV2
TPH2, with 0.004-0.4 mM tetrahydrobiopterin
0.02
L-tryptophan
-
cofactor (6R)-5,6,7,8-tetrahydrobipterin
0.022
L-tryptophan
O96370
recombinant His-tagged enzyme
0.0228
L-tryptophan
-
TPH1
0.0228
L-tryptophan
-
catalytic domain of TPH1
0.023
L-tryptophan
-
-
0.023
L-tryptophan
-
cofactor 6-methyl-5,6,7,8-tetrahydrobipterin
0.02426
L-tryptophan
-
-
0.0255
L-tryptophan
Q8IWU9
pH 7.0, 30C, recombinant mutant P449R fusion enzyme
0.0282
L-tryptophan
Q8IWU9
pH 7.0, 30C, recombinant wild-type TPH2 fusion enzyme
0.031 - 0.033
L-tryptophan
-
activated enzyme in desalted extracts
0.032
L-tryptophan
-
cofactor tetrahydrobiopterin
0.033
L-tryptophan
-
recombinant N-terminal truncated enzyme
0.0334
L-tryptophan
Q8IWU9
pH 7.0, 30C, recombinant detagged mutant R441H
0.0403
L-tryptophan
-
TPH2
0.0413
L-tryptophan
Q8IWU9
; pH 7.0, 30C, recombinant detagged wild-type TPH2
0.0434
L-tryptophan
-
TPH2 fusion protein with maltose-binding protein
0.0449
L-tryptophan
-
pH 7.0, 30C, recombinant phosphorylated wild-type TPH2
0.045
L-tryptophan
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
0.0479
L-tryptophan
-
recombinant N- and C-terminal truncated enzyme, cofactor tetrahydrobiopterin
0.0511
L-tryptophan
Q8IWU9
pH 7.0, 30C, recombinant detagged mutant P449R
0.0545
L-tryptophan
-
pH 7.0, 30C, recombinant non-phosphorylated wild-type TPH2
0.0865
L-tryptophan
-
-
0.111
L-tryptophan
-
TPH1. in vitro transcription and translation product
0.119
L-tryptophan
-
tryptophan hydroxylase form I
0.119
L-tryptophan
-
-
0.3
L-tryptophan
-
soluble enzyme from brain
0.039
O2
P70080
pH 7.0, 15C, recombinant TPH1
0.109
O2
-
catalytic domain of TPH1
0.273
O2
-
catalytic domain of TPH2
0.09
phenylalanine
-
cofactor (6R)-5,6,7,8-tetrahydrobipterin
0.286
phenylalanine
-
cofactor tetrahydrobiopterin
0.0067
tetrahydrobiopterin
O96370
recombinant His-tagged enzyme
0.0142
tetrahydrobiopterin
-
recombinant N- and C-terminal truncated enzyme, substrate phenylalanine
0.0147
tetrahydrobiopterin
Q8IWU9
pH 7.0, 30C, recombinant mutant P449R fusion enzyme
0.015
tetrahydrobiopterin
-
pH 7.0, 30C, recombinant isozyme TPH1
0.0217
tetrahydrobiopterin
Q8IWU9
pH 7.0, 30C, recombinant wild-type TPH2 fusion enzyme
0.0249
tetrahydrobiopterin
Q8IWU9
pH 7.0, 30C, recombinant mutant R441H fusion enzyme
0.0265
tetrahydrobiopterin
-
catalytic domain of TPH2
0.0289
tetrahydrobiopterin
Q8IWU9
pH 7.0, 30C, recombinant detagged mutant R441H
0.031
tetrahydrobiopterin
-
-
0.0351
tetrahydrobiopterin
-
pH 7.0, 30C, recombinant non-phosphorylated wild-type TPH2
0.0423
tetrahydrobiopterin
-
pH 7.0, 30C, recombinant phosphorylated wild-type TPH2
0.0518
tetrahydrobiopterin
Q8IWU9
pH 7.0, 30C, recombinant detagged mutant P449R
0.0684
tetrahydrobiopterin
Q8IWU9
pH 7.0, 30C, recombinant detagged wild-type TPH2
0.077
tetrahydrobiopterin
-
pH 7.0, 30C, recombinant isozyme TPH2
0.135
tetrahydrobiopterin
-
recombinant N- and C-terminal truncated enzyme, substrate tryptophan
0.294
tetrahydrobiopterin
-
activated enzyme in desalted extracts
0.315
tetrahydrobiopterin
-
catalytic domain of TPH1
0.324
tetrahydrobiopterin
P70080
pH 7.0, 15C, recombinant TPH1
0.05
tryptophan
-
cofactor tetrahydrobiopterine
0.078
tryptophan
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
0.29
tryptophan
-
cofactor 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine
0.355
L-tryptophan
-
-
additional information
additional information
-
1.2% O2 with 0.2 mM 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine, 7.1% O2 with 0.4 mM 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine
-
additional information
additional information
-
20% O2, cofactor 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, 2.5% O2, cofactor tetrahydrobipterine
-
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
-
additional information
additional information
Q8IWU9
isozymes TPH1 and TPH2 kinetics, overview
-
additional information
additional information
-
kinetics of phosphorylated and non-phosphorylated wild-type and mutant enzymes
-
additional information
additional information
-
kinetics of wild-type isozyme TPH1, overview; kinetics of wild-type isozyme TPH2 and of TPH2 deletion mutants, overview
-
additional information
additional information
P17752, Q8IWU9
kinetic mechanism of isozyme TPH1; kinetic mechanism of isozyme TPH2
-
additional information
additional information
P17532, Q8CGV2
kinetic mechanism of isozyme TPH1; kinetic mechanism of isozyme TPH2
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.217
2-azaisotryptophan
-
-
0.358
4-azatryptophan
-
-
0.273
4-methyltryptophan
-
-
0.533
6-azatryptophan
-
-
0.0733
6-methyltryptophan
-
-
0.252
7-azatryptophan
-
-
0.315
7-methyltryptophan
-
-
0.207
L-tryptophan
-
-
2.67
L-tryptophan
-
catalytic domain of TPH1
5.03
L-tryptophan
-
catalytic domain of TPH2
32
L-tryptophan
P70080
pH 7.0, 15C, recombinant TPH1
1.383
O2
-
catalytic domain of TPH1
6.73
O2
-
catalytic domain of TPH2
22.8
O2
P70080
pH 7.0, 15C, recombinant TPH1
2.167
tetrahydrobiopterin
-
catalytic domain of TPH1
4.567
tetrahydrobiopterin
-
catalytic domain of TPH2
43
tetrahydrobiopterin
P70080
pH 7.0, 15C, recombinant TPH1
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00082
1,10-phenanthroline
-
vs. tryptophan
0.0026
1,10-phenanthroline
-
vs. 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine
0.021
D,L-4-chlorophenylalanine
-
-
0.0761
D-Dopa
-
vs. L-tryptophan
0.202
D-Dopa
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with low affinity
0.609
D-Dopa
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with high affinity
0.007
dopamine
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with high affinity
0.0393
dopamine
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with low affinity
0.0943
dopamine
-
vs. L-tryptophan
0.026
L-4-chlorophenylalanine
-
-
0.035
L-5-hydroxytryptophan
-
-
0.017
L-Dopa
-
vs. L-tryptophan
0.0803
L-Dopa
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with high affinity
0.0887
L-Dopa
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with low affinity
0.161
L-erythro-7,8-dihydrobiopterin
-
recombinant truncated enzyme
0.0727
L-phenylalanine
-
0.02 mM ferrous ammonium, 0.5 mM (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, 30C
0.197
L-phenylalanine
-
-
0.072
L-tryptophan
-
catalytic domain of TPH1
0.164
L-tryptophan
P70080
pH 7.0, 15C, recombinant TPH1
0.0162
L-tyrosine
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with high affinity
0.0185
L-tyrosine
-
vs. L-tryptophan
0.306
L-tyrosine
-
vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, component with low affinity
0.15
phenylalanine
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.011
3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenylalanine
-
-
0.00377
3-amino-3-[4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenyl]propanoic acid
-
-
0.00077
3-[1-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)piperidin-4-yl]alanine
-
-
0.0126
3-[3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-1H-pyrazol-1-yl]alanine
-
-
0.00089
3-[5-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)pyridin-2-yl]alanine
-
-
0.00005
4-(4-amino-6-[methyl[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.0002
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-2-fluorophenylalanine
-
-
0.0111
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-a-methylphenylalanine
-
-
0.000026
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.000026
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.000032
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.000044
4-(4-amino-6-[[(1S)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.000014
4-(4-amino-6-[[(4'-methylbiphenyl-4-yl)methyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.00012
4-(4-amino-6-[[4-(trifluoromethyl)benzyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
-
0.000046
4-(5-[[(1-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
0.000013
4-(5-[[(1-hydroxynaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
0.00004
4-(5-[[(2'-methylbiphenyl-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
0.000031
4-(5-[[(9-ethyl-9H-carbazol-3-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
0.000045
4-(5-[[3-(cyclopentyloxy)-4-methoxybenzyl]amino]pyrazin-2-yl)-L-phenylalanine
-
-
0.092
4-Chlorophenylalanine
-
-
0.03
4-ethynylphenylalanine
-
-
0.00061
4-[4-(methylamino)-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00038
4-[4-amino-6-(1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00018
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00032
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000029
4-[4-amino-6-(2,2,2-trifluoro-1-[2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]ethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.0005
4-[4-amino-6-(benzylamino)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00016
4-[4-amino-6-([[4'-(trifluoromethyl)biphenyl-4-yl]methyl]amino)-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000024
4-[4-amino-6-[(1-biphenyl-4-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000055
4-[4-amino-6-[(1-methyl-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00015
4-[4-amino-6-[(1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000019
4-[4-amino-6-[(1-tricyclo[3.3.1.1(3,7)]dec-1-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00033
4-[4-amino-6-[(2,2,2-trifluoro-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00025
4-[4-amino-6-[(2-methyl-1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.0001
4-[4-amino-6-[(3,4-dimethylbenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00012
4-[4-amino-6-[(3-methyl-1-naphthalen-2-ylbutyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00015
4-[4-amino-6-[(4-phenoxybenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000007
4-[4-amino-6-[(biphenyl-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000038
4-[4-amino-6-[(biphenyl-3-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00006
4-[4-amino-6-[(biphenyl-4-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00012
4-[4-amino-6-[(cyclohexylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000024
4-[4-amino-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000024
4-[4-amino-6-[2,2,2-trifluoro-1-(2-furan-2-ylphenyl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00007
4-[4-amino-6-[2,2,2-trifluoro-1-(3'-methylbiphenyl-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000054
4-[4-amino-6-[2,2,2-trifluoro-1-(5-furan-2-ylthiophen-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00156
4-[4-morpholin-4-yl-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.00019
4-[4-[(1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
-
0.000069
4-[5-[(3,4-dimethoxybenzyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
0.00011
4-[5-[(4-cyanobenzyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
0.000044
4-[5-[(biphenyl-4-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
0.00024
4-[5-[(cyclohexylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
0.00096
4-[5-[(furan-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
0.00615
4-[5-[(pyridin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
0.00019
4-[5-[(quinolin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000018
-
enzyme from carconoid tumor
0.000064
Q8IWU9
recombinant mutant R441H TPH2 in HEK-293 cells
0.00018
-
partially purified enzyme from hindbrain
0.00052
Q8IWU9
recombinant wild-type TPH2 in HEK-293 cells
0.00165
Q8IWU9
recombinant mutant P449R TPH2 in HEK-293 cells
0.0021
-
hindbrain enzyme
0.0144
-
purified recombinant enzyme, pH and temperature not specified in the publication
0.0214
-
TPH expressed in Pichia pastoris
0.0271
-
brain tryptophan hydroxylase
0.045
-
brain tryptophan hydroxylase
0.082
-
tryptophan hydroxylase form II
0.17
O96370
recombinant His-tagged enzyme
0.235
-
tryptophan hydroxylase from pineal gland
0.296
-
TPH as fusion protein with maltose-binding protein expressed in Escherichia coli
0.367
-
brain tryptophan hydroxylase
0.374
-
brain stem, tryptophan hydroxylase form I
0.434
-
recombinant enzyme, activity in cell extracts
0.6
-
recombinant pineal enzyme
0.6
P70080
purified recombinant TPH1
5.28
-
purified from mastocytoma cells
5.28
-
-
13.3
-
liver enzyme
additional information
-
enzyme activity decreases in 4-, 8-, and 12-week-old mice expressing exon 1 of human huntingtin gene by 62, 61 and 86% respectively compared to control animals
additional information
-
5-HT synthesis rates and tissue contents in normoxic mice harboring the C1473G polymorphism of the Tph2 gene, overview
additional information
-
-
additional information
-
determination of extracellular 4-hydroxytryptamine
additional information
Q8CGV2
activities of genetic variants of TPH2 in strains C57BL/6 and CC57BR, and in F2 hybrids of these strains, the C7C genotype shows 2fold higher activity compared to the G/G genotype of the C1473G polymorphism, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4
-
in the presence of 0.2 mM Fe2+ and 2-mercaptoethanol
6.8
-
in the presence of 0.2 mM Fe2+, without 2-mercaptoethanol
7
Q8IWU9
assay at
7
-
assay at
7
-
assay at
7
P70080
assay at
7.2
-
in the presence of 35.5 mM 2-mercaptoethanol
7.4
-
assay at
7.5
-
assay at
7.5
-
assay at
7.6
-
tryptophan hydroxylase form I
7.6
-
without 2-mercaptoethanol and Fe2+
8 - 8.5
-
soluble enzyme from brain
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.7
-
about 50% activity at pH 6.0 and 8.7
6 - 9.5
-
about 50% activity at pH 6 and 9.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15
P70080
assay at
30
Q8IWU9
assay at
30
-
assay at
30
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Q8IWU9
expression of the native truncated mutant TPH2
Manually annotated by BRENDA team
-
activity in hypothalamus and midbrain-medulla regions, no activity in cerebellum or cortex
Manually annotated by BRENDA team
-
serotonergic neurons
Manually annotated by BRENDA team
-
region of the raphe nucleus of rat midbrain
Manually annotated by BRENDA team
Q8CGV2
TPH2
Manually annotated by BRENDA team
-
TPH2, exclusively in brain
Manually annotated by BRENDA team
-
the selective serotonin reuptake inhibitor citalopram has no effect in mice strain that exhibit a reduced 5-hydroxy-L-tryptophan synthesis due to a mutatation in the tryptophan hydroxylase 2
Manually annotated by BRENDA team
-
circadian expression of TPH in dorsal and median raphe in correlation to glucocorticoid fluctuations, e.g. corticosterone, expression pattern, overview
Manually annotated by BRENDA team
-
dorsal and median raphe
Manually annotated by BRENDA team
-
dorsal and median raphe nuclei, in the dorsal raphe nucleus there are more serotonin neurons and more neuronal TPH2 expression postmortem in depressed suicides. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls
Manually annotated by BRENDA team
-
dorsal raphe nuclei
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Q8CGU9
expression analysis of TPH2
Manually annotated by BRENDA team
-
expression of TPH2
Manually annotated by BRENDA team
-
immunohistochemic analysis for TPH-like reactivity, neuronal distribution, overview
Manually annotated by BRENDA team
-
in raphe nuclei, in lateral hypothalamic nuclei and in pineal body
Manually annotated by BRENDA team
Q8CGU9
in raphe nuclei, in lateral hypothalamic nuclei and in pineal body
Manually annotated by BRENDA team
P17752, Q8IWU9
mainly TPH2
Manually annotated by BRENDA team
-
prefrontal cortex and dorsal hippocampus
Manually annotated by BRENDA team
Q8CGU9
raphe nuclei
Manually annotated by BRENDA team
Q8IWU9
specific expression of isozyme TPH2
Manually annotated by BRENDA team
P17532, Q8CGV2
temporal expression pattern of TPH1
Manually annotated by BRENDA team
P17532, Q8CGV2
temporal expression pattern of TPH2
Manually annotated by BRENDA team
P17752, Q8IWU9
TPH1 is expressed predominantly during the late developmental stage in the brain
Manually annotated by BRENDA team
B3VBU9, B3VBV0
high expression of TPH-1 throughout the brain but is greatest in the hypothalamic region
Manually annotated by BRENDA team
B3VBU9, B3VBV0
high expression of TPH-2 throughout the brain but it is greatest in the hypothalamic region
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
in raphe nuclei, in lateral hypothalamic nuclei and in pineal body
-
Manually annotated by BRENDA team
-
expression analysis
Manually annotated by BRENDA team
Q8IWU9
expression of the native truncated mutant TPH2
Manually annotated by BRENDA team
Q8CGU9
TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus and in the brainstem containing the rest of the raphe complex
Manually annotated by BRENDA team
B3VBU9, B3VBV0
high expression of TPH-1
Manually annotated by BRENDA team
B3VBU9, B3VBV0
high expression of TPH-2
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
pituitary cell line
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-1
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-2
Manually annotated by BRENDA team
P17752, Q8IWU9
TPH2
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-2
Manually annotated by BRENDA team
Q8IWU9
expression of the native truncated mutant TPH2
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-2
Manually annotated by BRENDA team
A1Y9J6
TPH expression pattern during development, TPH expression was found from tailbud stage in the precursor cells of the visceral ganglion and in the tail
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-2
Manually annotated by BRENDA team
-
in vivo predominantly localized to normal and malignant melanocytes
Manually annotated by BRENDA team
A7VKD9
main expression of gene TPH at commissure axonal connections in the ventral nerve cords
Manually annotated by BRENDA team
-
expressed predominantly in serotonergic neurons
Manually annotated by BRENDA team
Q8IWU9
neural isozyme TPH2
Manually annotated by BRENDA team
Q8CGU9
primary serotonergic, from raphe nuclei
Manually annotated by BRENDA team
-
serotonergic
Manually annotated by BRENDA team
A7VKD9
serotonergic
Manually annotated by BRENDA team
-
serotonergic, expression of TPH2
Manually annotated by BRENDA team
-
TPH2, serotonergic neurons
Manually annotated by BRENDA team
A1Y9J6
TPHexpressing neurons form two clusters in the anterior central nervous system at the level of the visceral ganglion
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-1
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-2
Manually annotated by BRENDA team
-
expression of TPH2
Manually annotated by BRENDA team
Q8IWU9
expression of the native truncated mutant TPH2
Manually annotated by BRENDA team
-
human small cell lung carcinoma cell line, SHP-77 cells preferentially express TPH1 over TPH2 mRNA
Manually annotated by BRENDA team
-
ventral horn, enzyme expression in muscle after exercise-induced fatigue and control muscle, overview
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-1
Manually annotated by BRENDA team
B3VBU9, B3VBV0
low levels of TPH-2
Manually annotated by BRENDA team
Q8CGU9
TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus and in the brainstem containing the rest of the raphe complex
Manually annotated by BRENDA team
additional information
-
analysis of TPH2 expression in brain tissues, overview
Manually annotated by BRENDA team
additional information
Q8CGU9
analysis of TPH2 expression in brain tissues, overview
Manually annotated by BRENDA team
additional information
-
enzyme distribution between optic lobe and protocerebrum, dorsal protocerebrum, deutocerebrum, and subesophageal ganglion, overview
Manually annotated by BRENDA team
additional information
A7VKD9
expression pattern of TPH in whole animals, in situ hybridization, overview
Manually annotated by BRENDA team
additional information
-
expression pattern of tryptophan hydroxylase in senescence-accelerated prone mouse 6, overview
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
additional information
-
tissue distribution and expression levels of TPH2 and TPH1 in normoxic and hypoxic wild-type and mutant mice, overview
Manually annotated by BRENDA team
additional information
-
TPH1 is found in the periphery and pineal gland whereas TPH2 is expressed specifically in the central nervous system
Manually annotated by BRENDA team
additional information
-
TPH1 is primarily expressed in the pineal gland and non-neuronal tissues, such as enterochromaffin cells of the gastrointestinal tract. TPH2, the dominant isozyme in the brain, is expressed exclusively in neuronal cells, such as dorsal raphe or myenteric plexus cells
Manually annotated by BRENDA team
additional information
P17752, Q8IWU9
TPH1 mRNA is mainly expressed in the pineal gland and the periphery
Manually annotated by BRENDA team
additional information
P17752, Q8IWU9
TPH2 mRNA is preferentially expressed in the brain and in the peripheral myenteric neurons in the gut
Manually annotated by BRENDA team
additional information
-
dorsal raphe
Manually annotated by BRENDA team
additional information
B3VBU9, B3VBV0
TPH-1 is absent from heart, intestine kidney, muscle, and liver
Manually annotated by BRENDA team
additional information
B3VBU9, B3VBV0
TPH-2 is absent from intestine and muscle
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6
-
analysis of TPH2 expression in brain tissues, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
-
enzyme from pineal gland, gel filtration, sucrose density gradient ultracentrifugation
438660
36100
-
catalytic domain of TPH1, gel filtration
706609
36200
-
catalytic domain of TPH2, gel filtration
706609
55000
B3VBU9, B3VBV0
sequence analysis
705929
56000
B3VBU9, B3VBV0
sequence analysis
705929
59000
-
SDS-PAGE
671723
97000
-
SDS-PAGE, maltose-binding protein fusion protein
676182
162000
-
gel filtration
704354
200000
-
recombinant pineal enzyme, gel filtration
438675
220000 - 240000
-
enzyme from hindbrain
438654
230000
-
gel filtration, PAGE, sucrose density gradient centrifugation
438668
234000
-
TPH1, gel filtration
659761
236000
-
gel filtration
671723
240000
O96370
recombinant His-tagged enzyme, gel filtration
438673
240300
Q8IWU9
gel-filtration
675511
260000
-
enzyme from brain, gradient PAGE
438663
270000
-
enzyme from mastocytoma cells, gel filtration
438658, 438661
274000
-
TPH2, gel filtration
659761
280000
-
enzyme from mastocytoma cells, gradient PAGE
438658, 438661
280000
-
liver enzyme, gel filtration
438671
288000
-
-
438654
288000
-
tryptophan hydroxylase form I, gradient PAGE
438656
288000
-
-
438662
300000
-
-
438654
300000
-
tryptophan hydroxylase form I, gel filtration
438656
300000
-
-
438662
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 90000, SDS-PAGE
?
-
x * 55000, brain enzyme, SDS-PAGE
?
-
x * 47000, recombinant enzyme, SDS-PAGE
?
Q2HZ26
x * 50000, about, recombinant enzyme, SDS-PAGE
?
Mus musculus C57BL/6
-
x * 47000, recombinant enzyme, SDS-PAGE
-
homotetramer
-
4 * 56000, SDS-PAGE
tetramer
-
-
tetramer
-
-
tetramer
-
2 * 57700 + 2 * 60900, hindbrain enzyme, SDS-PAGE
tetramer
-
2 * 57500 + 2 * 60000, midbrain enzyme, SDS-PAGE
tetramer
-
4 * 59000, tryptophan hydroxylase form I from brain stem, SDS-PAGE
tetramer
O96370
4 * 60000, His-tagged recombinant enzyme, immunoblot
tetramer
-
4 * 96000, SDS-PAGE
tetramer
-
4 * 50000, recombinant pineal enzyme, SDS-PAGE
tetramer
-
4 * 53000, enzyme from mastocytoma cells, SDS-PAGE
tetramer
-
4 * 58500, TPH1, 4 * 68500, TPH2
tetramer
-
4 * 59000, gel filtration and SDS-PAGE
tetramer
A7VKD9
a conserved leucine zipper in the C-terminal domain is required for the tetramerization of TPH, overview
tetramer
Q8IWU9
structure molecular modelling of TPH2 wild-type and mutants
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
TPH1 is phosphorylated by cAMP-dependent protein kinase A, TPH2 is phosphorylated by cAMP-dependent protein kinase A
phosphoprotein
-
phosphorylation of TPH2 at Ser19 by calmodulin-dependent protein kinase II activates the enzyme
phosphoprotein
-
TPH2 is phosphorylated by protein kinase A at Ser19 and Ser104, and by Ca2+/calmodulin dependent protein kinase II at Ser19, phosphorylation at Ser19 activates TPH2 by about 30%, Ser19 is phosphorylated to a stoichiometry of up to 50% in HEK-293 cells expressing TPH2, overview, in vivo phosphorylation in transiently transfected HEK-293 cells occurs with Ser19 phosphorylation stoichiometry of maximally 0.5 mol of phosphate/mol of enzyme subunit in resting cells, which is increasable by cell activation with okadaic acid, overview
phosphoprotein
-
tryptophan hydroxylase becomes phosphorylated at Ser58 in brain stem of 1-month-old SAMP6
additional information
-
less than 1% bound carbohydrate
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
catalytic domain (DETLA1-100/DELTA415-445) of TPH1 in complex with the tryptophan substrate and an iron-bound imidazole, by vapor diffusion method with sitting drops, at 1.9 A resolution, crystallization time of 3-6 months. Loops of residues Leu124-Asp139 and Ile367-Thr369 close around the active site. The tryptophan substrate is bound close to the iron in a binding pocket distinct from the BH4 binding pocket. The hydrophobic part of the tryptophan binding pocket is lined by residues Tyr236, Thr266, Pro269, His273, Phe314, Phe319, and Ile367, while the polar interactions of the tryptophan are with Thr266, Ile367, and Ser337 and a salt bridge to Arg258. The overall structure is more compact with two loops closing around the active site, when compared to the structure of human catalytic domain of TPH1
P70080
purified enzyme without 7,8-dihydro-L-biopterin, sitting drop vapour diffusion method, 0.002 ml of 4.2 mg/ml protein in 20 mM Tris/NaOH, 100 mM (NH4)2SO4 pH 8.5, is mixed with 0.002 ml of reservoir solution containing 0.2 M imidazole malate, pH 8.5, 22.5% PEG 10000, and tetrahydrobiopterin in excess, X-ray diffraction structure determination and analysis at 3.0 A reslution
P70080
compound 4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine co-crystallized with TPH1
-
modeled structure based on the known crystal structures of phenylalanine hydroxylase and tyrosine hydroxylase
-
sitting drop vapor diffusion method, X-ray crystal structure of a truncated functional form of enzyme (DELTANH102-DELTACOOH402) with the bound cofactor analogue 7,8-dihydro-L-biopterin
-
residue Phe241 forms a displaced sandwich-type pi-complex with tetrahydrobiopterin, this complex has a counterpoise-corrected second order Moller Plesset Theory interaction energy of about 24.68 kcal/mol
synthetic construct
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 10
-
enzyme retains more than 80% activity after 60 min at 4C between pH 7.0 and pH 7.6, unstable above pH 10.0 and below pH 5.0
438671
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
complete loss of activity in absence of stabilizing agents after 20 h
438658
4
-
complete loss of activity in absence of stabilizing agents after 24 h
438659
4
-
complete loss of activity in absence of stabilizing agents after 20 h
438661
35
-
stable below
438671
37
-
half-life: 54 min
438673
37
O96370
80 min, no loss of activity, estimated half-life: 21 h
438673
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one strongly stabilizes the protein during denaturation by heat. Half-denaturation temperature increases from 55.5C to 64.4C in the presence of 0.1 mM 3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one.
-
high-affinity binding of purified PKA-phosphorylated TPH2 bound to the 14-3-3 proteins gamma , epsilon and BMH1 causes increased enzyme stability
-
The half-life of the protein is 30 min at 37C, while the N-terminal and the N- and C-terminal truncated mutants exhibit half-lives of 203 min and 147 min, respectively
-
tryptophan and glycerol stabilize
-
catalase at a concentration of more than 1 mg/ml is required for stability during reaction at aerobic conditiones
-
EDTA stabilizes
-
EDTA: 0.05 mM stabilizes
-
ethylene glycol, 50%, stabilizes
-
NaCl: 1 M, in addition to other stabilizing agents brings a great improvement in stabilization
-
Tween 20 stabilizes
-
Tween 20: 0.06% stabilizes
-
EDTA stabilizes
-
Fe2+ protects against inactivation by H2O2 in absence of catalase
-
glycerol stabilizes
-
Tween 20 stabilizes
-
catalase is necessary to protect the enzyme during purification
-
EDTA: 0.05 mM stabilizes
-
glycerol, 10% stabilizes
-
L-tryptophan stabilizes
-
Tween 20: 0.06% stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 2 months, 40% loss of activity
-
4C, under N2, 2 months, no loss of activity
-
4C, under O2, 48 h, 90% loss of activity
-
-20C, 10% glycerol, 0.05 mM EDTA, 0.06% Tween 20, 28 d, 69% loss of activity
-
-80C, 1 month, 30% loss of activity
-
4C, 0.06% Tween 20, 0.05 mM EDTA, 50% ethylene glycol, 1 M NaCl, 5 days, no loss of activity
-
4C, 10% glycerol, 0.05 mM EDTA, 0.06% Tween 20, 28 d, 34% loss of activity
-
-80C, N2 atmosphere, dithiothreitol, 2 weeks, 20% loss of activity
-
N- and C-terminal truncated recombinant enzyme, -70C, 100 mM ammonium sulfate, ferrous iron, 10% glycerol, 2 mM dithiothreitiol, pH 7.0, indefinitely, no loss of activity
-
-80C, 1 month, 20% loss of activity
-
0C, 20 h, 60% loss of activity
-
recombinant His-tagged enzyme, -80C, 50 mM HEPES, pH 7.5, 200 mM NaCl, 10% glycerol, 0.05% Tween 20, 1 mM dithiothreitol, 4 days, no loss of activity
O96370
recombinant His-tagged enzyme, 4C, 50 mM HEPES, pH 7.5, 200 mM NaCl, 10% glycerol, 0.05% Tween 20, 1 mM dithiothreitol, 4 days, no loss of activity
O96370
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme from pineal gland, ammonium sulfate, hydroxylapatite, P-cellulose, DEAE-cellulose, Sephadex G-200
-
glutathione-Sepharose column chromatography, and gel filtration
-
catalytic domain (DETLA1-100/DELTA415-445) of TPH1
P70080
recombinant catalytic domain of chicken TPH isoform 1 from Escherichia coli strain BL21(DE3) by anion exchange chromatography and gel filtration to homogeneity, release from the fusion by in vivo cleavage by a co-expressed ubiquitin-specific, carboxy-terminal protease
P70080
by a rapid batch method
-
by gel filtration and ultrafiltration; by gel filtration and ultrafiltration
-
Ni-affinity chromatography
-
purified by amylose resin affinity chromatography
-
recombinant enzyme
-
recombinant full-length and N-terminal truncated enzyme
-
recombinant GST-tagged TPH2 from Escherichia coli by glutathione affinity chromatography
-
recombinant His-tagged wild-type and mutant TPH2s from Escherichia coli
-
recombinant His6-MBP-fusion TPH2 wild-type and mutants from Escherichia coli by affinity chromatography, fusion protein cleavage, and gel filtration; two chromatography steps
Q8IWU9
recombinant pineal enzyme, ammonium sulfate, Pterin-agarose, Sepharose
-
2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine-agarose
-
one chromatography step, 98% homogeneity
-
purified and cleaved from its fusion tag
-
recombinant isozymes TPH1 and TPH2 from Escherichia coli by pterin affinity chromatography
-
brain enzyme, calcium phosphate gel, dimethyltetrahydropteridine-agarose
-
hindbrain enzyme, calcium phosphate gel, polyethylene glycol 6000, Sepharose 6B, DEAE-cellulose
-
recombinant N- and C-terminal truncated mutant enzyme
-
brain enzyme, calcium phosphate gel, dimethyltetrahydropteridine-agarose
-
tryptophan hydroxylase form I and II, pH 4.8, ammonium sulfate, gel filtration, DEAE-Sepharose, 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine-agarose
-
recombinant His-tagged enzyme, Nickel affinity chromatography
O96370
acid treatment, ammonium sulfate, Sepharose CL-6B, DEAE-sepharose, butyl-Sepharose, Toyopearl
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene tph, DNA and amino acid sequence deterination and analysis, expression analysis, phylogenetic analysis
A1Y9J6
expressed in Escherichia coli
-
gene TPH, DNA and amino acid sequence determination and analysis
A7VKD9
catalytic domain (DETLA1-100/DELTA415-445) of TPH1, expression in Escherichia coli
P70080
high yield expression of the catalytic domain of chicken TPH isoform 1, comprising residues 1-100 and 415-445, fused to ubiquitin in Escherichia coli strain BL21(DE3)
P70080
a His-tagged version and a maltose binding protein-fusion protein are expressed in Escherichia coli
-
catalytic domain of TPH1 (DELTA1-99 TPH1 DELTA414-444) amplified, the cTPH/NdeI/XhoI gene cloned into the pET26 vector, expressed in Escherichia coli BL21(DE3) cells; catalytic domain of TPH2 (DELTA1-145 TPH2 DELTA460-490) amplified, the cTPH/NdeI/XhoI gene cloned into the pET26 vector, expressed in Escherichia coli BL21(DE3) cells
-
DNA and amio acid sequence determination and analysis of short and long isozymes TPH2, expression analysis in brain
Q8IWU9
expression analysis of wild-type and mutant enzymes in brain samples
-
expression as maltose-binding protein fusion protein in Escherichia coli BL21 (DE3)
-
expression as maltose-binding protein fusion protein in Escherichia coli; gene tph2, expression of TPH2 wild-type and mutants in Escherichia coli and in HEK-293 cells
Q8IWU9
expression in Escherichia coli
-
expression in escherichia coli and Pichia pastoris, His-Patch-thioredoxin-TPH, 6His-TPH or as a fusion protein with maltose-binding protein
-
expression in Escherichia coli BL21-CodonPlus(DE3)-RIL as His-tag fusion protein
-
expression in HeLa cells
-
expression in RN46A cells, transcriptional activity of the rat TPH2 promoter, overview
-
expression of full-length and N-terminal truncated enzyme in Escherichia coli
-
expression of GST-tagged TPH2 in Escherichia coli
-
expression of wild-type and mutant isozymes TPH2 in Escherichia coli as His-tagged enzyme, and of wild-type TPH2 in HEK-293 cells
-
expression of wild-type isozyme TPH1 in COS7 cells; expression of wild-type isozyme TPH2, and of TPH2 deletion mutants in COS7 cells
-
gene TPH1 genotyping of female and male Caucasian patients with major depression
P17752
gene TPH1, DNA and amino acid sequence determination and analysis, genotyping in Han Chinese subjects; gene TPH2, DNA and amino acid sequence determination and analysis, genotyping in Han Chinese subjects
P17752, Q8IWU9
gene TPH1, genotyping in Japanese population of healthy persons and shizophrenia patients
-
gene TPH2 is located on chromosome 12q15 comprising 11 exons, DNA and amino acid determination and analysis, genotyping of a population of alcohol-dependent patients of Caucasian origin from southern Germany
Q8IWU9
gene TPH2 located on the long arm of chromosome 12 at 12q21.1, DNA and amino acid sequence determination and analysis, genotyping
Q8IWU9
gene TPH2, DNA and amino acid sequence determination and analysis of wild-type and mutant genes, genotyping, overview
-
gene TPH2, DNA and amino acid sequence determination and analysis, genotyping
P17752, Q8IWU9
gene TPH2, DNA and amino acid sequence determination and analysis, genotyping, overview
Q8IWU9
gene TPH2, DNA and amino acid sequence determination, identification of 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, permutations of the motif reveal considerable flexibility in the juxtaposition of the two halves of bipartite NRSE, expressionin rat C6-glioma cells, quantitative reverse transcription-PCR expression analysis, sequence comparisons
-
genes TPH1 and TPH2, expression analysis, overview, expression of wild-type TPH1 and TPH2 in rat PC-12 cells, in vitro transcription and translation using reticulocyte lysate, the TPH2 extended N-terminal domain plays a role in modulating the enzyme expression, expression of mutant HA-TPH2-(1-41)-TPH1 in HEK-293 amd PC-12 cells, the expression level of the chimeric protein is significantly decreased compared with TPH1 in both cell lines and is more similar to that of TPH2, the N-terminal regulatory determinant is transferable, overview
-
genotyping of borderline personality disorder patients and healthy persons
-
isozyme TPH1, DNA and amino acid sequence determination and analysis, TPH1 is located on chromosome 11, expression analysis; isozyme TPH2, DNA and amino acid sequence determination and analysis, TPH2 is on chromosome 12, expression analysis
P17752, Q8IWU9
TPH1 and TPH2 genotyping
-
TPH1, expression in Escherichia coli; TPH2, expression in Escherichia coli
-
TPH1, genotyping in Korean population with major depressive disorder patients, overview
P17752
TPH2, DNA and amino acid sequence determination and analysis, genotyping
-
wild-type and missense mutants from vector pETM41 for 6 x His-MBP-TPH2 expression in Escherichia coli BL21-Codon Plus (DE3)-RIPL cells, and vector pcDNA5/FRT, for expression in a cell free expression system and in HEK-293 cells. Rabbit reticulocyte lysate used to express TPH2 wild-type and missense variants
-
gene TPH2, cloning of four haplotypes of TPH2 into pcDNA3.1 and stable transfected into rat PC-12 cells, transient expressionin HEK-293 cells, quantitative real-time PCR expression analysis and comparison of mRNA stabilities, overview
Q2HZ26
PCR products ligated and cloned into pGEM-T easy vector; PCR products ligated and cloned into pGEM-T easy vector
B3VBU9, B3VBV0
expression in Escherichia coli
-
expression of isozymes TPH1 and TPH2 in Escherichia coli
-
expression of TPH2 in COS cells
-
genes Tph1 and Tph2, expression analysis in wild-type and mutant mice, overview
-
glutathione S-transferase-fusion protein expressed in Escherichia coli, expressed in HEK293-cell, eGFP-fusion protein expressed in HEK293-cell
-
into pT vector and linearized with Nco I prior to antisense transcription with SP6
-
isozyme TPH1, DNA and amino acid sequence determination and analysis, tissue-specific and developmental expression analysis, expression of His6-tagged TPH1 in COS7 cells; isozyme TPH2, DNA and amino acid sequence determination and analysis, tissue-specific and developmental expression analysis, expression of His6-tagged TPH2 in COS7 cells
P17532, Q8CGV2
secondary structure of TPH1 RNA, overview
-
expression of wild-type and N- and C-terminal truncated mutant enzyme in Escherichia coli
-
truncated version expressed in Escherichia coli
-
TPH2, DNA and amino acid sequence determination and analysis, genotyping, expression of mutant Q468R in HeLa cells, overview
-
pBR322 containing the open reading frame of PTMO, PCR products inserted into the EcoRV site of pBluescript vector, expressed from vector pET 22b(+) in Escherichia coli BL21(DE3)
-
expression in HeLa cells
-
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
-
His-tagged enzyme, expression in Escherichia coli
O96370
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
TPH-1 mRNA levels are significantly decreased in the hypothalami of croaker exposed for 2 weeks to hypoxic conditions compared with those in fish exposed to normoxic conditions. Hypoxia causes a marked decline in hypothalamic TPH protein levels, which is associated with a 65% decrease in hypothalamic TPH enzyme activity and a 60% decrease in 5-hydroxytryptophan levels
B3VBU9, B3VBV0
TPH-2 mRNA levels are significantly decreased in the hypothalami of croaker exposed for 2 weeks to hypoxic conditions compared with those in fish exposed to normoxic conditions. Hypoxia causes a marked decline in hypothalamic TPH protein levels, which is associated with a 65% decrease in hypothalamic TPH enzyme activity and a 60% decrease in 5-hydroxytryptophan levels
B3VBU9, B3VBV0
TPH-1 mRNA is highly expressed in the total RNA extracted from the preoptic anterior hypothalamus and midbrain tegmentum compared with other brain areas
B3VBU9, B3VBV0
TPH-2 mRNA shows high expression in the preoptic anterior hypothalamus, midbrain tegmentum and cerebellum with optic tectum, compared with other brain areas
B3VBU9, B3VBV0
imipramine increases dorsal raphe TPH2 gene expression in a glucocorticoid-dependent manner, increases are due to relief of inhibitory glucocorticoid signaling
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A218C
-
a naturally occuring polymorphism associated with borderline personality disorder diagnosis, but not with suicidal behaviour, genotyping, overview
A218C
P17752
interaction between gene TPH1 218Ato C or rs1800532 polymorphism and gender in determining plasma TRP whereby presence of the 218C allele, in women, is associated with markedly reduced plasma tryptophan levels, overview
A328V
-
moderate loss-of-function effects in the catalytic and oligomerization domains
A779C
P17752, Q8IWU9
naturally occuring polymorphism in intron 7 of TPH1 is associated with alcoholic offenders
C164A/G170A
-
mutations represent differences between the human and chimpanzee enzyme, activity similar to wild-type
C164A/G170A/Q468R
-
mutations represent differences between the human and chimpanzee enzyme and a polymorphism at position 468 present in chimpanzees but not in humans. 1.4fold activity compared to wild-type
D479E
-
moderate loss-of-function effects in the catalytic and oligomerization domains
delta1-150
-
deletion of the N-terminal regulatory domain. Increased solubility when expressed in Escherichia coli.
delta1-150/421-444
-
deletion of the N-terminal regulatory domain and the C-terminal tetramerisation domain. Increased solubility when expressed in Escherichia coli. The mutant protein shows a 2fold increase of the Km for L-tryptophan and a 3fold decrease of the Km for (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
F313W
-
N-terminal truncated enzyme
F313W
-
F313W mutant shows no preference for tryptophan over phenylalanine as a substrate
L36P
-
properties affecting the regulatory domain are indistinguishable from the wild-type, severe alterations in secondary structure
P206S
Q8IWU9
a naturyll occuring rare, non-synonymous single nucleotide polymorphism rs17110563 showing significant association with bipolar disorder, reduced thermal stability and solubility of the mutated enzyme compared to the wild-type enzyme
P206S
-
moderate loss-of-function effects in the catalytic and oligomerization domains, severe alterations in secondary structure, reduced stability
P449R
Q8IWU9
reduced thermal stability compared to the wild-type enzyme, site-directed mutagenesis, the TPH2 genetic variant, shows comparable catalytic activity (Vmax) and solubility relative to the wild type, but has decreased thermal stability
R303W
-
has severely reduced solubility and is completely inactive, alteration in net charge
R441H
Q8IWU9
reduced solubility compared to the wild-type enzyme and reduced thermal stability. The mutant shows a 2fold lower Km for (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
R441H
Q8IWU9
a naturally occuring single nucleotide polymorphism
R441H
-
naturally occuring missense mutation
R441H
Q8IWU9
site-directed mutagenesis, the TPH2 genetic variant, shows had decreased activity, solubility and stability compared to the wild-type enzyme
R441H
-
moderate loss-of-function effects in the catalytic and oligomerization domains, alteration in net charge
R55C
-
properties affecting the regulatory domain are indistinguishable from the wild-type, alteration in net charge
S104A
-
site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme
S104E
-
site-directed mutagenesis of a phosphorylation site, the mutant is not activated by protein 14-3-3 in contrast to the wild-type enzyme
S19A
-
site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme
S19A
-
site-directed mutagenesis, the mutant is not phpsphorylated by calmodulin-dependent protein kinase II and not activates, but basal activity and catalytic function is unaltered
S19E
-
site-directed mutagenesis of a phosphorylation site, the mutant is not activated by protein 14-3-3 in contrast to the wild-type enzyme
S306A
-
site-directed mutagenesis of a putative phosphorylation site
S306E
-
site-directed mutagenesis of a putative phosphorylation site
S41Y
-
properties affecting the regulatory domain are indistinguishable from the wild-type
S99A
-
site-directed mutagenesis of a putative phosphorylation site
C110S/C112S
-
all cysteine residues of the regulatory domain mutated
C110S/C112S/C162S/C234S/C248S/C296S
-
six N-terminal-most cysteines mutated
C110S/C112S/C162S/C234S/C248S/C296S/C315S/C355S/C365S/C394S/C404S/C408S/C476S
-
all 13 cysteine residues mutated
C110S/C162S/C234S/C248S/C296S/C355S/C365S/C394S/C404S/C408S/C476S
-
mutant protein containing a single cysteine residue within the regulatory domain (Cys112) and within the catalytic core domain (Cys315)
C1473G
-
naturally occuring polymorphism of gene Tph2, C57Bl/6 and 129X1/SvJ mice are homozygous for the 1473C allele, whereas DBA/2 and BALB/cJ mice are homozygous for the 1473G allele, comparison of pulmonary hypertension and vascular remodeling of haplotypes, overview
C162S/C234S/C248S/C296S/C315S/C355S/C365S/C394S/C404S/C408S/C476S
-
all cysteine residues of the catalytic core domain mutated
C315S/C355S/C365S/C394S/C404S/C408S/C476S
-
seven C-terminal-most cysteines mutated
C476S
-
residue of the tetramerization domain
DELTA-C-terminal 24 residues
-
removed tetramerization domain
DELTA1-40
-
simulates tyrosine hydroxylase 1
P447R
Q8CGV2
the C1473G naturally occuring polymorphism in gene tph2 is the main factor mediating the genetically defined variability of tryptophan hydroxylase-2 activity in the mouse brain, phenotypes, overview
DELTA 1-101/DELTA last 28 residues
-
catalytic core
F241A
synthetic construct
-
drop in interaction energy of 58%
F241G
synthetic construct
-
loses 76% of the interaction energy
F241I
synthetic construct
-
drop in interaction energy of 4%, reduction in interaction for the isoleucine mutation may cause a reduction in the production of 5-hydroxy-L-tryptophan, and in turn, a reduction in serotonin. This may lead to onset of symptoms, such as anxiety, depression, and OCD
F241L
synthetic construct
-
retains the interaction energy necessary to keep protein function
F241Q
synthetic construct
-
retains the interaction energy necessary to keep protein function
F241Y
synthetic construct
-
retains the interaction energy necessary to keep protein function
additional information
A7VKD9
TPH knockout, by RNAi, animals shows reduced serotonin levels compared to wild-type animals
L36V
-
properties affecting the regulatory domain are indistinguishable from the wild-type
additional information
Q8IWU9
a naturally occuring mutation in exon 6, g.22879A-G, a single nucleotide polymorphism, causes truncation of the enzyme to the native short form of brain-specific isozyme TPH2, which causes impaired serotonin transmission and depression, phenotype, overview
additional information
P17752
A218C is a naturally occuring polymorphism in TPH1, genotyping in Korean population with major depressive disorder patients, remission rate to citalopram treatment was worse in MDD subjects with the TPH1 A/A and A/C genotypes than in those with the TPH1 C/C genotype, overview
additional information
-
additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing, isolation and analysis of a serotonergic gene polymorphism related to brain affective processing is the tryptophan hydroxylase-2 gene TPH2, TPH2 rs4570625 genotyping, behavioural phenotypes, overview
additional information
-
construction of a chimeric protein HA-TPH2-(1-41)-TPH1 composed of the first 41 amino acids of TPH2 appended to the N terminus of TPH1, the expression level of the chimeric protein is significantly decreased compared with TPH1 in HEK-293 and PC-12 cell lines and is more similar to that of TPH2
additional information
-
construction of various deletion mutants of TPH2: DN44, DC17, DC19,and DC51. Removal of 44 amino acids from the N-terminus of TPH2 results in a 3-4fold increased Vmax, which indicates a strong inhibitory function of this part on the enzymes activity. Deletion mutants DC17, DC19and DC51, which lack the putative C-terminal leucine zipper tetramerization domain, exist as monomeric enzymes
additional information
-
determination and analysis of single nucleotide polymorphisms in Japanese subjects, rs10741734, rs211102, rs10488683, rs9633898, rs1800532 and rs4537731, genotyping, analysis of correlations with schizophrenia in a case-control association study, and meta-analysis, no significant associations between the polymorphisms or haplotypes of TPH1 and schizophrenia in the Japanese subjects, but possible involvement of the TPH1 218A allele in susceptibility to schizophrenia, overview
additional information
P17752, Q8IWU9
determination and analysis of TPH2 polymorphisms rs10748185, rs2129575, rs1386495, rs1386494, and rs7305115 in terms of genotype, allele, and haplotype-based associations, neither single marker nor haplotype-based analysis shows significant associations between TPH2 and MD, genotyping, in this particular group of stress-induced depression patients TPH1 appears to be more relevant to MD pathogenesis than TPH2, overview
additional information
Q8IWU9
determination of several common and rare genetic variations, single nucleotide polymorphisms, in the TPH2 gene, e.g. of rs11178997 in the 5'-associated haplotype block, through a sequential sequencing and SNP-based genotyping, contribution of TPH2 genetic variability to the aetiology of bipolar affective disorder, BPAD, phenotypes, overview
additional information
Q8IWU9
effects of TPH2 mutations on their heterologous expression levels, solubility, thermal stability, secondary structure, and catalytic properties, overview
additional information
-
G703T and C218A are naturally occuring polymorphisms, genotyping of TPH1 and TPH2 in correlation to alcohol abuse, overview
additional information
-
gene TPH2, screening for naturally occuring polymorphisms associated with behavioural properties, e.g. attention, and intelligence, overview
additional information
-
genotyping of naturally occuring single nucleotide polymorphisms of TPH2 in brain tissues, identification of 27 mutations, the mutations causing allelicexpression imbalance are associated with depressiona nd suicide, overview
additional information
-
genotyping of TPH2 in depressive patients, the single nucleotide polymorphisms rs4448731 and rs4641527 significantly predict suicide, along with cluster B personality disorders and family history of suicide, overview
additional information
P17752, Q8IWU9
genotyping, in a particular group of stress-induced depression patients isozyme TPH1 appears to be more relevant to MD pathogenesis than isozyme TPH2, overview
additional information
Q8IWU9
naturally occuring single nucleotide polymorphisms rs4570625, rs1386494, rs10897346 and rs1487278 are associated with major depression and the patients carrying these mutations respond to therapy, determination of clinical and molecular predictors, overview
additional information
-
polymorphism rs11178997 of the TPH2 promoter significantly reduces TPH2 transcriptional activity by 7% in SHP-77 cells. 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, functional assays of TPH2 regulatory region variants, overview
additional information
P17752, Q8IWU9
screening for TPH2 polymorphisms in Han Chinese subjects, genotyping, haplotype frequency and association analysis, naturally occuring polymorphisms of TPH2 are A90G in the 5'-UTR of exon 1, C2755A in exon 2, C10662T in intron 4, G26270A in intron 5, G33775A in intron 6, G40237A in exon 7, A83610T in exon 9, and G93329A in the 3'-UTR of exon 11, overview
additional information
Q8IWU9
single nucleotide polymorphism, linkage disequilibrium, and haplotype studies on 353 alcohol-dependent patients of whom 102 individuals have a history of at least one suicide attempt and 305 healthy controls with 20 single nucleotide polymorphisms covering the entire gene region of TPH2. Neither single single nucleotide polymorphism nor haplotype analysis detect significant associations with alcohol dependence and/or suicidal behavior among alcohol-dependent patients, overview
additional information
Q8IWU9
the naturally occuring functional promoter polymorphism TPH2-703 G/T of the tryptophan hydroxylase 2 gene is involved in prefrontal and parietal regions are activated during working memory tasks, genotype groups of the -703 G/T: a significantly stronger activation of the TT genotype carriers in BA 6, BA 46, and BA 40 is visible in contrast to the GTand GG groups, no significant differences between the genotype groups with respect to age or gender, overview
additional information
-
specific activity is decreased for all mutations in the catalytic and oligomerization domains of TPH2. All TPH2 mutants appear to be more soluble in HEK-293 cells than in Escherichia coli, all variants are expressed as intact fusion proteins at high levels in Escherichia coli and are cleaved by tobacco etch virus protease
S99E
-
site-directed mutagenesis of a putative phosphorylation site
additional information
Q2HZ26
C74A and G223A are naturally occuring, nonsynonymous single nucleotide polymorphisms
G1473C
-
naturally occuring polymorphism, citalopram raises basal extracellular serotonin levels in DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele, but not in C57BL/6J and C57BL/6N mice carrying the 1473C allele, overview
additional information
-
construction of Tph1 knockout mutant mice, distal pulmonary vessel muscularization is less marked in Tph1-/- than in wild-type mice
additional information
-
generation of Tph1 homozygous null mice from a 129S5/SvEvBrd and C57BL/6J hybrid background
additional information
-
mice deficient in TPH1 and serotonin exhibit a reduced risk of thrombosis and thromboembolism, development of antithrombotic hammerhead miniribozymes with site-specific cleavage activity against short synthetic Tph1 RNA substrates targeting peripheral tryptophan hydroxylase, method development and evaluation, overview
Q486R
-
determination of a naturally occuring single nucleotide polymorphism at the exon 11 coding region that resulted in amino acid substitutions in the C-terminal domain, determination of allele frequency, the mutation is a gain -of-function mutation leading to 20% increased activity, comparison to rat and human TPH2s, overview
additional information
Q8CGU9
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
A7VKD9
a Dugesia japonica TPH antibody is a useful marker for serotonergic neurons in planarians
drug development
-
substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acids as novel TPH1 inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome
medicine
-
the two distinct serotonin systems in the brain (TPH2) and in the periphery (TPH1) can be targeted independently by pharmacological agents and new therapeutical options are available for psychiatric diseases on one side and disorders of haemostasis and the immune system on the other side, TPH2 is a good candidate gene for 5-hydroxytryptophan related psychiatric diseases such as bipolar affective disorders. The two distinnct serotonin systems in the brain (TPH2) and in the periphery (TPH1) can be targeted independently by pharmacological agents and new therapeutical options are available for psychiatric diseases on one side and disorders of haemostasis and the immune system on the other side
drug development
-
substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acids as novel TPH1 inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome
medicine
-
the serotonin transporter gene-linked promoter region 5-HTTLPR and tryptophan hydroxylase-2 genes act in concert to modulate the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders
additional information
-
enhancement of L-tryptophan hydroxylation activity of L-phenylalanine 4-hydroxylase from Chromobacterium violaceum using information on the crystal structures of aromatic amino acid hydroxylases including TPH