Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.14.16.2

Official Name

tyrosine 3-monooxygenase

Name from literature

tyrosine hydroxylase

Pathway from literature

the catecholamine biosynthetic pathway

Pathway from KEGG

Human Diseases; Neurodegenerative Diseases; Parkinson's disease; map05020

Amino Acid Metabolism; Tyrosine metabolism; map00350

Organisms

Mouse (10090)

Genome localization

7 F5|7 69.2 cM[21823 ],

Comments

The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA carboxylase] kinase. The 4a-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.

Rate-limiting Description

"In particular, we focused on the rate-limiting catecholamine-synthesizing enzyme tyrosine hydroxylase (TH)." (17105912)

"Tyrosine 3-monooxygenase (tyrosine hydroxylase, TH) catalyzes the initial and rate-limiting step in the catecholamine biosynthesis." (16105653)

"Tyrosine hydroxylase is the rate-limiting enzyme in the biosynthesis of catecholamines." (16515541)

"Choline uptake by the high affinity choline transporter (CHT) is the rate-limiting step in acetylcholine synthesis." (16278103)

"To investigate the possibility that these two factors are functionally interrelated, we investigated the potential role of the androgen receptor (AR) on transcriptional activity of the tyrosine hydroxylase (TH) gene that encodes the rate-limiting enzyme of the dopamine biosynthesis pathway." (16356647)

"Tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2, TH) is the rate-limiting enzyme in the biosynthesis of catecholamine neurotransmitters, dopamine (DA), noradrenaline (NE), and adrenaline, in the neurons." (17054915)

"Among the most significantly up-regulated genes in DGKepsilon (+/+) mice included those encoding the inducible prostaglandin synthase cyclooxygenase-2 (COX-2) and tyrosine hydroxylase (TH), also known as tyrosine 3-monooxygenase, the rate-limiting enzyme of catecholamine biosynthesis." (16137646)

"TH, the rate-limiting enzyme in dopamine synthesis, converts tyrosine to l-dihydroxyphenylalanine (L-DOPA), which is then converted to dopamine by the enzyme, aromatic amino acid decarboxylase (AADC)." (16981894)

"One of the possibly mutated genes in DOPA-responsive dystonia (DRD, Segawa's disease) is the gene encoding GTP cyclohydrolase I, which is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis." (16135092)

Regulatory Information

Upstream transcription factor

11835;57320

Regulatory type

Detail

phosphorylation;

P24529

phosphorylation;

P24529:from_uniprot:19_Phosphoserine; by CaMK2

phosphorylation;

P24529:from_uniprot:31_Phosphoserine

phosphorylation;

P24529:from_uniprot:40_Phosphoserine; by PKA

phosphorylation;

"expression in the Purkinje cells of ataxic mutants abnormally increases without activation of this enzyme by phosphorylation" (15008900)

phosphorylation;

"data suggest that cyclin-dependent kinase 5 (cdk5) phosphorylation of tyrosine hydroxylase(TH) is an important regulator of TH activity through stabilization of TH protein levels" (15471880)

transcriptional factor;"DJ-1(57320),AR(11835)"

"Based on these data, we propose that AR activates TH gene expression and that DJ-1 may modulate AR activity as a transcriptional co-repressor." (16356647)

phosphorylation;

"alpha-synuclein is involved in the ability of tyrosine to enhance tyrosine hydroxylase phosphorylation or hinder its inactivation during accelerated neuronal activity." (16412098)

Gene ontology

Gene ontology

GO:0004511 (F) tyrosine 3-monooxygenase activity [P24529 ];
GO:0042136 (P) neurotransmitter biosynthetic process [P24529 ];
GO:0043204 (C) perikaryon [P24529 ];
GO:0007613 (P) memory [P24529 ];
GO:0042755 (P) eating behavior [P24529 ];
GO:0042462 (P) eye photoreceptor cell development [P24529 ];
GO:0007601 (P) visual perception [P24529 ];
GO:0006585 (P) dopamine biosynthetic process from tyrosine [P24529 ];
GO:0007617 (P) mating behavior [P24529 ];
GO:0007626 (P) locomotory behavior [P24529 ];
GO:0007507 (P) heart development [P24529 ];
GO:0001963 (P) synaptic transmission, dopaminergic [P24529 ];
GO:0007612 (P) learning [P24529 ];
GO:0005634 (C) nucleus [P24529 ];
GO:0008016 (P) regulation of heart contraction [P24529 ];
GO:0048596 (P) embryonic camera-type eye morphogenesis [P24529 ];
GO:0055114 (P) oxidation reduction [P24529 ];

Links

SwissProt

P24529

Entrez Gene

21823



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  Last Modified: 2009-03-24  
  Design by Zhao Min