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Literature summary extracted from

  • Thoeny, B.; Calvo, A.C.; Scherer, T.; Svebak, R.M.; Haavik, J.; Blau, N.; Martinez, A.
    Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase (2008), J. Neurochem., 106, 672-681.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.16.2 enzyme expression by in vitro transcription-translation using a rapid translation system with enhanced Escherichia coli lysate and radio-labeled L-Met, tetrahydrobioterin increases the enzyme protein yield Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.14.16.2 L205P the mutant is associated with recessively inherited L-DOPA-responsive infantile parkinsonism, the mutation reduces the activity and stability of the protein in cells and in vitro expression systems, being considered a misfolding mutation Homo sapiens

General Stability

EC Number General Stability Organism
1.14.16.2 binding of inhibitor dopamine and of cofactor tetrahydrobioterin stabilizes the enzyme Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.16.2 (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin i.e. BH4, cofactor, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, competitive inhibition, synergistically with DTT Homo sapiens
1.14.16.2 dopamine feedback inhibitor and catecholamine product, binding inhibits and stabilizes the enzyme, reversible and competitive inhibition with respect to tetrahydrobiopterin Homo sapiens
1.14.16.2 DTT inactivates the enzyme, synergistically with tetrahydrobiopterin Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.14.16.2 additional information
-
 additional information both the cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin and the feedback inhibitor dopamine increase the kinetic stability of human isozyme 1 in vitro Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.14.16.2 58000
-
 x * 58000, recombinant enzyme, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.16.2 L-tyrosine + tetrahydrobiopterin + O2 Homo sapiens rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, enzyme defects are associated with L-DOPA responsive and non-responsive dystonia and infantile parkinsonism, overview 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.16.2 Homo sapiens
-
 isozyme TH 1
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.16.2 brain
-
 Homo sapiens
-
1.14.16.2 neuron
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.16.2 L-tyrosine + tetrahydrobiopterin + O2
-
 Homo sapiens 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
 ?
1.14.16.2 L-tyrosine + tetrahydrobiopterin + O2 rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, enzyme defects are associated with L-DOPA responsive and non-responsive dystonia and infantile parkinsonism, overview Homo sapiens 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
 ?

Subunits

EC Number Subunits Comment Organism
1.14.16.2 ? x * 58000, recombinant enzyme, SDS-PAGE Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.14.16.2 tyrosine hydroxylase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.14.16.2 25
-
 assay at, recombinant enzyme Homo sapiens
1.14.16.2 30
-
 assay at, crude brain enzyme extract Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.16.2 7
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.16.2 (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin i.e. BH4, complex regulation by the cofactor including both enzyme inactivation and conformational stabilization, competitive inhibition Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.14.16.2 0.07
-
 (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin pH 7.0, 25°C, versus (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin Homo sapiens