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Literature summary for 1.14.16.2 extracted from

  • Gordon, S.L.; Quinsey, N.S.; Dunkley, P.R.; Dickson, P.W.
    Tyrosine hydroxylase activity is regulated by two distinct dopamine-binding sites (2008), J. Neurochem., 106, 1614-1623.
    View publication on PubMed
Search for more literature for 1.14.16.2

Activating Compound

Activating Compound Comment Organism Structure
additional information phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme, the low-affinity dopamine-binding site is able to regulate tyrosine hydroxylase activity in both the non-phosphorylated and pSer40 forms of the enzyme, with dissociation of dopamine from the site increasing activity 12fold and 9fold respectively Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
adrenaline
-
 Rattus norvegicus
dopamine binding kinetics and regulatory function, overview, phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme. Binding of dopamine to the high-affinity site also decreases Vmax and increases the Km for the cofactor tetrahydrobiopterin, while binding of dopamine to the low affinity site regulates tyrosine hydroxylase activity by increasing the Km for tetrahydrobiopterin Rattus norvegicus
noradrenaline
-
 Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetics analysis, overview Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Rattus norvegicus 5829
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-tyrosine + tetrahydrobiopterin + O2 Rattus norvegicus the rate-limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of residue Ser40. Phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme, regulation mechanism overview 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
 ?

Organism

Organism UniProt Comment Textmining
Rattus norvegicus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein phosphorylation of Ser40 activtes the enzyme by reversing the inhibition by dopamine binding Rattus norvegicus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-tyrosine + tetrahydrobiopterin + O2
-
 Rattus norvegicus 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
 ?
L-tyrosine + tetrahydrobiopterin + O2 the rate-limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of residue Ser40. Phosphorylation of Ser40 abolishes the binding of dopamine to a high affinity site on the enzyme, thereby increasing the activity of the enzyme, regulation mechanism overview Rattus norvegicus 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
 ?

Synonyms

Synonyms Comment Organism
tyrosine hydroxylase
-
 Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25 30 assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
tetrahydrobiopterin binding of dopamine to the high-affinity site of the enzyme decreases Vmax and increases the Km for the cofactor tetrahydrobiopterin, while binding of dopamine to the low affinity site regulates tyrosine hydroxylase activity by increasing the Km for tetrahydrobiopterin Rattus norvegicus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
 additional information inhibition kinetics Rattus norvegicus