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Literature summary for 1.14.16.2 extracted from

  • Scholz, J.; Toska, K.; Luborzewski, A.; Maass, A.; Schuenemann, V.; Haavik, J.; Moser, A.
    Endogenous tetrahydroisoquinolines associated with Parkinsons disease mimic the feedback inhibition of tyrosine hydroxylase by catecholamines (2008), FEBS J., 275, 2109-2121.
    View publication on PubMed

General Stability

General Stability Organism
catecholamine binding improves tyrosine hydroxylase's resistance to proteolysis Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Catecholamines e.g. dopamine, feedback inhibition, phosphorylation by protein kinase A at Ser40, the most prominent of these regulatory sites, increases the dissociation rate of bound catecholamine inhibitors Homo sapiens
dopamine binds to the iron ion at the active site Homo sapiens
additional information no inhibition by nonhydroxylated N-methyl-1,2,3,4-tetrahydroisoquinoline Homo sapiens
N-methyl-norsalsolinol noncompetitive with respect to L-tyrosine, N-methyl-norsalsolinol and related tetrahydroisoquinolines accumulate in the nigrostriatal system of the human brain and are increased in the cerebrospinal fluid of patients with Parkinson’s disease Homo sapiens
N-methyl-salsolinol
-
Homo sapiens
norsalsolinol N-methyl-norsalsolinol and related tetrahydroisoquinolines accumulate in the nigrostriatal system of the human brain and are increased in the cerebrospinal fluid of patients with Parkinson’s disease Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ localized at the active site, the ferric is the inactive state, modelling of catecholamine and 6,7-dihydroxylated tetrahydroisoquinoline inhibitor docking to the active site Fe2+, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-tyrosine + tetrahydrobiopterin + O2 Homo sapiens key enzyme in dopamine synthesis, negative catecholamine end-product regulation, overview 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
isozymes TH1 and TH4
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein enzyme activation by reversible phosphorylation, phosphorylation by protein kinase A at Ser40, the most prominent of these regulatory sites, increases the dissociation rate of bound catecholamine feedback inhibitors Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-tyrosine + tetrahydrobiopterin + O2
-
Homo sapiens 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
?
L-tyrosine + tetrahydrobiopterin + O2 key enzyme in dopamine synthesis, negative catecholamine end-product regulation, overview Homo sapiens 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
?

Synonyms

Synonyms Comment Organism
tyrosine hydroxylase
-
Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
37
-
5 h, stable, catecholamine, N-methyl-norsalsolinol, or norsalsolinol binding increases the thermal stability of tyrosine hydroxylase Homo sapiens

Cofactor

Cofactor Comment Organism Structure
tetrahydrobiopterin
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0002
-
-
Homo sapiens dopamine
0.0003
-
-
Homo sapiens N-methyl-norsalsolinol
0.004
-
-
Homo sapiens N-methyl-salsolinol
0.01
-
-
Homo sapiens norsalsolinol