Biological Information

Background Information:

Tyrosine hydroxylase (tyrosine-3-monooxygenase, tyrosine oxidase, E.E.1.14.13.41) which catalyzes the hydroxylation of tyrosine is generally regarded as a rate-limiting step in the biosynthesis of catecholamines. The enzyme is activated following stimulation of adrenergic nerves or the adrenal medulla. Tyrosine hydroxylase is a substrate for cyclic AMP-dependent kinase, and kinase-catalyzed phosphorylation is associated with increased hydroxylase activity. The enzyme is also a substrate for Ca2+-activated protein kinases. In addition, tyrosine hydroxylase is inhibited by catechol compounds in a manner that is competitive with its pterin cofactor, tetrahydrobiopterin. It is thus subject to end-producr feedback inhibition. A potent and selective inhibitor of this enzyme may prove useful as a therapeutic agent in the treatment of hypertension as well as schizophrenia and tardive dyskinesia.

Family:

Neurotransmitter Metabolism

Sub Family:

Amino Acid Hydroxylase

Protein Name:

Tyrosine Hydroxylase

Uniprot Number:

P07101

Protein Aliases:

tyrosine 3-monooxygenase

Gene Name:

TH

Gene ID:

7054

Gene Aliases:

DYT5b

Accession Number:

NM_012740

Organism:

Rat

Construct Details:

Endogenous

Assay Information

Assay Type:

Biochemical

Assay Sub Type:

Enzymatic

Functional Mode:

Antagonist

Detection Method:

Radiometry

Measured Response:

Scintillation

Testing Information

Procedure Summary:

Rat brain tyrosine hydroxylase is used. Test compound and/or vehicle is preincubated with 4.9 mg/ml enzyme‡ in modified MES buffer pH 6.0 for 15 minutes at 37⁰C. The reaction is initiated by addition of 10 μM L-tyrosine and 0.5 μCi L-[3,5-3H]Tyrosine for another 20 minute incubation period and terminated by further addition of 1 N HCl. An aliquot is removed and counted to determine the amount of [3H]H2O formed. Compounds are screened at 10 μM.

Substrate:

10 µM L-[3, 5-³H]Tyrosine + L-Tyrosine

Incubation:

20 min at 37°C

Control Inhibitor:

Alpha-Methyl-L-P-Tyrosine

Criteria For Significance:

≥ 50% of max stimulation or inhibition

Test Concentration / Dose:

Suggested concentration for initial testing is 10 uM

Test Sample Requirements:

Minimum for 1) Screen: 25 μl of 10 mM stock -OR- 1 mg (pre-weighed). 2) Dose Response: 60 μl of 10 mM stock -OR- 1 mg (pre-weighed).

Minimum Order Quantity:

2

Turnaround Time

Standard:

15 Business Days

Reference Compound Data

PubChem ID

439744

Name

3-Iodo-L-tyrosine

Measurement

0.6μM -

PubChem ID

441350

Name

Alpha-Methyl-L-P-Tyrosine

Measurement

2μM -

Clinical Relevance

Therapeutic Area:

CNS/Addiction/Pain

Additional Information

Brand:

LeadHunter

Testing Location:

Taiwan - Taipei