Tyrosine 3-hydroxylase

Tyrosine 3-hydroxylase (also known as TH) is an enzyme that in humans is encoded by the TH gene. It is one of the several biochemical enzymes involved in the process of neurotransmitter synthesis.

Function

Tyrosine 3-hydroxylase is the first and rate-limiting enzyme involved in the biosynthesis of the catecholamines dopamine, norepinephrine, and epinephrine. It catalyzes the conversion of L-tyrosine to L-DOPA (L-3,4-dihydroxyphenylalanine), a precursor of dopamine.

Structure

The TH enzyme is a tetramer composed of four identical subunits. Each subunit is composed of three domains: an N-terminal regulatory domain, a central catalytic domain, and a C-terminal tetramerization domain.

Regulation

The activity of tyrosine 3-hydroxylase is regulated on several levels. It is subject to allosteric regulation, covalent modification, and changes in gene expression. The enzyme is activated by phosphorylation, a process that is regulated by a number of kinases and phosphatases.

Clinical significance

Mutations in the TH gene are associated with a number of neurological disorders, including Segawa's syndrome, tyrosine hydroxylase deficiency, and certain forms of Parkinson's disease.

See also

• Tyrosine hydroxylase
• Catecholamine
• Dopamine
• Norepinephrine
• Epinephrine