Tyrosine 3-monooxygenase (TH) (TH)

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamines, including dopamine, norepinephrine, and epinephrine [1.1.1, 1.3.1]. It catalyzes the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) using tetrahydrobiopterin (BH4) as a cofactor and molecular oxygen [1.1.1, 1.4.2]. The enzyme is primarily expressed in the central nervous system, sympathetic postganglionic neurons, and the adrenal medulla [1.1.1, 1.3.2]. Dysregulation or deficiency of TH is linked to several neurological and neuropsychiatric disorders, most notably Parkinson's disease and Segawa syndrome [1.1.1, 1.3.2]. Pharmacological modulation of TH, such as inhibition by metyrosine, is used clinically to manage conditions like pheochromocytoma by reducing catecholamine overproduction [1.3.4]. Because of its central role in neurotransmitter synthesis, it remains a critical focus for therapeutic intervention in movement disorders and autonomic dysfunction [1.2.1, 1.3.3].

Other names

Tyrosine hydroxylaseTyrosine 3-hydroxylaseTYHDYT14DYT5bL-tyrosine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Metyrosine acts as a competitive inhibitor of tyrosine hydroxylase by competing with the substrate L-tyrosine for the catalytic active site [1.3.4]. This leads to a reduction in the synthesis of L-DOPA and subsequent catecholamines [1.1.1].