Anti-Tyrosine Hydroxylase

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of the catecholamines dopamine, epinephrine and norepinephrine. Therefore the regulation of the TH enzyme represents the central means for controlling the synthesis of these important catecholamines. FUNCTION: Plays an important role in the physiology of adrenergic neurons. CATALYTIC ACTIVITY: L-tyrosine + tetrahydrobiopterin + O2 = 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin. COFACTOR: Fe(2+) ion. ENZYME REGULATION: Phosphorylation leads to an increase in the catalytic activity. PATHWAY: Catecholamine biosynthesis; first step. SUBUNIT: Homotetramer. PTM: In vitro, phosphorylation of Ser-19 increases the rate of Ser-40 phosphorylation, which results in enzyme opening and activation. SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. The presence of different DNA sequences at the TH locus confers susceptibility to various disorders of the brain including manic-depression and schizophrenia. Parkinson's disease is also considered a TH deficiency as low dopamine levels are a consistent neurochemical abnormality.