Tyrosine Hydroxylase

Tyrosine hydroxylase (TyrH, TH) is a rate-limiting enzyme in catecholamine biosynthesis and belongs to the family of aromatic amino acid hydroxylases. Tyrosine hydroxylase uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to dopamine. The amino-terminal 150 amino acids of tyrosine hydroxylase form a domain whose structure is involved in regulating the activity of the enzyme. Regulation involves phosphorylation by multiple kinases on 4 different serine residues and dephosphorylation by 2 phosphatases. Tyrosine hydroxylase is inhibited by catecholamine neurotransmitters in a feedback manner. Dopamine competes with tetrahydrobiopterin for binding to tyrosine hydroxylase and interacts with the R domain. Tyrosine hydroxylase activity is regulated by protein-protein interactions with enzymes in the same pathway or the tetrahydrobiopterin pathway, structural proteins that are thought to be chaperones in mediating the oxidative state of neurons, and proteins that transfer dopamine to secretory vesicles. Tyrosine hydroxylase is modified in the presence of NO. Tyrosine hydroxylase expression maintains dopamine synthesis. Tyrosine hydroxylase is severely lost in Parkinson's disease and slightly lost in Alzheimer's disease.