Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3, 4-dihydroxyphenylalanine. It does so using molecular oxygen, as well as iron, L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine and epinephrine. Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines, in humans, tyrosine hydroxylase is encoded by the TH gene, and the enzyme is present in the central nervous system, peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of amino acid hydroxylases. Tyrosine hydroxylase catalyzes the reaction in which L-tyrosine is hydroxylated in the position to obtain L-3. The enzyme is an oxygenase which means it uses oxygen to hydroxylate its substrates. One of the atoms in O2 is used to hydroxylate the tyrosine molecule to obtain L-DOPA. The AAAHs converts the cofactor 5,6,7, 8-tetrahydrobiopterin into tetrahydrobiopterin-4a-carbinolamine, under physiological conditions, 4a-BH4 is dehydrated to quinonoid-dihydrobiopterin by the enzyme pterin-4a-carbinolamine dehydrase and a water molecule is released in this reaction. Then, the NADH dependent enzyme dihydropteridine reductase converts q-BH2 back to BH4, each of the four subunits in tyrosine hydroxylase is coordinated with an iron atom presented in the active site. The oxidation state of this atom is important for the catalytic turnover in the enzymatic reaction. If the iron is oxidized to Fe, the enzyme is inactivated, the product of the enzymatic reaction, L-DOPA, can be transformed to dopamine by the enzyme DOPA decarboxylase. Dopamine may be converted into norepinephrine by the enzyme dopamine β-hydroxylase, since L-DOPA is the precursor for the neurotransmitters dopamine, noradrenaline and adrenaline, tyrosine hydroxylase is therefore found in the cytosol of all cells containing these catecholamines. This initial reaction catalyzed by tyrosine hydroxylase has been shown to be the limiting step in the production of catecholamines. The enzyme is specific, not accepting indole derivatives - which is unusual as many other enzymes involved in the production of catecholamines do. Tryptophan is a substrate for tyrosine hydroxylase, however it can hydroxylate L-phenylalanine to form L-tyrosine. The enzyme can then further catalyze L-tyrosine to form L-DOPA, tyrosine hydroxylase may also be involved in other reactions as well, such as oxidizing L-DOPA to form 5-S-cysteinyl-DOPA or other L-DOPA derivatives. Tyrosine hydroxylase is a tetramer of four identical subunits, each subunit consists of three domains. At the carboxyl terminal of the peptide chain theres a short alpha helix domain that allows tetramerization, the central ~300 amino acids make up a catalytic core, in which all the residues necessary for catalysis are located, along with a non-covalently bound iron atom
Tyrosine hydroxylase from rat showing two of its domains, the tetramerization domain (pink) and the catalytic domain (blue). The regulatory domain (not shown) would sit somewhere on the right hand side of the image where also the enzyme's substrate would enter from.
Tyrosine hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis