Tyrosine hydroxylase (TH) is found in all cells that synthesize catecholamines and is a mixed-function oxidase that uses molecular oxygen and tyrosine as its substrates and biopterin as its cofactor. TH is a homotetramer, each subunit of which has a molecular weight of approximately 60,000. It catalyzes the addition of a hydroxyl group to themeta position of tyrosine, thus forming 3,4-dihydroxy-l-phenylalanine (l-DOPA).
TH can also hydroxylate phenylalanine to form tyrosine, which is then converted to l-DOPA; this alternative synthetic route may be of significance in patients affected with phenylketonuria, a condition in which phenylalanine hydroxylase activity is depressed. TH has a Km for tyrosine in the micromolar range. As a result, it is virtually saturated by the high tissue concentrations of endogenous tyrosine.
The cofactor, biopterin, may be at subsaturating concentrations within catecholamine-containing neurons and, thus, may play an important role in regulating NE biosynthesis. TH is primarily a soluble enzyme; however, interactions with membrane constituents, such as phosphatidylserine, or with polyanions, such as heparin sulfate, have been shown to alter its kinetic characteristics. Analogs of tyrosine, such as α-methyl-p-tyrosine (AMPT), are competitive inhibitors of TH. Sequence analysis reveals consensus sequences for phosphorylation primarily in the N-terminal portion of the molecule. The gene reveals considerable sequence homology with phenylalanine hydroxylase and tryptophan hydroxylase. (source)