Comparative studies on the structure of human tyrosine hydroxylase with those of the enzyme of various mammals.

1. Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in catecholamine biosynthesis. 2. The structures of TH from various species have been elucidated. 3. We have cloned and determined the sequences of four types of human TH cDNA and human TH genomic DNA. 4. We have compared the amino acid sequences of TH from various species. 5. The results indicate that the amino acid sequences of TH are highly conserved among various species, and that TH consists of the regulatory domain containing serine residues which are phosphorylated by protein kinases and of the catalytic domain where the substrates, tyrosine and oxygen, and the cofactor, tetrahydrobiopterin, are bound. 6. Comparison of amino acid sequences among TH from various species can give us useful information on the functional importance of each amino acid residue.