biopterin-dependent aromatic amino acid hydroxylase biopterin-dependent aromatic amino acid hydroxylase biopterin-dependent aromatic amino acid hydroxylases (aaah) are a family of aromatic amino acid hydroxylase enzymes which includes phenylalanine 4-hydroxylase (ec 1.14.16.1), tyrosine 3-hydroxylase (ec 1.14.16.2), and tryptophan 5-hydroxylase (ec 1.14.16.4). these enzymes primarily hydroxylate the amino acids l-phenylalanine, l-tyrosine, and l-tryptophan, respectively. biopterin_hcrystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase (fe(ii)) complexed with tetrahydrobiopterin and norleucineidentifierssymbolbiopterin_hpfampf00351interproipr019774prositepdoc00316scop21toh / scope / supfamcddcd00361available protein structures:pfam structures / ecod pdbrcsb pdb; pdbe; pdbjpdbsumstructure summary the aaah enzymes are functionally and structurally related proteins which act as rate-limiting catalysts for important metabolic pathways. each aaah enzyme contains iron and catalyzes the ring hydroxylation of aromatic amino acids using tetrahydrobiopterin (bh4) as a substrate. the aaah enzymes are regulated by phosphorylation at serines in their n-termini. role in metabolism in humans, phenylalanine hydroxylase deficiency can cause phenylketonuria, the most common inborn error of amino acid metabolism. phenylalanine hydroxylase catalyzes the conversion of l-phenylalanine to l-tyrosine. tyrosine hydroxylase catalyzes the rate-limiting step in catecholamine biosynthesis: the conversion of l-tyrosine to l-dopa. similarly, tryptophan hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of l-tryptophan to 5-hydroxy-l-tryptophan. biosynthetic pathways for catecholamines and trace amines in the human brain l-phenylalanine l-tyrosine l-dopa epinephrine phenethylamine p-tyramine dopamine norepinephrine n-methylphenethylamine n-methyltyramine p-octopamine synephrine 3-methoxytyramine aadc aadc aadc primarypathway pnmt pnmt pnmt pnmt aaah aaah braincyp2d6 minorpathway comt dbh dbh in humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid l-phenylalanine. structure it has been suggested that the aaah enzymes each contain a conserved c-terminal catalytic (c) domain and an unrelated n-terminal regulatory (r) domain. it is possible that the r protein domains arose from genes that were recruited from different sources to combine with the common gene for the catalytic core. thus, by combining with the same c domain, the proteins acquired the unique regulatory properties of the separate r domains.