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 (), tyrosine 3-hydroxylase (), and tryptophan 5-hydroxylase (). These enzymes primarily hydroxylate the amino acids L-phenylalanine, L-tyrosine, and L-tryptophan, respectively. 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  to . Tyrosine hydroxylase catalyzes the rate-limiting step in catecholamine biosynthesis: the conversion of  to . Similarly, tryptophan hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of  to . 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. References

Protein domains