Phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase constitute a small family of monooxygenases that utilize tetrahydropterins as substrates. When from eukaryotic sources, these enzymes are composed of a homologous catalytic domain to which are attached discrete N-terminal regulatory domains and short C-terminal tetramerization domains, whereas the bacterial enzymes lack the N-terminal and C-terminal domains. Each enzyme contains a single ferrous iron atom bound to two histidines and a glutamate. Recent mechanistic studies have begun to provide insights into the mechanisms of oxygen activation and hydroxylation. Although the hydroxylating intermediate in these enzymes has not been identified, the iron is likely to be involved. Reversible phosphorylation of serine residues in the regulatory domains affects the activities of all three enzymes. In addition, phenylalanine hydroxylase is allosterically regulated by its substrates, phenylalanine and tetrahydrobiopterin.
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