The aromatic amino acid hydroxylases.
The enzymes phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase constitute the family of pterin-dependent aromatic amino acid hydroxylases. Each enzyme catalyzes the hydroxylation of the aromatic side chain of its respective amino acid substrate using molecular oxygen and a tetrahydropterin as substrates. Recent advances have provided insights into the structures, mechanisms, and regulation of these enzymes. The eukaryotic enzymes are homotetramers comprised of homologous catalytic domains and discrete regulatory domains. The ligands to the active site iron atom as well as residues involved in substrate binding have been identified from a combination of structural studies and site-directed mutagenesis. Mechanistic studies with nonphysiological and isotopically substituted substrates have provided details of the mechanism of hydroxylation. While the complex regulatory properties of phenylalanine and tyrosine hydroxylase are still not fully understood, effects of regulation on key kinetic parameters have been identified. Phenylalanine hydroxylase is regulated by an interaction between phosphorylation and allosteric regulation by substrates. Tyrosine hydroxylase is regulated by phosphorylation and feedback inhibition by catecholamines.
Fitzpatrick
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PF
Department of Biochemistry and Biophysics, Texas A&M University, College Station 77843-2128, USA.
D000598:Amino Acids, Cyclic / Q000378:metabolism; D001665:Binding Sites; D015971:Gene Expression Regulation, Enzymologic; D006900:Hydroxylation; D008958:Models, Molecular; D019159:Nonheme Iron Proteins / Q000737:chemistry / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000737:chemistry / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000737:chemistry / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000378:metabolism*
D000598:Amino Acids, Cyclic; D019159:Nonheme Iron Proteins; D010651:Phenylalanine Hydroxylase; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase