8 Aromatic Amino Acid Hydroxylases

Abstract

Publisher Summary This chapter summarizes the physical and catalytical properties and the phosphorylation-mediated activation of the three aromatic amino acid hydroxylases within the context of the roles that these enzymes play in the organism. These three pterin-dependent enzymes are phenylalanine, tyrosine, and tryptophan hydroxylase. Phenylalanine hydroxylase phosphatase has been used to study in greater detail the relationship between the phosphate content of the hydroxylase and its BH4-dependent hydroxylase activity. Studies on the modulation of the activity of purified rat liver phenylalanine hydroxylase by in vitro phosphorylation and dephosphorylation have suggested that hydroxylase activity could be regulated in vivo by similar mechanisms. It is evident that phenylalanine hydroxylase can be phosphorylated by cAMP-dependent protein kinase in vivo. The activation of phenylalanine hydroxylase by glucagon has also been demonstrated in hepatocytes isolated from rats. It is found that glucagon increases the extent of phosphorylation of the hydroxylase. In contrast to phenylalanine hydroxylase that catalyzes the rate-limiting step in the pathway by which phenylalanine is catabolized, neither tyrosine nor tryptophan hydroxylases are involved in the catabolism of their respective amino acid substrates. Rather, the reactions that these enzymes catalyze are essential for the synthesis of neurotransmitters.