Pterin-dependent monooxygenase

The least understood aspect of NO synthases is the requirement for tetrahydrobiopterin, BH4, the same coenzyme required by the other pterin-dependent monooxygenases (Eq. 18-44). The presence of this coenzyme in the reduced BH4 form is essential for step a of Eq. 18-65 but not for step b. This suggests that in step a an organic peroxide might be generated by BH4 and used to form an oxo-iron hydroxylating reagent. 

The important metaboUsm of the neurotransmitters norepinephrine, epinephrine, dopa, and serotonin involves pterin-dependent monooxygenases. The direct biocatalytic hydroxylation of the aromatic amino acids phenylalanine, tyrosine, and tryptophane requires tetrahydrobiopterin and Fe as the cofactors [60]. The cleavage of unsaturated glyceryl ethers by glyceryl ether monooxygenase also requires tetrahydrobioterin as the cofactor [61]. 

Walsh C. Flavin- and pterin-dependent monooxygenases. In Enzymatic Reaction Mechanisms. San Francisco W. H. Freeman, 1979 Chapter 12. 

Important nonheme iron monooxygenases other than sMMO are pterin-dependent enzymes and isopenicillin N synthase. Three enzymes are known as the pterin-dependent monooxygenases phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH). These enzymes perform metabolically important transformations, e,g, for the biosynthesis of neurotransmitters, and catalyze the reactions shown in Fig. 8. 

Tetrahydrobiopterin (BPH4) is the natural cofactor required for the mammalian aromatic amino acid monooxygenases phenylalanine, tyrosine and tryptophan hydroxylase [4,89]. During the course of the reaction catalyzed by these enzymes, a molecule of oxygen is cleaved in order to hydroxylate the respective amino acid substrate. The remaining atom of oxygen is reduced to water at the expense of the cofactor, which is oxidized to the quinonoid form. Despite the many studies on the pterin-dependent hydroxylases, their precise mechanism of action is not well understood. This discussion will focus on mammalian phenylalanine hydroxylase (PAH), which has been favored for investigation due to its relative stability and ease of... 

The pterin-dependent amino acid hydroxylases (AAH) are a group of mononuclear, nonheme monooxygenases that catalyze the oxidation of aromatic amino acids necessary for the biosynthesis of a variety of neurotransmitters. " The three primary enzymes that have been... 

Figure 8. Reaction catalyzed by pterine-dependent non-heme iron monooxygenases [93].

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