Phenylalanine Hydroxylase, Tyrosine Hydroxylase, and Tryptophan Hydroxylase

There are four enzymes that utilize reduced pteridine as an electron donor and incorporate one atom of oxygen into their substrates. They are phenylalanine 4-monooxygenase (phenylalanine hydroxylase, PAH, EC 1.14.16.l), tyrosine 3-monooxygenase (tyrosine hydroxylase, TH, EC 1.14.16.2), anthranilate 3-monooxygenase (EC 1.14.16.3), and tryptophan 5-monooxygenase (tryptophan hydroxylase, TPH, EC 1.14.16.4). All four enzymes are also known as iron-proteins since they require iron for enzymatic actrvity. With the exception of anthranilate hydroxylase, these enzymes have been extensively studied. The present chapter concentrates on PAH, TH, and TPH, stressing recent work on biochemical and molecular biological properties, regulation, purification procedures, and methods for determination of enzyme activity. Since a number of excellent reviews for these enzymes have been published recently (Hamon et al., 1981 ; Kuhn and Lovenberg, 1982 ; Masserano and Weiner, 1983 ;Shiman, 1985 ), the present chapter avoids unnecessary repetition of data already presented. Classical reaction mechanisms, kinetic properties, anatomical and histochemical analyses, and pharmacological studies on the reaction products, e.g., DOPA, dopamine, 5-hydroxytryptophan, and serotonin, are not included in this chapter.