Tyrosine Hydroxylase. the Initial Step in Norepinephrine Biosynthesis.

After demonstration of the decarboxylation of 3,4-dihydroxyphenylalanine (dopa)’ to dopamine (I), the pathway for biosynthesis of norepinephrine shown in Fig. 1 was proposed. Although evidence for this pathway was well established by isot,opic procedures (2, 3), it was not until 1960 that Levin, Levenberg, and Kaufman (4) succeeded in isolating and characterizing the third enzyme in the series, dopamine-B-oxidase (@hydroxylase). The enzyme responsible for converting tyrosine to dopa has, however, proved elusive. The enzyme tyrosinase was considered in this role, but no evidence for it could be obtained in sympathetically innervated tissues. Reports of the enzymatic conversion of tyrosine to catecholamines by tissue slices and minces have generally been unconvincing owing to large and variable blanks with boiled preparations (5, 6). It has now been possible to demonstrate that brain, adrenal medulla, and sympathetically innervated tissues contain a specific hydroxylase that catalyzes the conversion of L-tyrosine to dopa. A short report on the properties of a particle-bound preparation from brain has already appeared (7). The present communication describes the isolation, purification, and charact#erization of a soluble tyrosine hydroxylase from beef adrenal medulla. The soluble tyrosine hydroxylase requires for activity tetrahydropteridine derivatives comparable to those previously observed for phenylalanine hydroxylase (8).