Dihydropteridine reductase: implication on the regulation of catecholamine biosynthesis

The low tissue concentrations of tetrahydrobiopterin, as well as the antagonism between the catecholamine feedback inhibition of tyrosine hydroxylase and the reduced cofactor concentrations, suggest that dihydropteridine reductase may play an important role in the regulation of catecholamine biosynthesis. The interaction of the different components involved in the hydroxylation of tyrosine was studied in vitro in a complex system composed of tyrosine hydroxylase, dihydropteridine reductase, and the different cofactors. This system has several important characteristics: (a) the rate of dihydroxyphenylalanine formation can be controlled by the concentration of dihydropteridine reductase; (b) low concentrations of catecholamines (2 x 10(-5) M) can produce a marked inhibition of tyrosine hydroxylase activity; and (c) the catecholamine feedback-inhibition of tyrosine hydroxylase can be antagonized by increasing concentrations of dihydropteridine reductase. The properties of the in vitro tyrosine hydroxylase-dihydropteridine reductase system suggest that dihydropteridine reductase may have an important role in vivo in the determination of the rates of dihydroxyphenylalanine formation and on the effectiveness of the catecholamine feedback-inhibition of tyrosine hydroxylase activity.