In vivo enhancement of tyrosine hydroxylation in rat striatum by tetrahydrobiopterin

Abstract

THE hydroxylation of tyrosine, the rate-limiting step in the biosynthesis of catecholamines in vivo¹, depends on various factors: the concentration of apoenzyme and of cofactor (5,6,7,8-tetrahydrobiopterin, BH₄), the availability of molecular oxygen^2–4 and the activity of the system reducing the oxidised pteridine (dihydropteridine reductase⁵). Calculations based on the rate of tyrosine hydroxylation in vitro and on the cofactor concentration in brain suggested that the latter might be limiting^6,7, although its concentration at the enzyme site is not known. Similar conclusions were reached in experiments with cultures of sympathetic chain of chicks in which addition of biopterin increased the catecholamine content⁸. But no evidence exists for a possible role of BH₄ as limiting factor of tyrosine hydroxylation in vivo. We describe here the in vivo effect of BH₄, the natural cofactor of tyrosine hydroxylase⁹, on dopamine formation in rat striatum.