Two new tetrahydropterin intermediates in the adrenal medullary de novo biosynthesis of tetrahydrobiopterin

Abstract

Isolation of two kinetically competent tetrahydropterin intermediates on the de novo biosynthetic pathway to tetrahydrobiopterin is reported. The compounds were detected in HPLC chromatograms by electrochemical oxidation at 270 mv. The hydrodynamic voltamograms of the compounds are indistinguishable from those of tetrahydropterins . Both require Mg+ + for biosynthesis from dihydroneopterin triphosphate. One compound is produced in the absence of NADPH; the other requires NADPH for synthesis. Enzymatic conversion of the former into the latter intermediate requires NADPH. Conversion of either intermediate into tetrahydrobiopterin also requires NADPH. Mg+ +, which is required for the biosynthesis of the intermediates, is not needed for their conversion to tetrahydrobiopterin. Neither compound coelutes with 6-lactoyl tetrahydropterin, the tetrahydropterin analog of sepiapterin.