BH4-Biosynthesis: 1H-NMR Evidence for the Pyruvoyl-tetrahydropterin-synthase Catalyzed Formation of 6-Pyruvoyl-tetrahydropterin from Dihydroneopterin Triphosphate

The enzyme which catalyzes the first step in BH4 biosynthesis from dihydro­neopterin triphosphate (NH2TP, cf (A), Fig. 1) has recently been purified to homogeneity from human 1iver. The chemical structure of the product of this conversion has been deduced from its mode of formation, its chemical reactivity, and from trapping experiments to be that of 6-pyruvoyl­tetrahydropterin (PPH4, cf (D). Up to now, however, no direct evidence for this structure has been reported. This is clearly due to the instability of PPH4, a molecule which might exist in several forms, derived, e.g., from cyclization of the side chain with the pterin ring. In view of the importance of this intermediate for the understanding of BH4 biosynthesis, we have attempted to obtain direct experimental evidence for its structure by following the conversion of NH2TP to PPH4 with 1H-NMR