Comparison of Biochemical Activities between Natural 6R- and Unnatural 6S- Isomers of Tetrahydrobiopterin

Abstract

The biochemical activity of natural 6R-form of tetrahydrobiopterin was compared with that of the unnatural 6S-form in terms of the all pterin-requiring monooxygenases, phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase. The unnatural (6S)-isomer showed some comparable in vitro cofactor activities as the natural (6R)-isomer towards the three monooxygenases. How-ever, the natural (6R)-isomer showed a marked in situ or in vivo activities, whereas the unnatural (6S)-isomer had almost no activities. These results suggest that only the natural (6R)-isomer may have in vivo biological activities.