Accumulated BH4 in mouse liver caused by administration of either 6R- or 6SBH4 consisted solely of the 6R-diastereomer: evidence of oxidation to BH2 and enzymic reduction.

Mice were given (i.p.) L-erythro-(6S)-tetrahydrobiopterin (6SBH4) or 6RBH4 and the increase in liver BH4 in both groups was almost the same. The C6-chirality of liver BH4 was determined by HPLC. After administration of 6SBH4, the liver BH4 consisted mainly of 6RBH4 (>95%). These findings show that the exogenous BH4 was oxidized to 7,8BH2 which was then taken up and enzymically reduced back to BH4 in the liver.