DEVELOPMENTAL-CHANGES OF TETRAHYDROBIOPTERIN IN RAT AND HUMAN ERYTHROCYTES

In the present study, we investigated the developmental changes of: (1 ) plasma and erythrocyte tetrahydrobiopterin (BH4); (2) erythrocyte GT P cyclohydrolase (the rate-limiting enzyme of BH4 biosynthesis); (3) t he permeability of erythrocyte membrane to BH4; and (4) plasma phenyla lanine, both in healthy human subjects and Wistar rats. In vitro exper iments demonstrated passive transport of BH4 into erythrocytes. In hum ans, BH4 levels as well as the other parameters were fairly consistent across all age groups. In contrast, Wistar rats showed significant de velopmental changes in erythrocyte BH4, which were not simply correlat ed to either GTP cyclohydrolase, permeability to BH4, or plasma phenyl alanine levels. This may suggest the existence of other factors regula ting the homeostasis of BH4, such as BH4-binding capacity in plasma an d/or erythrocytes. These species/age differences in erythrocyte charac teristics may influence the pharmacological behavior and clinical effi cacy of BH4 in humans and experimental animals.