Developmental Changes of Tetrahydrobiopterin in Rat and Human Erythrocytes.

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In the present study, we investigated the developmental changes of:(1) plasma and erythrocyte tetrahydrobiopterin (BH4);(2) erythrocyte GTP cyclohydrolase (the rate-limiting enzyme of BH4 biosynthesis);(3) the permeability of erythrocyte membrane to BH4; and (4) plasma phenylalanine, both in healthy human subjects and Wistar rats. <I>In vitro</I> experiments demonstrated passive transport of BH4 into erythrocytes. In humans, BH4 levels as well as the other parameters were fairly consistent across all age groups. In contrast, Wistar rats showed significant developmental changes in erythrocyte BH4, which were not simply correlated to either GTP cyclohydrolase, permeability to BH4, or plasma phenylalanine levels. This may suggest the existence of other factors regulating the homeostasis of BH4, such as BH4-binding capacity in plasma and/or erythrocytes. These species/age differences in erythrocyte characteristics may influence the pharmacological behavior and clinical efficacy of BH4 in humans and experimental animals.
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