ACTIVITY OF THE BIFUNCTIONAL PROTEIN 4A-HYDROXY-TETRAHYDROPTERIN DEHYDRATASE DCOH DURING HUMAN FETAL DEVELOPMENT - CORRELATION WITH DIHYDROPTERIDINE REDUCTASE-ACTIVITY AND TETRAHYDROBIOPTERIN LEVELS/

The dehydratase activity of the bifunctional protein, 4a-hydroxy-tetra hydropterin dehydratase/DCoH was measured in liver during early human fetal development to determine whether it appeared in concert with the other components of the phenylalanine hydroxylating system. Catalytic activity of the dehydratase is detectable as early as 6.7 weeks and i ncreases linearly with time, reaching 31% of the adult value by 17.3 w eeks of gestational age. Close correlation was found with the developm ent of dihydropteridine reductase, which increased linearly to 37% of the adult value at 17.3 weeks of gestation. From 8-18 weeks of gestati on tetrahydrobiopterin in fetal liver was 0.86 mu M (33% of adult valu e). The ratio of 7-biopterin to 6-biopterin was more than 8-fold highe r in fetal than in adult liver during this time. The co-development of 4a-hydroxytetrahydropterin dehydratase with dihydropteridine reductas e strongly supports a physiologically significant role for the dehydra tase in tetrahydrobiopterin regeneration, In addition, the results hav e lead to a hypothesis for the transient nature of the hyperphenyl-ala ninemia observed in a variant form of PKU in which levels of 7-biopter in are elevated. (C) 1995 Academic Press, Inc.