Rebrin I, Bailey S W, Ayling J E
Department of Pharmacology, University of South Alabama, Mobile 36688, USA.
Biochem Biophys Res Commun. 1995 Dec 26;217(3):958-65. doi: 10.1006/bbrc.1995.2863.
The dehydratase activity of the bifunctional protein, 4a-hydroxy-tetrahydropterin 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 increases linearly with time, reaching 31% of the adult value by 17.3 weeks of gestational age. Close correlation was found with the development of dihydropteridine reductase, which increased linearly to 37% of the adult value at 17.3 weeks of gestation. From 8-18 weeks of gestation tetrahydrobiopterin in fetal liver was 0.86 microM (33% of adult value). The ratio of 7-biopterin to 6-biopterin was more than 8-fold higher in fetal than in adult liver during this time. The co-development of 4a-hydroxytetrahydropterin dehydratase with dihydropteridine reductase strongly supports a physiologically significant role for the dehydratase in tetrahydrobiopterin regeneration. In addition, the results have lead to a hypothesis for the transient nature of the hyperphenylalaninemia observed in a variant form of PKU in which levels of 7-biopterin are elevated.
在人类胎儿发育早期，对双功能蛋白4a-羟基四氢蝶呤脱水酶/DCoH的脱水酶活性进行了测定，以确定其是否与苯丙氨酸羟化系统的其他成分同时出现。脱水酶的催化活性早在6.7周时就可检测到，并随时间呈线性增加，到孕17.3周时达到成人值的31%。发现其与二氢蝶啶还原酶的发育密切相关，后者在孕17.3周时线性增加至成人值的37%。在孕8至18周期间，胎儿肝脏中的四氢生物蝶呤为0.86微摩尔（成人值的33%）。在此期间，胎儿肝脏中7-生物蝶呤与6-生物蝶呤的比例比成人肝脏高8倍以上。4a-羟基四氢蝶呤脱水酶与二氢蝶啶还原酶的共同发育有力地支持了脱水酶在四氢生物蝶呤再生中的生理重要作用。此外，这些结果导致了一个关于在一种7-生物蝶呤水平升高的苯丙酮尿症变异形式中观察到的高苯丙氨酸血症短暂性的假说。
