Curtius H C, Adler C, Rebrin I, Heizmann C, Ghisla S
Department of Pediatrics, University of Zurich, Switzerland.
Biochem Biophys Res Commun. 1990 Nov 15;172(3):1060-6. doi: 10.1016/0006-291x(90)91554-6.
Previously we described a new form of human hyperphenylalaninemia characterized by the formation of 7-substituted pterins. We present evidence strongly suggesting that the 7-substituted pterins are formed by rearrangement of 6-substituted pterins. This rearrangement occurs during the phenylalanine hydroxylase reaction cycle which normally involves the enzymes phenylalanine hydroxylase, pterin-4a-OH-dehydratase, and q-dihydropterin reductase, specifically in the absence of dehydratase activity. We conclude that formation of 7-substituted pterins in humans is a consequence of an absence of dehydratase activity, which might result from a genetic defect. A chemical mechanism for this rearrangement is presented. Our results also suggest that tetrahydroneopterin can be a cofactor for the phenylalanine hydroxylase system in vivo.
此前我们描述了一种以7-取代蝶呤形成为特征的新型人类高苯丙氨酸血症。我们提供的证据有力地表明，7-取代蝶呤是由6-取代蝶呤重排形成的。这种重排发生在苯丙氨酸羟化酶反应循环中，该循环通常涉及苯丙氨酸羟化酶、蝶呤-4a-OH-脱水酶和q-二氢蝶呤还原酶，特别是在缺乏脱水酶活性的情况下。我们得出结论，人类中7-取代蝶呤的形成是脱水酶活性缺乏的结果，这可能是由遗传缺陷导致的。本文提出了这种重排的化学机制。我们的结果还表明，四氢新蝶呤在体内可能是苯丙氨酸羟化酶系统的一种辅助因子。
