Expression analysis of the aldo-keto reductases involved in the novel biosynthetic pathway of tetrahydrobiopterin in human and mouse tissues

四氢生物蝶呤（BH_4）作为芳香氨基酸羟化酶的辅助因子，其缺乏可导致高苯丙氨酸血症（HPA）和神经递质产生减少。以6-pyruvoyl-tetrahydropterin （PPH_4）为原料，采用sepapterin还原酶（SPR）合成BH_4。SPR缺乏的患者没有HPA；然而，SPR基因敲除小鼠表现为HPA。我们报道了与spr无关的PPH_4到BH_4的新型生物合成途径（打捞途径II），其中3a-羟基类固醇脱氢酶2型和醛糖还原酶协同工作。在本研究中，我们对这两种蛋白在人和野生型小鼠中的表达进行了分析。表达分析结果表明，挽救通路II在人肝脏中起作用；但对人脑、小鼠肝脏和大脑均无作用。因此，SPR缺乏症患者可能在无HPA的情况下表现为进行性神经功能恶化，SPR基因敲除小鼠可能表现为HPA和异常运动活动。

Tetrahydrobiopterin (BH_4) acts as a cofactor of the aromatic amino acid hydroxylases, and its deficiency may result in hyperphenylalaninemia (HPA) and decreased production of the neurotransmitters. BH_4 is synthesized by sepiapterin reductase (SPR) from 6-pyruvoyl-tetrahydropterin (PPH_4). A patient with SPR deficiency shows no HPA; however, an SPR knockout mouse exhibits HPA. We have reported on the SPR-unrelated novel biosynthetic pathway from PPH_4 to BH_4 (salvage pathway II). in which 3a-hydroxysteroid dehydrogenase type 2and aldose reductase work in concert. In this study, we performed the expression analysis of both proteins in humans and wild-type mice. The results of expression analysis indicated that salvage pathway II worked in human liver; however, it did not act in human brain or in mouse liver and brain. For this reason, a patient with SPR deficiency may show progressive neurological deterioration without HPA, and SPR knockout mice may exhibit HPA and abnormal locomotion activity.