Journal
JOURNAL OF BIOCHEMISTRY
Volume 146, Issue 1, Pages 51-60Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvp042
Keywords
AKR1B1; AKR1C3; Aldo-keto reductase; BH4 deficiency; SPR deficiency
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [18591170]
- Nihon University Research
- Grants-in-Aid for Scientific Research [18591170] Funding Source: KAKEN
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Tetrahydrobiopterin (BH4) acts as a cofactor of the aromatic amino-acid hydroxylases, and its deficiency may result in hyperphenylalaninemia (HPA) and decreased production of the neurotransmitters. BH4 is synthesized by sepiapterin reductase (SPR) from 6-pyruvoyl-tetrahydropterin (PPH4). 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 PPH4 to BH4 (salvage pathway II) in which 3 alpha-hydroxysteroid dehydrogenase type 2 and 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.
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