| Project/Area Number |
18591170
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nihon University |
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Principal Investigator |
IINO Teruhiko Nihon University, College of Humanities and Sciences, Professor (50059937)
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| Co-Investigator(Kenkyū-buntansha) |
SHINTAKU Haruo Osaka City University, Graduate School of Medicine, Associate Professor (00206319)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,870,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Tetrahydrobiopterin / Carbonyl reductase / BH4 deficiency / Sepiapterin reductase deficiency / Biosynthesis of tetrahydrobiopterin / AKR family / AKR1B1 / AKR1C3 / セピアプテリン |
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| Research Abstract |
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.
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