2001 Fiscal Year Final Research Report Summary
Relationship of atypical phenylketonuria and a new type of carbonyl reductase which related to synthesize BH4
| Project/Area Number |
12670785
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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, 文理学部, 教授 (50059937)
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| Co-Investigator(Kenkyū-buntansha) |
SHINTAKU Haruo Osaka City University, School of medicine, Associate Professor, 医学部, 助教授 (00206319)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Tetrahydrobiopterin / Carbonyl reductase / Biosynthesis of BH4 / BH4 deficiency |
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| Research Abstract |
Tetrahydrobiopterin plays an important role in the biosynthesis of certain neurotransmitters. Using DEAE-Sepharose FF column chromatography, we separated the enzyme that synthesizes tetrahydrobiopterin(BH4) from 6- pyruvoyl-tetrahydropterin(PPH4), which is different from sepiapterin reductase, in the lemon mutant of the silkworm, Bombyx mori , into two fractions, which were named carbonyl reductase I ( CR I ) and carbonyl reductase II ( CR II ). When CR I was mixed with CR II in the reaction mixture, PPH4 was reduced to BH4 in the presence of NADPH.
Furthermore, we examined the formation of BH4 from PPH4 by several human carbonyl reductases which belong to the aldo-keto reductase ( AKR1) family members. In these experiments, AKR1A1, AKR1B1, AKR1C1, AKR1C2, and AKR1C4 converted PPH4 to 1'-oxo-2'-hydroxypropyl-tetrahydropterin, while AKR1C3 converted PPH4 to 1'-hydroxy-2'-oxopropyl-tetrahydropterin, both reactions occurred only in the presence of NADPH. Neither of these carbonyl reductases alone was able to catalyze the conversion of PPH4 to BH4 in the presence of NADPH.
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