1999 Fiscal Year Final Research Report Summary
Occurrence of a New Tetrahydrobiopterin Synthesizing enzyme in the human being
| Project/Area Number |
10670765
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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 Humanity and Science, Professor, 文理学部, 教授 (50059937)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Tetrahydrobiopterin / Biosynthesis of BH4 / Carbonyl Reductase / Atypical Phenylketonuria / Sepiapterin Reductase |
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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 from 6-pyruvoyl-tetrahydropterin [which is different from sepiapterin reductase (EC 1.1.1.153)] 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). The CR I enzyme converted 6-pyruvoyl-tetrahydropterin to 6-lactoyl-tetrahydropterin, while CR II converted 6-pyruvoyl-tetrahydropterin to 1'-hydroxy-2'-oxopropyl-tetrahydropterin, both reactions occurred only in the presence of NADPH.Neither of the two carbonyl reductases alone was able to catalyze the conversion of 6-pyruvoyl-tetrahydropterin to tetrahydrobiopterin in the presence of NADPH.However when CR I was mixed with CR II in the reaction mixture, 6-pyruvoyl-tetrahydropterin was reduced to tetrahydrobiopterin in the presence of NADPH.Moreover, CR I catalyzed the formation of tetrahydrobiopterin froml'-hydroxy-2'-oxopropyl-tetrahydropterin, while CR II converted 6-lactoyl-tetrahydropterin to tetrahydrobiopterin, both reactions occurred only in thepresence of NADPH.Our results suggest that there are two potential routes for formation of tetrahydrobiopterin from 6-pyruvoyl-tetrahydropterin in the lemon mutant silkworm. In the first route, 1'-hydroxy-2'-oxopropyl-tetrahydropterin is formed from 6-pyruvoyl-tetrahydropterin by CR II and then reduced to tetrahydrobiopterin by CR I, both reactions occurred only in the presence of NADPH.In the other route, 6-pyruvoyl-tetrahydropterin is reduced to 6-lactoyl-tetrahydropterin by CR I, and then converted to tetrahydrobiopterin by CR II, both reactions occurred only in the presence of NADPH.
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