| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
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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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