1996 Fiscal Year Final Research Report Summary
BIOSYNTHETIC RESEARCH OF FETAL BILE ACID AND ANALYSIS OF CONGENITAL DISORDER OF BILE ACID BIOSYNTHESIS
| Project/Area Number |
07672323
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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 |
Physical pharmacy
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| Research Institution | HEALTH SCIENCES UNIVERSITY OF HOKKAIDO |
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Principal Investigator |
KUROSAWA Takao HEALTH SCIENCE UNIV.OF HOKKAIDO FAC.OF PHARMACEUTICAL SCIENCES,ASSOCIATE PROFESSOR, 薬学部, 助教授 (50103198)
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| Co-Investigator(Kenkyū-buntansha) |
TOHMA Masahiko HEALTH SCIENCES UNIV.OF HOKKAIDO FAC.OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (30001043)
YOSHIMURA Teruki HEALTH SCIENCES UNIV.OF HOKKAIDO FAC.OF PHARMACEUTICAL SCIENCES,ASSISTANT PROFES, 薬学部, 講師 (60220737)
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| Project Period (FY) |
1995 – 1996
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| Keywords | FETAL BILE ACID / STEREOISOMER / C_<27>-BILE ACID / BIOSYNTHERTIC INTERMEDIATE / GAS CHROMATOGRAPHY / beta-OXIDATION / ZELLWEGER SYNDROME / HPLC |
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| Research Abstract |
To clarify the biosynthetic pathway of fetal bile acids and the substrate specificity of beta-oxidation enzymes system were investigated, and the analytic application of the determination of bile acid intermediates in urine with congenital disorder of bile acid biosynthesis was performed to establish a convenient diagnosis for Zellweger syndrome The intermediates of bile acid biosynthesis (C_<27>-bile acids) were synthesized by the nwely developed synthetic method. The stereoisomers of the intermediates and the C_<27>-bile acid analogues containing the precursor for fetal bile acids were also synthesized to make clear the substrate and stereoselectivity of related enzymes(beta-oxidation enzymes). Using the above synthetic standard, the quantitative and simultaneous analytical methods for bile acid intermediates were developed by GC/MS and HPLC.The incubation of synthetic samples with rat liver homogenate was tired and the products were quantitatively determined by the above analytical methods. The results indicated that fetal bile acids (1beta-and 6alpha-hydroxylated cholic acids) are biologically synthesized through the beta-oxidation pathway. The substrate and stereoselectivity of the related enzymes were also investigated and the results showed the substrate specificity conccrning to the numbers of hydroxyl groups and high stereoselectivity for the formation of intermediates. The analytical method were applied to the analysis of bile acids in urine of a patient of Zellweger syndrome. The quantitative analysis clearly showed the deficiency of beta-oxidation system for bile acid biosynthesis. And the C_<27>-precursor of fetal bile acids were also determined.
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