2011 Fiscal Year Final Research Report
Identification and specific makers of abnormal bile acids excreted in inborn errors of bile acid biosynthesis
| Project/Area Number |
21550091
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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 |
Analytical chemistry
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| Research Institution | Nihon University |
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Principal Investigator |
IIDA Takashi 日本大学, 文理学部, 教授 (60060125)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 生体分子 / 異常胆汁酸代謝産物 / LC/ESI-MS/MS / 先天性胆汁酸代謝異常症 / Δ^4-3-オキソ-ステロイド-5β-レダクターゼ欠損症 |
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| Research Abstract |
The synthesis of bile salts from cholesterol is a complex biochemical pathway involving at least 16 enzymes. Most inborn errors of bile acid biosynthesis result in excessive formation of intermediates and/or their metabolites that accumulate in blood and are excreted in part in urine. Early detection is important as oral therapy with bile acids results in improvement. In the past, these intermediates in bile acid biosynthesis have been detected in neonatal blood or urine by screening with FAB-MS followed by detailed characterization using GC-MS. Both methods have proved difficult to automate, and currently most laboratories screen candidate samples using LC-MS/MS. Here, we describe a new, simple and sensitive analytical method for the identification and characterization of 39 conjugated and unconjugated bile acids, including Δ^-3-oxo- and Δ^<4, 6>-3-oxo-bile acids(markers for Δ^4-3-oxo-steroid 5β-reductase deficiency), using liquid chromatography-electrospray ionization tandem mass spectrometry(LC/ESI-MS/MS). In this procedure, a concentrated, desalted urinary sample(diluted with ethanol) is injected directly into the LC-ESI-MS/MS, operated with ESI and in the negative ion mode ; quantification is obtained by selected reaction monitoring(SRM). To evaluate the performance of our new method, we compared it to a validated method using GC-MS, in the analysis of urine from two patients with genetically confirmed Δ^4-3-oxo-steroid-5β-reductase deficiency as well as a third patient with an elevated concentration of abnormal conjugated and unconjugated Δ^4-3-oxo-bile acids. The Δ^4-3-oxo-bile acids concentration recovered in three patients with 5β-reductase deficiency were 48.8, 58.9, and 49.4μmol/mmol Creatinine, respectively by LC/ESI-MS/MS.
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Research Products
(42 results)
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[Journal Article] Identification of S-Acyl Glutathione Conjugates of Bile Acids in Human Bile by means of LC/ESI-MS2011
Author(s)
K. Mitamura, N. Hori, T. Iida, M. Suzuki, T. Shimizu, H. Nittono, K. Takaori, H. Takikawa, A. F. Hofmann, S. Ikegawa
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Journal Title
Steroids
Volume: Vol.76, No.12
Pages: 1609-1614
Peer Reviewed
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[Journal Article] Synthesis of 3-and 21-Monosulfates of [2, 2, 3β, 4, 4-^2H_5]-Tetrahydrocorticosteroiuds in the 5β-Series as Internal Standards for Mass Spectrometry2011
Author(s)
S. Ikegawa, K. Nagase, T. Mabuchi, R. Okihara, M. Hasegawa, T. Minematsu, T. Iida, K. Mitamura
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Journal Title
Steroids
Volume: Vol.76
Pages: 1232-1240
Peer Reviewed
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[Journal Article] Biliary Bile Acids in Birds of the Cotingidae Family : Taurine-Conjugated(24R, 25R)-3α, 7α, 25-Trihydroxy-5β-cholestan-27-oic Acid and Two epimers(25R and 25S) of 3α, 7α-Dihydroxy-5β-cholestan-27-oic Acid2011
Author(s)
L. R. Hagey, T. Iida, S. Ogawa, Y. Adachi, M. Une, K. Mushiake, M. Maekawa, M. Shimada, N. Mano, and A. F. Hofmann
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Journal Title
Steroids
Volume: Vol.76
Pages: 1126-1135
Peer Reviewed
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[Journal Article] Chemical Synthesis of(22E)-3α, 6α, 7α, 12α-Tetrahydroxy-5β-chol-22-en-24-oic Acid and its N-Acylamidated Conjugates with Glycine or Taurine : Presursors of the [22, 23-^3H] Labelled Tracers2010
Author(s)
S. Ogawa, Y. Adachi, G. Kakiyama, M. Shimada, N. Mano, J. Goto, T. Iida
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Journal Title
Chem. Pharm. Bull
Volume: Vol.58, No.8
Pages: 1103-1106
Peer Reviewed
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[Journal Article] MassBank : A Public Repository for Sharing Mass Spectral Data for Life Sciences2010
Author(s)
H. Horai, M. Arita, S. Kanaya, Y. Nihei, T. Ikeda, K. Suwa, Y. Ojima, K. Tanaka, S. Tanaka, K. Aoshima, Y. Oda, Y. Kakazu, M. Kusano, T. Tohge, F. Matsuda, Y. Sawada, H. Nakanishi, K. Ikeda, N. Akimoto, T. Maoka, H. Takahashi, T. Ara, H. Suzuki, D. Shibata, S. Neumann, T. Iida, K. Tanaka, K. Funatsu, F. Matsuura, T. Soga, R. Taguchi, K. Saito, T. Nishioka
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Journal Title
J. Mass Spectrom
Volume: Vol.45
Pages: 703-714
Peer Reviewed
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[Journal Article] Major Biliary Bile Acids of the Medaka(Oryzias latipes): 24R-and 24S-Epimers of 3α, 7α, 12α-Trihydroxy-5β-cholestanoic Acid2010
Author(s)
L. R. Hagey, T. Iida, H. Tamegai, S. Ogawa, M. Une, K. Asahina, K. Mushiake, T. Goto, N. Mano, J. Goto, M. D. Krasowski, A. F. Hofmann
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Journal Title
Zool. Sci
Volume: Vol.27, No.7
Pages: 565-573
Peer Reviewed
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[Journal Article] Potential Corticoid Metabolites : Chemical Synthesis of 3-and 21-Monosulfates and their Double-Conjugates of Tetrahydrocorticosteroids in the 5α-and 5β-Series2010
Author(s)
R. Okihara, K. Mitamura, M. Hasegawa, M. Mori, A. Muto, G. Kakiyama, S. Ogawa, T. Iida, M. Shimada, N. Mano, S. Ikegawa
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Journal Title
Chem. Pharm. Bull
Volume: Vol.58, No.3
Pages: 344-353
Peer Reviewed
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[Journal Article] Oxyfunctionalization of Unactivated C-H Bonds in Triterpenoids with tert-Butylhydroperoxide Catalyzed by Meso-5, 10, 15, 20-tetramesitylporphyrinate Osmium(II) Carbonyl Complex2010
Author(s)
S. Ogawa, Y. Wakatsuki, M. Makino, Y. Fujimoto, K. Yasukawa, T. Kikuchi, M. Ukiya, T. Akihisa, T. Iida
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Journal Title
Chem. Phys. Lipids
Volume: Vol.163
Pages: 165-171
Peer Reviewed
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[Journal Article] A New, Major C_<27> Biliary Bile Acid in the Red-Winged Tinamou(Rhynchotus rufescens :(24R)-1β, 3α, 7α-Trihydroxy-5β-cholestan-27-oic Acid2009
Author(s)
L. R. Hagey, G. Kakiyama, A. Muto, T. Iida, K. Mushiake, T. Goto, N. Mano, J. Goto, G. A. Oliveira, A. F. Hofmann
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Journal Title
J. Lipid Res
Volume: Vol.50
Pages: 651-657
Peer Reviewed
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[Presentation] オオトカゲ胆嚢胆汁成分から新規胆汁酸の単離・同定: Tauro-(24R, 25S)-3α, 7α, 12α, 24-tetrahydroxy-5β-cholestan-27-oic acid2012
Author(s)
小川祥二郎, 飯田隆, 三田村邦子, 池川繁男, 宇根瑞穂, L. R. Hagey, A. F. Hofmann
Organizer
日本薬学会第132年会
Place of Presentation
北海道大学
Year and Date
20120328-31
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