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Metabolome analysis of abnormal bile acids as specific biomarkers in the inborn error of cholesterol biosynthesis (SLOS)

Research Project

Project/Area Number 24550107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Analytical chemistry
Research InstitutionNihon University

Principal Investigator

IIDA Takashi  日本大学, 文理学部, 教授 (60060125)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords生体分子 / 先天性コレステロール代謝異常症 / コレステロール異常代謝産物 / LC/ESI-MS/MS / スミス‐レムリ‐オピッツ症候群(SLOS) / 7-デヒドロコレステロール レダクターゼ欠損症 / SLOS疾患 / LC-MS/MS / 異常胆汁酸 / MassBank / SLOS症候群 / Mass Bank
Outline of Final Research Achievements

The synthesis of bile acids from cholesterol is a complex biochemical pathway involving at least 16 enzymes. Inborn errors of cholesterol biosynthesis in Smith-Lemli-Opitz Syndrome (SLOS: 7-dehydrocholesterol reductase deficiency, Dhcr7) result in excessive formation of abnormal intermediates of 4α- and 4β-hydroxy-7-dehydrocholesterols (as the unconjugated and conjugated forms) and/or their metabolites that accumulate in blood and are excreted in part in urine. In the past, these intermediates in cholesterol 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 identification and chracterization of 4α- and 4β-dehydrocholesterols (as biomarkers for SLOS), using LC/ESI-MS/MS.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 1 results) Presentation (7 results)

  • [Journal Article] Origin of myofiblasts in the fibrotic liver in mice2014

    • Author(s)
      K.Iwaisako, C.Jiang, M.Zhang, M.Cong, T.J.Moore-Morris, T.J.Park, X.Liu, J.Xu, P.Wang, Y-H.Paik, F.Meng, M.Asagiri, L.A.Murray, A.F.Hofmann, T.Iida, C.K.Glass, D.A.Brenner, T.Kisseleva
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 111 Issue: 32

    • DOI

      10.1073/pnas.1400062111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved chemical synthesis, X-ray crystallographic analysis, and NMR characterization of (22R)-/(22S)-hydroxy epimers of bile acids2014

    • Author(s)
      K.Omura, A.Ohsaki, B.Zhou, M.Kushida, T.Mitsuma, A.Kobayashi, L.R.Hagey, A.F.Hofmann, T.Iida
    • Journal Title

      Lipids

      Volume: 49 Pages: 1169-1180

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-methyltaurine N-acyl amidated bile acids and deoxycholic acid in the bile of angelfish (Pomacanthidae): a novel bile acid profile in Perciform fish2014

    • Author(s)
      Okihara, R.S.N., Saito, T., Ogata, H., Ohsaki, A., Iida, T., Asahina, K., Mitamura, K., Ikegawa, S., Hofmann, A.E., Hagey, L.R.
    • Journal Title

      Steroids

      Volume: 80 Pages: 15-23

    • DOI

      10.1016/j.steroids.2013.11.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tandem Mass Spectrometric Characterization of Bile Acid and Steroid Conjugates Based on Low-Energy Collision-Induced Dissociation.2014

    • Author(s)
      M.Maekawa, M.Shimada, T.Iida, J.Goto, N.Mano
    • Journal Title

      Steroids

      Volume: 80 Pages: 80-91

    • DOI

      10.1016/j.steroids.2013.11.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis and NMR Characterization of C-24 Epimeric Pairs of 24-Alkyl Oxysterols2013

    • Author(s)
      S.Ogawa, H.Kawamoto, T.mitsuma, H.Fujimori, T.higashi, T.Iida
    • Journal Title

      Lipids

      Volume: 48 Issue: 2 Pages: 197-207

    • DOI

      10.1007/s11745-012-3739-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] LC/ESI-MS/MS Analysis of Urinary 3β-Sulfo-7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its Amidates: New Biomarkers for the Detection of Niemann-Pick Type C Disease.2013

    • Author(s)
      M.Maekawa, Y.Misawa, A.Sotoura, H.Yamaguchi, M.Togawa, K.Ohno, H.Nittono, G.Kakiyama, T.Iida, A.F.Hofmann, J.Goto, M.Shimada, N.Mano
    • Journal Title

      Steroids

      Volume: 78 Issue: 10 Pages: 967-972

    • DOI

      10.1016/j.steroids.2013.05.017

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] An Efficient Synthesis of 4β-Hydroxy-7-dehydrocholesterol, Biomarkers for Patients with and Animal Models of the Smith-Lemli-Opitz Syndrome.2013

    • Author(s)
      H.Kawamoto, Y.Ohmori, M.Maekawa, M.Shimada, N.Mano, T.Iida
    • Journal Title

      Chemistry and Physics of Lipids

      Volume: 73-78 Pages: 175-176

    • DOI

      10.1016/j.chemphyslip.2013.07.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 3-Sulfates of S-Acyl Glutathione Conjugated Bile Acids and their Biotransformation by a Rat Liver Cytosolic Fraction.2012

    • Author(s)
      K.Mitamura, N.Hori, S.Mino, T.Iida, A.F.Hofmann, S.Ikegawa
    • Journal Title

      Chem. Phys. Lipids

      Volume: 165 Pages: 261-269

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of Δ4-3-Oxo-steroid 5β-Reductase Deficiency by LC-ESI-MS/MS Measurement of Urinary Bile Acids.2012

    • Author(s)
      A.Muto, H.Takei, A.Unnno, T.Murai, T.Kurosawa, S.Ogawa, T.Iida, S.Ikegawa, J.Mori, A.Ohtake, T.Hoshitra, T.Muzuochi, A.,KImura, A.F.Hofmann, L.R.Hagey, H.Nittono
    • Journal Title

      J. Chromagogr. B

      Volume: 900 Pages: 24-31

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Multiply Deuterated 3- and 21-Monmosulfates of Allo-Tetrahydrocorticosteroids as Internal Standards for Mass Spectrometry2012

    • Author(s)
      K.Mitamura, T.Mabuchi, K.Nagae, M.Nakajima, R.Matsumoto, S.Fujioka, K.Sato, R.Sato, T.Iida, S.Ogawa, A.F.Hofmann, S.Ikegawa
    • Journal Title

      Steroids

      Volume: 77 Pages: 1423-1437

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Novel Varanic Acid Epimer-(24R,25S)-3α,7α,12α,24-Tetrahydroxy-5β-cholestan-27-oic Acid-is a Major Biliary Bile Acid in Two Varanid Lizards and the Gila Monster2012

    • Author(s)
      L.R.Hagey, S.Ogawa, N.Kato, R.Satoh, M.Une, K.Mitamura, S.Ikegawa, A.F.Hofmann, T.Iida
    • Journal Title

      Steroids

      Volume: 77 Pages: 1510-1521

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis and NMR Characterization of C-24 Epimeric Pairs of 24-Alkyl Oxysterols2012

    • Author(s)
      S.Ogawa, H.Kawamoto, T.Mitsuma, H.Fujimori, T.Higashi, T.Iida
    • Journal Title

      Lipids

      Volume: 48 Pages: 197-207

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Novel 2β-Hydroxylated bile acids from the gallbladder bile of arapaima (Arapaima gigas)2014

    • Author(s)
      Takashi Iida, et al.
    • Organizer
      XXIII International Bile Acid Meeting (Falk Symposium 194)
    • Place of Presentation
      Freiburg, Germany
    • Year and Date
      2014-10-08 – 2014-10-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chemical synthesis of 11α-hydroxy-derivatives of lithocholic acid chenodeoxycholic acid as potential new natural bile acids2014

    • Author(s)
      Kaoru Omura, et al.
    • Organizer
      XXIII International Bile Acid Meeting (Falk Symposium 194)
    • Place of Presentation
      Freiburg, Germany
    • Year and Date
      2014-10-08 – 2014-10-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Efficient synthesis and anti-inflammatory properties of benzothiazole derivatives of bile acids2014

    • Author(s)
      Naoya Nakane, et al.
    • Organizer
      XXIII International Bile Acid Meeting (Falk Symposium 194)
    • Place of Presentation
      Freiburg, Germany
    • Year and Date
      2014-10-08 – 2014-10-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Solvent-free synthesis of bile acid derivatives having a thiazole group in the side-chain by the combined use of activated carbon/silica and microwave2014

    • Author(s)
      Ryou Sakiyama, et al.
    • Organizer
      The 134th Annual Meeting of the Pharmaceutical Society of Japan
    • Place of Presentation
      Kumamoto City General Gymnasium (Japan)
    • Related Report
      2013 Research-status Report
  • [Presentation] Isolation and structural determination of a novel bile acid taurine conjugate from the bile of Pirarucu(Arapaima gigas)2014

    • Author(s)
      Tetsuya Saito, et al.
    • Organizer
      The 134th Annual Meeting of the Pharmaceutical Society of Japan
    • Place of Presentation
      Kumamoto City General Gymnasium (Japan)
    • Related Report
      2013 Research-status Report
  • [Presentation] Chemical Synthesis of 7α,12α-Dihydroxy-cholest-4-en-3-one and its 12-Deoxy Analogue : Key Intermediates In the Biosynthesis of Bile Acids from Cholesterol2012

    • Author(s)
      Kaoru Omura
    • Organizer
      Falk Symposium 184 XXII International Bile Acid Meeting
    • Place of Presentation
      Wien (Austria)
    • Related Report
      2012 Research-status Report
  • [Presentation] A novel, major epimaer of varanic acid from the bile of monitor lizards: Taurine-conjugated (24R,25S)-3α,7α,12α,24-tetrahydroxy-5β-cholestan-27-oic acid2012

    • Author(s)
      Narimi Kato
    • Organizer
      Falk Symposium 184 XXII International Bile Acid Meeting
    • Place of Presentation
      Wien (Austria)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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