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

2014 Fiscal Year Final Research Report

• Project/Area Number: 24550107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Analytical chemistry
• Research Institution: Nihon 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
• 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

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.

Free Research Field

化学