| 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)
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| 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.
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