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  • 标题:Studies on the Unusual 1β-Hydroxylated Bile Acid Biosynthesis in Infants
  • 本地全文:下载
  • 作者:Yukihiro Nomura ; Hiroyuki Murata ; Hiroaki Sasai
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2018
  • 卷号:41
  • 期号:4
  • 页码:597-603
  • DOI:10.1248/bpb.b17-00986
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Unusual bile acids (1β-hydroxylated bile acids), particularly 1β-hydroxyl-cholic acid (CA-1β-ol) and 1β-hydroxyl-chenodeoxycholic acid (CDCA-1β-ol), have been detected in the urine of infants. These acids are conjugated with amino acids, such as taurine, and are then excreted mainly via the urine. CA-1β-ol and CDCA-1β-ol are the predominant bile acids during infancy and are present in relatively large amounts in the urine. However, the biosynthetic pathway of 1β-hydroxylated bile acids in infants remains unclear. To investigate the biosynthetic pathway of 1β-hydroxylated bile acids during infancy, we performed a metabolic reaction using infant hepatocytes at 3 months after delivery. Glyco- and tauro-CA-1β-ol were identified by LC/tandem mass spectrometry (MS/MS) analysis of the extracted culture medium incubated with cholic acids (CAs). Further, we identified that ketoconazole suppressed CA 1β-hydroxylation and that the CYP3A subfamily was the primary group of enzymes responsible for CA-1β-ol formation. The present study provides new information about the biosynthetic pathway of 1β-hydroxylated bile acids during infancy.

  • 关键词:1β-hydroxylated bile acid;LC/tandem mass spectrometry (MS/MS);CYP3A
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