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Studies on the Unusual 1ß-Hydroxylated Bile Acid Biosynthesis in Infants.
Nomura, Yukihiro; Murata, Hiroyuki; Sasai, Hiroaki; Kimura, Akihiko; Kurosawa, Takao; Sasaki, Takahiro; Murai, Tsuyoshi.
Affiliation
  • Nomura Y; Drug Metabolism and Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc.
  • Murata H; Drug Metabolism and Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc.
  • Sasai H; Drug Metabolism and Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc.
  • Kimura A; Department of Pediatrics and Child Health, Kurume University School of Medicine.
  • Kurosawa T; School of Pharmaceutical Sciences, Health Sciences University of Hokkaido.
  • Sasaki T; School of Pharmaceutical Sciences, Health Sciences University of Hokkaido.
  • Murai T; School of Pharmaceutical Sciences, Health Sciences University of Hokkaido.
Biol Pharm Bull ; 41(4): 597-603, 2018.
Article in En | MEDLINE | ID: mdl-29607932
Unusual bile acids (1ß-hydroxylated bile acids), particularly 1ß-hydroxyl-cholic acid (CA-1ß-ol) and 1ß-hydroxyl-chenodeoxycholic acid (CDCA-1ß-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-1ß-ol and CDCA-1ß-ol are the predominant bile acids during infancy and are present in relatively large amounts in the urine. However, the biosynthetic pathway of 1ß-hydroxylated bile acids in infants remains unclear. To investigate the biosynthetic pathway of 1ß-hydroxylated bile acids during infancy, we performed a metabolic reaction using infant hepatocytes at 3 months after delivery. Glyco- and tauro-CA-1ß-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 1ß-hydroxylation and that the CYP3A subfamily was the primary group of enzymes responsible for CA-1ß-ol formation. The present study provides new information about the biosynthetic pathway of 1ß-hydroxylated bile acids during infancy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cholic Acids / Hepatocytes Limits: Adult / Humans / Infant Language: En Journal: Biol Pharm Bull Journal subject: BIOQUIMICA / FARMACOLOGIA Year: 2018 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cholic Acids / Hepatocytes Limits: Adult / Humans / Infant Language: En Journal: Biol Pharm Bull Journal subject: BIOQUIMICA / FARMACOLOGIA Year: 2018 Type: Article