Skip to main content
NCBI home page
Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 1997 Jul;77(1):F52–F56. doi: 10.1136/fn.77.1.f52

Developmental pattern of 3-oxo-Δ4 bile acids in neonatal bile acid metabolism

T Inoue, A Kimura, K Aoki, M Tohma, H Kato
PMCID: PMC1720670  PMID: 9279184

Abstract

AIMS—To investigate whether a fetal pathway of bile acid synthesis persists in neonates and infants.
METHODS—3-oxo-Δ4 bile acids were determined qualitatively and quantitatively in the urine, meconium, and faeces of healthy neonates and infants, using gas chromatography-mass spectrometry.
RESULTS—The mean percentage of 3-oxo-Δ4 bile acids in total bile acids in urine at birth was significantly higher than that at 3 or 7 days, and at 1 or 3 months of age. The concentration of this component in meconium was significantly higher than that in faeces at 7 days and at 1 or 3 months of age.
CONCLUSIONS—The presence of large amounts of urinary 3-oxo-Δ4 bile acids may indicate immaturity in the activity of hepatic 3-oxo-Δ4-steroid 5β-reductase in the first week of postnatal life. Large amounts of this component in meconium may be due to the ingestion of amniotic fluid by the fetus during pregnancy.

 Keywords: ketonic bile acid; 3-oxo-Δ4 bile acid; 3-oxo-Δ4-steroid 5β-reductase; meconium; gas chromatography-mass spectrometry

Full Text

The Full Text of this article is available as a PDF (152.2 KB).

Figure 1  .

Figure 1  

Open in a new tab

Selected ion GC-MS chromatogram of the methyl ester-trimethylsilyl ether derivatives of a mixture of reference bile acids:1 Nor-CDCA; 2 LCA; 3 DCA; 4 Δ5-3β-ol; 5 CDCA; 6 UDCA; 7 HCA; 8 CA; 9 Δ1-3-one; 10 3-oxo-Δ4 bile acids; 11 CA-1β-ol; 12 CDCA-1β-ol.

Figure 2  .

Figure 2  

Open in a new tab

Percentage of unconjugated bile acids and of taurine, glycine, and sulphate conjugated bile acids in the urine of neonates in the first week after birth.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clayton P. T., Patel E., Lawson A. M., Carruthers R. A., Tanner M. S., Strandvik B., Egestad B., Sjövall J. 3-Oxo-delta 4 bile acids in liver disease. Lancet. 1988 Jun 4;1(8597):1283–1284. doi: 10.1016/s0140-6736(88)92104-6. [DOI] [PubMed] [Google Scholar]
  2. Coleman J. P., White W. B., Egestad B., Sjövall J., Hylemon P. B. Biosynthesis of a novel bile acid nucleotide and mechanism of 7 alpha-dehydroxylation by an intestinal Eubacterium species. J Biol Chem. 1987 Apr 5;262(10):4701–4707. [PubMed] [Google Scholar]
  3. Colombo C., Roda A., Roda E., Buscaglia M., dell'Agnola C. A., Filippetti P., Ronchi M., Sereni F. Correlation between fetal and maternal serum bile acid concentrations. Pediatr Res. 1985 Feb;19(2):227–231. doi: 10.1203/00006450-198502000-00018. [DOI] [PubMed] [Google Scholar]
  4. Kimura A., Mahara R., Tohma M., Ushijima K., Yuge K., Ono E., Yamashita F. Unusual 1 beta-hydroxylated bile acids in children with a paucity in interlobular bile ducts. Clin Chim Acta. 1989 Nov;185(2):215–217. doi: 10.1016/0009-8981(89)90048-x. [DOI] [PubMed] [Google Scholar]
  5. Kimura A., Yamakawa R., Ushijima K., Fujisawa T., Kuriya N., Kato H., Inokuchi T., Mahara R., Kurosawa T., Tohma M. Fetal bile acid metabolism during infancy: analysis of 1 beta-hydroxylated bile acids in urine, meconium and feces. Hepatology. 1994 Oct;20(4 Pt 1):819–824. doi: 10.1002/hep.1840200408. [DOI] [PubMed] [Google Scholar]
  6. Leppik R. A. Improved synthesis of 3-keto, 4-ene-3-keto, and 4,6-diene-3-keto bile acids. Steroids. 1983 Apr;41(4):475–484. doi: 10.1016/0039-128x(83)90087-9. [DOI] [PubMed] [Google Scholar]
  7. Nakagawa M., Setchell K. D. Bile acid metabolism in early life: studies of amniotic fluid. J Lipid Res. 1990 Jun;31(6):1089–1098. [PubMed] [Google Scholar]
  8. Rotimi V. O., Duerden B. I. The development of the bacterial flora in normal neonates. J Med Microbiol. 1981 Feb;14(1):51–62. doi: 10.1099/00222615-14-1-51. [DOI] [PubMed] [Google Scholar]
  9. Schölmerich J., Becher M. S., Schmidt K., Schubert R., Kremer B., Feldhaus S., Gerok W. Influence of hydroxylation and conjugation of bile salts on their membrane-damaging properties--studies on isolated hepatocytes and lipid membrane vesicles. Hepatology. 1984 Jul-Aug;4(4):661–666. doi: 10.1002/hep.1840040416. [DOI] [PubMed] [Google Scholar]
  10. Setchell K. D., Suchy F. J., Welsh M. B., Zimmer-Nechemias L., Heubi J., Balistreri W. F. Delta 4-3-oxosteroid 5 beta-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis. J Clin Invest. 1988 Dec;82(6):2148–2157. doi: 10.1172/JCI113837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shoda J., Tanaka N., Osuga T., Matsuura K., Miyazaki H. Altered bile acid metabolism in liver disease: concurrent occurrence of C-1 and C-6 hydroxylated bile acid metabolites and their preferential excretion into urine. J Lipid Res. 1990 Feb;31(2):249–259. [PubMed] [Google Scholar]
  12. Strandvik B., Wahlén E., Wikström S. A. The urinary bile acid excretion in healthy premature and full-term infants during the neonatal period. Scand J Clin Lab Invest. 1994 Feb;54(1):1–10. doi: 10.3109/00365519409086503. [DOI] [PubMed] [Google Scholar]
  13. Suchy F. J., Balistreri W. F., Heubi J. E., Searcy J. E., Levin R. S. Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants. Gastroenterology. 1981 May;80(5 Pt 1):1037–1041. [PubMed] [Google Scholar]
  14. Tohma M., Mahara R., Takeshita H., Kurosawa T., Ikegawa S. Synthesis of the 1 beta-hydroxylated bile acids, unusual bile acids in human biological fluids. Chem Pharm Bull (Tokyo) 1986 Jul;34(7):2890–2899. doi: 10.1248/cpb.34.2890. [DOI] [PubMed] [Google Scholar]
  15. Tohma M., Takeshita H., Mahara R., Kurosawa T., Makino I. Determination of 3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid and related bile acids in human serum by gas chromatography-mass spectrometry. J Chromatogr. 1987 Oct 9;421(1):9–19. doi: 10.1016/0378-4347(87)80374-2. [DOI] [PubMed] [Google Scholar]
  16. Wahlén E., Egestad B., Strandvik B., Sjoóvall J. Ketonic bile acids in urine of infants during the neonatal period. J Lipid Res. 1989 Dec;30(12):1847–1857. [PubMed] [Google Scholar]
  17. Wahlén E., Strandvik B. Effects of different formula feeds on the developmental pattern of urinary bile acid excretion in infants. J Pediatr Gastroenterol Nutr. 1994 Jan;18(1):9–19. doi: 10.1097/00005176-199401000-00002. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood Fetal and Neonatal Edition are provided here courtesy of BMJ Publishing Group

RESOURCES