Changes in the Composition of Bilirubin‐IX Isomers During Human Prenatal Development

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Abstract
We analyzed the isomeric composition of bilirubin-IX in human fetal bile using HPLC. The approximate ratio of the bilirubin-IX isomers obtained from the fetal bile at 20 weeks of gestation was IXα, 6%; IXβ, 87%; IXγ, 0.5%; and IXδ, 6%. From 15 to 22 weeks, bilirubin-IXβ was predominant and bilirubin-IXδ and bilirubin-IXα were also present in the bile as minor components. By 28 weeks, bilirubin-IXα constituted about 50% of the total bilirubin. There was a general correlation between fetal age and the proportion of bilirubin-IXβ to bilirubin-IXβ in the bile and the small intestinal contents of fetuses. As development proceeded from mid-gestation to near term, the isomeric composition dramatically changed, with a decrease in the IXβ isomer and a subsequent increment of the IXα isomer. In contrast, the IXβ isomer changes little. Recently, we identified four forms of biliverdin reductase including two biliverdin-IXα reductases and two biliverdin-IXβ reductases in human liver cytosolic fractions [Yamaguchi, T., Komoda, Y. & Nakajima, H. (1994) J. Biol. Chem. 269, 24343–24348]. The proportion of the total activity of biliverdin-IXβ reductases to that of biliverdin-IXα reductases was considerably higher in the fetal, than in the adult liver.

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