The fate of bilirubin-IXalpha glucuronide in cholestasis and during storage in vitro. Intramolecular rearrangement to positional isomers of glucuronic acid.
1. In aqueous solution above pH7 bilirubin-IXalpha 1-O-acylglucuronide rapidly isomerizes to the non-C-1 glucuronides by sequential migration of the bilirubin acyl group from position 1 to positions 2, 3 and 4 of the sugar moiety. The transformations are enhanced by increasing the pH. Compared with the rates at 37 degrees C the transformations are rather slow at 0 degrees C. Virtually complete inhibition is observed at values below pH6. The isomerization at 25 degrees C and pH 7.4 is not affected by the presence in the solutions of a molar excess of human serum albumin. 2. Isomerization in bile kept at 37 degrees C at pH7.7-7.8 is probably non-enzymic, as the rates of change are similar to those observed under comparable conditions for aqueous solutions of glucuronides of bilirubin-1Xalpha and of azodipyrrole. 3. Analysis without delay of normal biles of man and rats collected at 0 degrees C over a maximum period of 10 min shows that the bilirubin-IXalpha mono- and di-glucuronides consist exclusively of the 1-O-acyl isomers. 4. The mixtures of the four positional isomers of bilirubin-IXalpha glucuronide found in freshly collected biles of man and rats with cholestasis probably originate from initially synthesized 1-O-acylglucuronide by the same mechanism of sequential migration as has been observed in aqueous solutions of conjugated bilirubin-IXalpha.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002779:Cholestasis / Q000201:enzymology / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D008099:Liver / Q000201:enzymology; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
D005965:Glucuronates; D012709:Serum Albumin; D014453:Glucuronosyltransferase; D001663:Bilirubin