Origin of mammalian biliprotein and rearrangement of bilirubin glucuronides in vivo in the rat.
In hepatobiliary disease bilirubin becomes bound covalently to serum albumin, producing a nondissociable bile pigment-protein complex (biliprotein). To elucidate the mechanism of biliprotein formation we studied the bile pigment composition of blood from animals with experimental cholestasis and carried out comparative studies on the rate of biliprotein formation in vivo and in vitro during incubation of bilirubin glucuronides with albumin. Bile duct ligation in the rat and guinea pig led to rapid accumulation in the circulation of bilirubin, heterogeneous bilirubin esters of glucuronic acid, and a biliprotein that migrated along with albumin on high performance liquid chromatography. When the obstruction was removed, biliprotein remained longer in the circulation than did the other bile pigment species. Biliprotein and heterogeneous bilirubin esters of glucuronic acid were not formed in bile duct-ligated homozygous Gunn rats but they were formed when bilirubin glucuronides were incubated with Sprague-Dawley rat serum or human serum albumin at 37 degrees C in vitro. Bilirubin glucuronide rearrangement in vitro was accompanied by nonenzymic hydrolysis. We conclude that the formation of biliprotein in vivo is probably nonenzymic and suggest that mammalian biliprotein is formed by acyl migration of bilirubin from a bilirubin-glucuronic acid ester to a nucleophilic site on albumin.
D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D001654:Bile Pigments / Q000097:blood; D001663:Bilirubin / Q000031:analogs & derivatives* / Q000097:blood*; D002779:Cholestasis / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000097:blood*
D001654:Bile Pigments; D012709:Serum Albumin; C016266:bilirubin glucuronate; D001663:Bilirubin