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Bilirubin Diglucuronide Synthesis by a UDP-Glucuronic Acid-Dependent Enzyme System in Rat Liver Microsomes
Norbert Blanckaert, John Gollan and Rudi Schmid
Proceedings of the National Academy of Sciences of the United States of America
Vol. 76, No. 4 (Apr., 1979), pp. 2037-2041
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/69651
Page Count: 5
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Incubation of rat liver homogenate or microsomal preparations with bilirubin or bilirubin monoglucuronide with (BMG) resulted in formation of bilirubin diglucuronide (BDG). Both synthesis of BMG and its conversion to BDG were critically dependent on the presence of UDP-glucuronic acid. Pretreatment of the animals with phenobarbital stimulated both reactions. When 33 μ M bilirubin was incubated with microsomal preparations from phenobarbital-treated rats, 80-90% of the substrate was converted to bilirubin glucuronides; the reaction products consisted of almost equal amounts of BMG and BDG. When phenobarbital pretreatment was omitted or when the substrate concentration was increased to 164 μ M bilirubin, proportionally more BMG and less BDG were formed. Homogenate and microsomes from homozygous Gunn rats neither synthesized BMG nor converted BMG to BDG. These findings in vitro suggest an explanation for the observations in vivo that, in conditions of excess bilirubin load or of genetically decreased bilirubin UDP glucuronosyltransferase (EC 18.104.22.168) activity, proportionally more BMG and less BDG are excreted in bile.
Proceedings of the National Academy of Sciences of the United States of America © 1979 National Academy of Sciences