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• W1522241387 endingPage "16950" @default.
• W1522241387 startingPage "16943" @default.
• W1522241387 abstract "Hepatic biotransformation of bilirubin to the hydrophilic species bilirubin mono- (BMG) and diglucuronide (BDG) by microsomal bilirubin UDP-glucuronosyl-transferase (GT) is a prerequisite for its physiologic excretion into bile. The reaction mechanism of bilirubin-GT and the access of bilirubin and BMG (the intermediate substrate) to the active site of bilirubin-GT are undefined. Highly purified [14C]bilirubin and [3H] BMG were coincubated with rat liver microsomes, and the initial rates of radiolabeled bilirubin glucuronide synthesis were measured. Although these substrates differ markedly in their hydrophilicity, no significant differences were observed in [14C]- and [3H]BDG rates of formation from equimolar [14C]bilirubin and [3H] BMG, in the absence or presence of soluble binding proteins (albumin and hepatic cytosol). In further kinetic studies, [14C]bilirubin and [3H]BMG exhibited mutually competitive inhibition of [3H]- and [14C]BDG synthesis, respectively, and [3H]BMG also inhibited [14C]BMG formation. Finally, unlabeled BMG and BDG inhibited the glucuronidation of [14C]bilirubin, with all three pigments yielding virtual Michaelis-Menten dissociation constants in the 10-20 microM range. These findings indicate that: 1) bilirubin-GT follows Michaelis-Menten kinetics for both bilirubin and BMG glucuronidation over the range of substrate concentrations employed; 2) the findings are consistent with a single active site for the enzymatic synthesis of both BMG and BDG; 3) bilirubin, BMG, and BDG bind competitively to this active site with comparable affinities; and 4) access of both bilirubin and BMG substrates to the enzymatic active site is reduced by soluble binding proteins." @default.
• W1522241387 created "2016-06-24" @default.
• W1522241387 creator A5007506005 @default.
• W1522241387 creator A5008473986 @default.
• W1522241387 creator A5050454700 @default.
• W1522241387 creator A5090687371 @default.
• W1522241387 date "1992-10-01" @default.
• W1522241387 modified "2023-09-27" @default.
• W1522241387 title "Hepatic microsomal bilirubin UDP-glucuronosyltransferase. The kinetics of bilirubin mono- and diglucuronide synthesis." @default.
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• W1522241387 doi "https://doi.org/10.1016/s0021-9258(18)41876-5" @default.
• W1522241387 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1512236" @default.
• W1522241387 hasPublicationYear "1992" @default.
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