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Interaction of uridine 5'-diphosphoglucuronic acid with microsomal UDP-glucuronosyltransferase in primate liver: the facilitating role of uridine 5'-diphospho-N-acetylglucosamine. 1988

S C Hauser, and B J Ransil, and J C Ziurys, and J L Gollan
Department of Medicine, Harvard Medical School, Boston, MA.

Cytosolic uridine 5'-diphosphoglucuronic acid is the essential cosubstrate for all hepatic microsomal UDP-glucuronosyltransferase-mediated reactions. Uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) has been implicated as an activator of UDP-glucuronosyltransferases in vivo, acting either as an allosteric effector or by enhancing access of uridine 5'-diphosphoglucuronic acid to the enzyme. To delineate the interaction of uridine 5'-diphosphoglucuronic acid with microsomal UDP-glucuronosyltransferase and the facilitating role of UDP-GlcNAc, we analyzed bilirubin UDP-glucuronosyltransferase kinetics in microsomes prepared from monkey liver (Macaca fascicularis). Initial rates of bilirubin glucuronide formation were determined by radiochemical assay over a range of uridine 5'-diphosphoglucuronic acid concentrations (0-60 mM), in native microsomes with or without UDP-GlcNAc, or in detergent (digitonin)-pretreated membranes with UDP-GlcNAc. For native microsomes in the absence of UDP-GlcNAc, fitting the data to each of two mathematical models yielded behavior consistent with a single-site model (Km 2.8 mM). In contrast, in the presence of a physiologic concentration (1 mM) of UDP-GlcNAc, analysis of the data excluded the single-site model and was indicative of a non-interactive, two-site (or process) model, characterized by a high-affinity site (Km 0.14 mM) in addition to the low-affinity site. Following detergent-treatment of microsomal membranes, the data were again most consistent with a single low-affinity site.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014453 Glucuronosyltransferase A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. Glucuronyltransferase,UDP Glucuronosyltransferase,17 beta-Hydroxysteroid UDP-Glucuronosyltransferase,4-Nitrophenol-UDP-Glucuronosyltransferase,7-Hydroxycoumarin UDP Glucuronyltransferase,Androsterone UDP-Glucuronosyltransferase,Bilirubin UDP-Glucuronyltransferase,Estrogen UDP-Glucuronosyltransferase,Estrone Glucuronyltransferase,Glucuronic Transferase,Morphine Glucuronyltransferase,UDP Glucuronyl Transferase,UDP-Glucuronic Acid 3-O-beta-D-Galactosyl-D-Galactose Glucuronosyltransferase,p-Nitrophenyl UDP-Glucuronosyltransferase,17 beta Hydroxysteroid UDP Glucuronosyltransferase,4 Nitrophenol UDP Glucuronosyltransferase,7 Hydroxycoumarin UDP Glucuronyltransferase,Androsterone UDP Glucuronosyltransferase,Bilirubin UDP Glucuronyltransferase,Estrogen UDP Glucuronosyltransferase,Glucuronosyltransferase, UDP,Glucuronyl Transferase, UDP,Glucuronyltransferase, 7-Hydroxycoumarin UDP,Glucuronyltransferase, Estrone,Glucuronyltransferase, Morphine,Transferase, Glucuronic,Transferase, UDP Glucuronyl,UDP Glucuronic Acid 3 O beta D Galactosyl D Galactose Glucuronosyltransferase,UDP Glucuronyltransferase, 7-Hydroxycoumarin,UDP-Glucuronosyltransferase, 17 beta-Hydroxysteroid,UDP-Glucuronosyltransferase, Androsterone,UDP-Glucuronosyltransferase, Estrogen,UDP-Glucuronosyltransferase, p-Nitrophenyl,UDP-Glucuronyltransferase, Bilirubin,p Nitrophenyl UDP Glucuronosyltransferase
D014535 Uridine Diphosphate Glucuronic Acid A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. UDP Glucuronic Acid,UDPGA,Uridine Diphosphoglucuronic Acid,Acid, UDP Glucuronic,Acid, Uridine Diphosphoglucuronic,Diphosphoglucuronic Acid, Uridine,Glucuronic Acid, UDP
D014537 Uridine Diphosphate N-Acetylglucosamine Serves as the biological precursor of insect chitin, of muramic acid in bacterial cell walls, and of sialic acids in mammalian glycoproteins. UDP Acetylglucosamine,UDPGNAc,Uridine Diphospho-N-Acetylglucosamine,Uridine Pyrophosphoacetylglucosamine,Uridine Diphosphate N Acetylglucosamine,Acetylglucosamine, UDP,Diphosphate N-Acetylglucosamine, Uridine,Diphospho-N-Acetylglucosamine, Uridine,N-Acetylglucosamine, Uridine Diphosphate,Pyrophosphoacetylglucosamine, Uridine,Uridine Diphospho N Acetylglucosamine
D014539 Uridine Diphosphate Sugars Nucleotide-sugars such as uridine-diphosphate glucose or UDP-glucose. UDP Sugars,Diphosphate Sugars, Uridine,Sugars, UDP,Sugars, Uridine Diphosphate

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