Microsomal UDP-glucuronyltransferase-catalyzed bilirubin diglucuronide formation in human liver |
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| Authors: | W H Peters P L Jansen |
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| Affiliation: | 1. Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China;2. Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China;3. GI Biopharma Inc., Westfield, NJ, 07090, USA;1. Gut Microbes and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich, United Kingdom;2. Department of Biology, University of York, York, United Kingdom;3. Division of Structural Biology, University of Oxford, Headington, Oxford, United Kingdom;4. School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom;5. Departamento de Química Orgánica, Universidad de Sevilla, Sevilla, Spain;6. Instituto de Investigaciones Químicas (CSIC-US), Sevilla, Spain;1. Department of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria;2. Division of Translational Cell Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria;3. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 17177 Stockholm, Sweden;4. Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland;5. Department of Orthopedic Surgery, Hospital Wels-Grieskirchen, 4600 Wels, Austria;1. Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic;2. Institute for Biophysics, Johannes Kepler University Linz, A-4040 Linz, Austria;3. Gottfried Schatz Research Center, Medical University of Graz, A-8010 Graz, Austria;4. College of Biomedical Sciences, Larkin University, Miami, FL 33169, United States;1. Clinic for Poultry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany;2. Department of Medicine, University of Veterinary Science, Yezin, Myanmar |
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| Abstract: | Human liver microsomal bilirubin UDP-glucuronyltransferase catalyzes formation of bilirubin mono- and diglucuronide. KmUDPGA and Vmax of the enzyme are 0.6 mM and 1.69 nmol/mg protein X min. In vitro, bilirubin readily dissolves in the microsomal lipid phase. Taking this into account a Kmbilirubin of 60.6 microM was found, which is much higher than the in vivo microsomal UCB concentration of human liver (2.9-11.4 microM). The total capacity of human liver to form bilirubin mono- and diglucuronide in vitro exceeds the in vivo mono- and diglucuronide production rates by a factor 8 to 10. Radiation-inactivation studies reveal that human liver microsomal bilirubin UDP-glucuronyltransferase is a tetrameric enzyme with a molecular mass of 209 000 +/- 20 000 Da. The complete tetrameric enzyme catalyzes both glucuronidation steps, formation of bilirubin monoglucuronide and conversion of mono- to diglucuronide. In its monomeric form, the enzyme with molecular mass of 55 000 +/- 1 500 Da catalyzes only the first step of bilirubin glucuronidation, the formation of bilirubin monoglucuronide. |
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