Evidence for glucuronide (small molecule) sorting by human hepatic endoplasmic reticulum.
The entry of substrates into, and the export of glururonides from, the lumen of hepatic endoplasmic reticulum (ER) in vitro (sealed microsomes) has been measured using radioactivity-labelled materials and a rapid filtration assay. Analysis of liver microsomes from a jaundiced patient showed the accumulation of bilirubin glucuronides within the lumen of the ER. Further analysis of these hepatic microsomes revealed that newly synthesized 1-naphthol glucuronide could exit from the microsomes whereas bilirubin glucuronide was accumulated within the microsomes. These results suggest the existence of mechanisms for the sorting of small molecules, destined for export through bile canalicular or basolateral plasma membranes, by ER. Furthermore, these sorting processes may be regulated by specific transporters within the ER.
Department of Obstetrics and Gynaecology, Ninewells Medical School, University of Dundee, UK.
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Waddell
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Robertson
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Burchell
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Hume
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Burchell
D001663:Bilirubin / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005374:Filtration / Q000379:methods; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D006932:Hyperbilirubinemia / Q000378:metabolism; D007231:Infant, Newborn; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009284:Naphthols / Q000378:metabolism
D005958:Glucosephosphates; D005965:Glucuronates; D009284:Naphthols; C029350:1-naphthol; D019298:Glucose-6-Phosphate; D014453:Glucuronosyltransferase; D001663:Bilirubin