Sublobular distribution of transferases and hydrolases associated with glucuronide, sulfate and glutathione conjugation in human liver.
Activities of glucuronosyltransferase, sulfotransferase, glutathione S-transferase, beta-glucuronidase and sulfatase were determined in microdissected samples of periportal and pericentral sublobular regions from four human livers obtained at immediate autopsy. New methods are presented for the microdetermination of sulfotransferase and sulfatase activities in microdissected samples weighing 0.1 to 4 micrograms dry weight using umbelliferone and 4-methylumbelliferone sulfate as substrates. The three transferases were distributed heterogeneously across the liver lobule. Glucuronosyltransferase and glutathione S-transferase were localized predominantly in pericentral regions. In contrast, sulfotransferase activity was greater in periportal than pericentral regions. Average activities for glucuronosyltransferase and sulfotransferase were 23, and 50 mumoles X gm dry wt-1 X hr-1, respectively, in periportal regions, and 34 and 38 mumoles X gm dry st-1 X hr-1, respectively, in pericentral regions. Activities of glutathione S-transferase were considerably higher than those of the other transferases and were 8.3 mmoles X gm dry wt-1 X hr-1 in periportal areas and 12.2 mmoles X gm dry wt-1 hr-1 in pericentral areas. The two hydrolases studied, beta-glucuronidase and sulfatase, were evenly distributed across the liver lobule. The presence of significant hydrolase and transferase activities in both zones of the liver lobule supports the idea that net production of both sulfate and glucuronide conjugates may be influenced by futile cycling of conjugation-deconjugation reactions in both zones of the liver. Based on enhanced formation of sulfate but not glucuronide conjugates in homogenates of human liver treated with inhibitors of the hydrolases, it is suggested that futile cycling is more pertinent to the regulation of sulfation than glucuronidation.
D000293:Adolescent; D000328:Adult; D015239:Arylsulfotransferase; D005966:Glucuronidase / Q000032:analysis; D014453:Glucuronosyltransferase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006651:Histocytochemistry; D006801:Humans; D006867:Hydrolases / Q000032:analysis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D013429:Sulfatases / Q000032:analysis; D013466:Sulfurtransferases / Q000032:analysis; D014166:Transferases / Q000032:analysis*
D014166:Transferases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D013466:Sulfurtransferases; D015239:Arylsulfotransferase; D006867:Hydrolases; D013429:Sulfatases; D005966:Glucuronidase