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Titolo:
DECONJUGATION OF BILIRUBIN-IX-ALPHA GLUCURONIDES - A PHYSIOLOGICAL-ROLE OF HEPATIC-MICROSOMAL BETA-GLUCURONIDASE
Autore:
WHITING JF; NARCISO JP; CHAPMAN V; RANSIL BJ; SWANK RT; GOLLAN JL;
Indirizzi:
HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV GASTROENTEROL,75 FRANCIS ST BOSTON MA 02115 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV GASTROENTEROL,75 FRANCIS ST BOSTON MA 02115 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG BOSTON MA 02115 BETH ISRAEL HOSP,CHARLES A DANA RES INST BOSTON MA 02215 BETH ISRAEL HOSP,DEPT MED,HARVARD THORNDIKE LAB BOSTON MA 02215 HARVARD UNIV,SCH MED BOSTON MA 02115 ROSWELL PK CANC INST BUFFALO NY 14214
Titolo Testata:
The Journal of biological chemistry
fascicolo: 31, volume: 268, anno: 1993,
pagine: 23197 - 23201
SICI:
0021-9258(1993)268:31<23197:DOBG-A>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
UNCONJUGATED BILIRUBIN; NATIVE BILE; UDP-GLUCURONYLTRANSFERASE; RAT; EGASYN; MONOGLUCURONIDE; CHOLELITHIASIS; DIGLUCURONIDE; HYDROLYSIS; GALLSTONES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
J.F. Whiting et al., "DECONJUGATION OF BILIRUBIN-IX-ALPHA GLUCURONIDES - A PHYSIOLOGICAL-ROLE OF HEPATIC-MICROSOMAL BETA-GLUCURONIDASE", The Journal of biological chemistry, 268(31), 1993, pp. 23197-23201

Abstract

Beta-glucuronidase is an acid hydrolase located in both the lysosomaland microsomal compartments of the hepatocyte. The function of the latter remains undefined. We postulated that microsomal beta-glucuronidase may be responsible for the deconjugation of bilirubin-IXalpha glucuronides which are synthesized primarily in the hepatic microsomal compartment. We utilized two unique congenic strains of mice to characterize the role of hepatic beta-glucuronidase in the metabolism and disposition of bilirubin-IXalpha; the first exhibited less than 1% of total hepatic beta-glucuronidase activity (ATM), the second lacked only the microsomal enzyme activity (AT1). The biliary excretion of bilirubin-IXalpha conjugates was quantitated using reverse-phase high performanceliquid chromatography. Under basal conditions, there was a 2-fold increase in the biliary excretion of bilirubin-IXalpha monoglucuronides and total glucuronides in the AT1 and ATM mutants compared to the normal controls. When the plasma bilirubin-IXalpha level was increased to almost-equal-to 7 mg/dl to simulate hyperbilirubinemia, by intravenous administration of [C-14]bilirubin-IXalpha, mathematical modeling of the biliary excretion curves of bilirubin-IXalpha glucuronides revealed qualitative differences between control and mutant animals, whereas both mutant groups were similar. Collectively, these data demonstrate that microsomal beta-glucuronidase modulates the net rate of bilirubin-IXalpha glucuronidation and glucuronide excretion in bile, under both basal and hyperbilirubinemic conditions, and that lysosomal beta-glucuronidase has no such effects. Hepatic microsomal beta-glucuronidase appears likely to influence the biliary excretion and hence the hepatic elimination of endogenous and xenobiotic substrates (e.g. carcinogens) which undergo hepatic glucuronidation.

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Documento generato il 11/07/20 alle ore 06:48:35