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B Burchell

Publications and source records attributed to B Burchell.

187 records · Page 11Linked to original sources
PubMed1972

Development of phenobarbital-sensitive control mechanisms for uridine diphosphate glucuronyltransferase activity in chick embryo liver.

Uridine diphosphate (UDP) glucuronyltransferase activity in chick liver rises at hatching from near zero to adult levels. This rise will occur prematurely in embryo liver during organ culture. Increase in enzyme activity during organ culture differs with embryo age: in liver from 11-day old embryos it ceases at adult values; in liver from 5-day old embryos it continues to much higher-than-adult levels. Phenobarbital added to culture medium accelerates these rises in enzyme activity and elevates the plateau reached in 11-day embryo liver to that observed in 5-day embryo liver. Kinetic analysis of the changes in enzyme activity induced by phenobarbital during culture suggests that the regulatory mechanisms for enzyme activity are different in 5- and 11-day embryo liver and that these differences reflect developmental changes occurring in ovo.

Age Factors↗
PubMedDate not supplied

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.

Bilirubin↗
PubMedDate not supplied

Substrate specificities of two stably expressed human liver UDP-glucuronosyltransferases of the UGT1 gene family.

Two cloned human hepatic UDP-glucuronosyltransferase (UGT) cDNAs were stably expressed in chinese hamster V79 cells. More than 100 drugs and xenobiotics were used as substrates for glucuronidation catalyzed by the cloned human transferases to determine the chemical structures accepted as substrates. UGT HP1 exhibited a limited substrate specificity for planar phenolic compounds, whereas UGT HP4 was more promiscuous in acceptance of non-planar phenols, anthraquinones, flavones, aliphatic alcohols, aromatic carboxylic acids, steroids, and many drugs of varied structure. Levels of HP4 UGT activity toward some substrates were sufficient to allow determination of kinetic parameters for the enzyme reaction. Metabolism of drugs could be studied by addition to the recombinant cell lines in culture, and extraction of the media allowed analysis of glucuronide formation. Data presented herein demonstrate the potential of using these recombinant cell lines for investigation of phase II metabolism by human UGTs.

Animals↗