Differential induction of UDP-glucuronosyltransferases and their ‘permanent induction’ in pre-neoplastic rat liver

Bock, Karl Walter; Lilienblum, Werner; Ullrich, D.; Fischer, Gösta

doi:10.1042/bst0120055

Cited by 8 publications

(1 citation statement)

References 5 publications

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“…For monoglucuronide formation of BaP-and chrysene-3,6-quinol target sizes were 118 ± 33 and 109 ± 21 kDa, respectively (in agreement with the existence of dimers) whereas for diglucuronide formation target sizes were 218 ± 24 and 192 ± 34 kDa, respectively, suggesting the formation of tetramers. It should be noted that in early enzyme purification studies, gel filtration in presence of detergents revealed peaks at the position of tetrameric UGT complexes [41,42]. In diglucuronide formation some dimers may loosely interact in ER membranes to form tetramers ( Fig.…”

Section: Diglucuronide Formation By Ugt Tetramersmentioning

confidence: 98%

Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: Advances and open questions

Bock

Köhle

2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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Section: Diglucuronide Formation By Ugt Tetramersmentioning

confidence: 98%

Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: Advances and open questions

Bock

Köhle

2009

Biochemical Pharmacology

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UDP-Glucuronyltransferases and Their Toxicological Significance

Bock

Bock-Hennig

Fischer

et al. 1986

Biological Reactive Intermediates III

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The role of conjugation reactions in detoxication

et al. 1987

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The role of conjugating enzymes is best understood by looking at the interaction between phase I (mostly cytochromes P-450) and phase II (conjugation) enzymes of drug metabolism. A balance between phase I and II enzymes of detoxication largely determines the disposition to drug toxicity. Reactive electrophilic metabolites, generated by phase I enzymes, are often controlled by GSH-transferases, whereas nucleophilic metabolites such as phenols are controlled by UDP-glucuronosyltransferases (GT) and sulfotransferases. It is more and more recognized that the control of the more stable and more abundant nucleophiles is as important as the control of electrophiles, since the former can be readily converted to electrophiles. For example, phenols and quinols can undergo quinone/quinol redox-cycles with the generation of reactive oxygen species. In the case of benzo(a)pyrene-3,6-quinol toxicity can be prevented by glucuronidation. Conjugating enzymes consist of families of isoenzymes with distinct but overlapping substrate specificity. Rather than dealing with individual isoenzymes, adaptive programs are emphasized by which gene expression of a battery of phase I and II enzymes is turned on by certain types of inducing agents. Mechanistically best known is the program turned on by 3-methylcholanthrene-type inducers which includes enhanced synthesis of certain isoenzymes of cytochrome P-450, GT and probably GSH-transferase. The program may adapt the organism to efficiently detoxify and eliminate aromatic compounds such as benzo(a)pyrene. Evidence is presented that this program exists in both rodents and humans.(ABSTRACT TRUNCATED AT 250 WORDS)

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Differential induction of UDP-glucuronosyltransferases and their ‘permanent induction’ in pre-neoplastic rat liver

Cited by 8 publications

References 5 publications

Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: Advances and open questions

Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: Advances and open questions

UDP-Glucuronyltransferases and Their Toxicological Significance

The role of conjugation reactions in detoxication

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