A specific hydroxysteroid UGT is responsible for the conjugation of aliphatic alcohols in rats: an estimation of the importance of glucuronidation versus oxidation.
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A specific hydroxysteroid UGT is responsible for the conjugation of aliphatic alcohols in rats: an estimation of the importance of glucuronidation versus oxidation. / Iwersen-Bergmann, Stefanie; Schmoldt, A.
In: ALCOHOL, Vol. 15, No. 3, 3, 1998, p. 185-192.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A specific hydroxysteroid UGT is responsible for the conjugation of aliphatic alcohols in rats: an estimation of the importance of glucuronidation versus oxidation.
AU - Iwersen-Bergmann, Stefanie
AU - Schmoldt, A
PY - 1998
Y1 - 1998
N2 - UDP-glucuronosyltransferase (UGT) activity for aliphatic alcohols was determined in microsomal liver fractions of Wistar rats. The rats were pretreated with inducers of cytochrome P450 and UGTs [phenobarbital (PB), beta-naphtoflavone (betaNF), and ethanol (10%)], and inhibition experiments with aliphatic alcohols and specific substrates for UGTs were performed to characterize the UGT form(s) responsible for the glucuronidation of aliphatic alcohols. Several UGT isoforms were purified from liver microsomes of low-androsterone-conjugating activity (LA), controls, and ethanol-pretreated rats by chromatofocusing and affinity chromatography. The results show aliphatic alcohols to be specific substrates for 17beta-hydroxysteroid UGT with considerable glucuronidation rates. This elimination pathway for aliphatic alcohols is not inducible by the tested inducers. Compared with kinetic data of oxidation, glucuronidation is probably the main elimination pathway for alcohols with a longer chain length than C3, especially when oxidation pathways are inhibited by the presence of proportionately high ethanol concentrations.
AB - UDP-glucuronosyltransferase (UGT) activity for aliphatic alcohols was determined in microsomal liver fractions of Wistar rats. The rats were pretreated with inducers of cytochrome P450 and UGTs [phenobarbital (PB), beta-naphtoflavone (betaNF), and ethanol (10%)], and inhibition experiments with aliphatic alcohols and specific substrates for UGTs were performed to characterize the UGT form(s) responsible for the glucuronidation of aliphatic alcohols. Several UGT isoforms were purified from liver microsomes of low-androsterone-conjugating activity (LA), controls, and ethanol-pretreated rats by chromatofocusing and affinity chromatography. The results show aliphatic alcohols to be specific substrates for 17beta-hydroxysteroid UGT with considerable glucuronidation rates. This elimination pathway for aliphatic alcohols is not inducible by the tested inducers. Compared with kinetic data of oxidation, glucuronidation is probably the main elimination pathway for alcohols with a longer chain length than C3, especially when oxidation pathways are inhibited by the presence of proportionately high ethanol concentrations.
KW - Animals
KW - Male
KW - Rats
KW - Substrate Specificity
KW - Rats, Wistar
KW - Hydrogen-Ion Concentration
KW - Binding, Competitive
KW - beta-Naphthoflavone/pharmacology
KW - Enzyme Inhibitors/pharmacology
KW - Oxidation-Reduction
KW - Ethanol/pharmacology
KW - Alcohols/metabolism/pharmacology
KW - Glucuronates/metabolism
KW - Glucuronosyltransferase/metabolism
KW - Hydroxysteroids/metabolism
KW - Microsomes, Liver/drug effects/enzymology
KW - Phenobarbital/pharmacology
KW - Animals
KW - Male
KW - Rats
KW - Substrate Specificity
KW - Rats, Wistar
KW - Hydrogen-Ion Concentration
KW - Binding, Competitive
KW - beta-Naphthoflavone/pharmacology
KW - Enzyme Inhibitors/pharmacology
KW - Oxidation-Reduction
KW - Ethanol/pharmacology
KW - Alcohols/metabolism/pharmacology
KW - Glucuronates/metabolism
KW - Glucuronosyltransferase/metabolism
KW - Hydroxysteroids/metabolism
KW - Microsomes, Liver/drug effects/enzymology
KW - Phenobarbital/pharmacology
M3 - SCORING: Journal article
VL - 15
SP - 185
EP - 192
JO - ALCOHOL
JF - ALCOHOL
SN - 0741-8329
IS - 3
M1 - 3
ER -
