Enzyme kinetics of zearalenone biotransformation: pH and cofactor effects |
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Authors: | H Malekinejad R F Maas-Bakker J Fink-Gremmels |
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Institution: | (1) Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, 3508, TD, Utrecht, The Netherlands |
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Abstract: | The aim of the present study was to investigate the hepatic biotransformation of the mycotoxin zearalenone (ZEA) in vitro using subcellular fractions of pig livers. The dependencies of the enzymatic reactions involved on the enzyme velocity, on the cofactor and on pH were analysed in both the microsomal fraction and the post-mitochondrial cell fraction. Finally, the inhibitory effects of various endogenous substrates on the enzymes involved (3 - and 3 -hydroxysteroid dehydrogenase) were examined. Significant differences were observed between the individual subcellular fractions in terms of prevailing metabolites and absolute amounts of the metabolites produced. Moreover, this study also demonstrated that the reactions for both subcellular fractions of porcine liver are dependent on the cofactor, as -zearalenol ( -ZOL) formation increased in the presence of NADPH, whereas -zearalenol ( -ZOL) production only increased in the presence of NADH (P<0.001). The optimal pH for -ZOL production was pH 5.6 and that for -ZOL formation pH 7.4. Subsequent inhibition studies showed significant inhibitory effects for 5 -androstanedione>androstanedione>pregnenolone on -ZOL formation, whereas -ZOL production was only inhibited by pregnenolone. Finally, the contributions of 3 - and 3 -hydroxysteroid dehydrogenase during the bioconversion of ZEA are discussed in the context of these experiments. |
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Keywords: | Zearalenone -Zearalenol" target="_blank">gif" alt="agr" align="BASELINE" BORDER="0">-Zearalenol -Zearalenol" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0">-Zearalenol Hepatic biotransformation Cofactors Hydroxysteroid dehydrogenase |
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