Spectroscopic evidence of interaction between 2-allyl-2-isopropylacetamide and cytochrome P-450 of rat liver microsomes |
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Authors: | G D Sweeney J D Rothwell |
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Affiliation: | Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada |
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Abstract: | 2-allyl-2-isopropylacetamide (AIA) causes marked induction of heme synthesis in rats and other species, degrades cytochrome P-450 in the presence of NADPH and causes experimental porphyria. Using difference spectroscopy we sought evidence of an interaction between AIA and P-450 in microsomes prepared from rat liver. AIA alone caused small and variable changes in the spectral properties of liver microsomes but markedly inhibited the Type I spectral change due to hexobarbitone. Phenobarbitone exhibited behaviour qualitatively similar to AIA. It is concluded that AIA binds to cytochrome P-450 without much altering its spectral properties but in such a way as to prevent the change induced by the Type I substrate hexobarbitone. |
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