Title: Studies on the mechanism of action of mammalian hepatic azoreductase—II
Abstract: The effect of carbon monoxide and steapsin solubilization on rat hepatic microsomal azoreductase and NADPH-cytochrome c reductase previously induced with 3-methylcholanthrene and phenobarbital has been investigated. Microsomal azoreductase was inhibited 30–40 per cent in the presence of carbon monoxide, whereas NADPH-cytochrome c reductase and neotetrazolium diaphorase were uneffected. Upon solubilization by steapsin, azoreductase, NADPH-cytochrome c reductase or neotetrazolium diaphorase was not inhibited by carbon monoxide. The percentage of protein solubilized by steapsin in control microsomes did not differ significantly in microsomes obtained from 3-methylcholanthrene or phenobarbital-pretreated animals. Phenobarbital pretreatment increased NADPH-cytochrome c reductase and azoreductase activity and cytochrome P-450. The increased azoreductase activity was blocked by carbon monoxide in intact microsomes, whereas the solubilized preparation was unaffected. The increased azoreductase activity seen after phenobarbital could be correlated directly with the increased cytochrome P-450. Although 3-methylcholanthrene pretreatment did not increase NADPH-cytochrome c reductase or neotetrazolium diaphorase in either the microsomal or solubilized fraction, it did increase both cytochrome P-450 and carbon monoxide sensitive and insensitive microsomal azoreductase. In contrast to phenobarbital, the inductive effect of 3-methyl cholanthrene on azoreductase was destroyed upon solubilization and could not be correlated with increased cytochrome P-450. The data indicate that azo dyes are reduced via: (1) a carbon monoxide sensitive pathway (cytochrome P-450), which is destroyed upon solubilization; (2) a carbon monoxide insensitive pathway (NADPH-cytochrome c reductase), which is not destroyed upon solubilization ; and (3) a 3-methylcholanthrene inducible pathway, which is insensitive to carbon monoxide but sensitive to solubilization.
Publication Year: 1967
Publication Date: 1967-10-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 86
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