Abstract
In intestinal mucosa of fed adult rats, cytochrome P-450 content and activity of benzpyrene hydroxylase and p-nitroanisole O-demethylase are highest in the upper small intestine and progressively decrease toward the terminal ileum. Among the mucosal cell populations, mature villous tip cells contain 6 to 10 times more cytochrome P-450 and drug-metabolizing activity per mg microsomal protein than epithelial crypt cells. On restriction of dietary iron intake for 48 hr, cytochrome P-450 content and drug-metabolizing enzyme activity of villous tip cells decrease to 42% and 13% of control values, but are restored within 24 hr by oral iron supplementation. These findings suggest that intestinal drug metabolism is localized primarily in upper villous cells of duodenal mucosa, that cytochrome P-450 is synthesized in maturing epithelial cells as they migrate to the top of the mucosal villus and that this process is critically dependent on dietary (luminal) iron.
Published Version
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