Species Differences on Intestinal CYP Expression

Abstract

The CYP450 enzyme family is most responsible for the biotransformation of endobiotic and exobiotic. Eventually, this family will consist of the most abundant drug-metabolizing enzymes. Though the liver is the major metabolizing organ for drugs and xenobiotics, orally administered drugs can be pre-metabolized before reaching systemic circulation. This metabolism takes place in the small intestine, which is the second-largest metabolizing organ after the liver. Because intestinal cells from various laboratory animals can be examined to predict the pre-systemic metabolism of orally administered drugs, this study hopes to shed light on species differences in intestinal gene expression. The most abundant human CYP subfamilies were CYP3A, and the most highly expressed isoform was CYP3A4, which was completely mimicked by monkeys’ intestinal CYP expression. CYP1A1 was expressed in all species' intestines except dogs. Other commonly expressed isoforms for all species were CYP1B1, CYP2E1, CYP2J2, and CYP3A5. Humans, mice, and monkeys have shown the most similarities. The homologies of CYP1A1 and CYP1A2 were found to be identical in monkeys, but substrate specificity varied. Humans have interindividual variation in the expression of enzymes, which is not an attributing problem for other species. In all the species studied, the distribution of enzymes varies with the different segments of the intestine, and the level of protein expression also varies while reaching distal regions. Further summarization of CYP expression in different segments of the small intestines of humans will help in pharmacokinetic studies.