Cytochrome P450 Expression in the Liver of Food-Producing Animals

Abstract

A number of enzyme systems participate in the metabolism of chemicals, but undoubtedly the most important are the cytochromes P450 (CYP). It is a versatile enzyme system, capable of metabolising structurally diverse chemicals. To achieve this broad substrate specificity it exists as a superfamily of enzymes, each family being characterised by different substrate specificity; families CYP1, CYP2 and CYP3 are responsible for the metabolism of exogenous chemicals. Although our current knowledge of the expression and function of cytochromes P450 in humans and laboratory animals is extensive, little is known about this enzyme system in food-producing animals, despite its dominant role in the metabolism of veterinary drugs, and the crucial role it plays in controlling the levels of drug and other chemical residues in edible tissues and food products that humans consume, a matter of major current concern. Most studies dealing with the expression of cytochromes P450 in food-producing animals utilised substrate probes defined in rats and humans and/or antibodies raised to rat or human antigens. Such an approach can prove misleading as it assumes that orthologue proteins in other animals share the same substrate specificity and, moreover, although antibodies raised to human or rat antigens may recognise epitopes in other species, they do not constitute unequivocal proof that the detected proteins are structurally identical. Despite these drawbacks, there is substantial experimental evidence that CYP1, CYP2 and CYP3 families are expressed in food-producing animals, but their role in the metabolism of veterinary drugs and other xenobiotics has not been addressed.