Molecular insights into xenobiotic disposition in Australian marsupials

Abstract

During the past two decades, studies of xenobiotic detoxification by molecular biology in diverse organisms have identified many novel environmental adaptations, providing valuable insight into habitat, dietary preferences and general physiology. While xenobiotic detoxification has been extensively studied in eutherian mammals, metabolic data concerning detoxification in Australian marsupials are limited, particularly at the molecular level of the enzymes involved. At present Australia relies heavily on overseas data to determine the possible outcomes of xenobiotic exposure in Australian native fauna. Unlike eutherian mammals, many marsupial herbivores ingest and absorb large amounts of dietary Eucalyptus terpenes. Such quantities would be toxic, even potentially fatal, to human and many other mammalian species. Specialist Eucalyptus herbivores, such as koalas and brushtail possums, have been hypothesised to utilise highly efficient enzyme systems to metabolise terpenes to non-toxic substances that can be readily excreted in the urine. Enzymes that carry out the biotransformation of Eucalyptus terpenes have been partially identified to be the cytochromes P450 (CYP). The aim of this review is to provide a summary of work being undertaken over several years in our laboratories that has provided unique insights into marsupial biology. The focuses of this study are phase I and phase II metabolisms in these unique animals, the multiplicity of metabolising enzymes/pathways involved, induction/inhibition of CYPs/other enzymes by dietary Eucalyptus terpenes and to update current knowledge of xenobiotic metabolism in Australian marsupials. The important role of marsupial genome studies in identifying evolutionary relationships and functions for mammalian genes as well as in conservation, ecology and pest management of marsupial species is also briefly highlighted.