Cytochrome P450 Enzymes: Identification, Diversity, and Potential Functions in Marine Invertebrates

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9631128 Snyder Cytochrome P450 enzymes are perhaps the most diverse family of proteins in nature. They are found in all organisms thus far examined and have extensive abilities to metabolize foreign chemicals (xenobiotics) and endogenous molecules such as steroids and fatty acids. One of the driving forces for P450 diversification is thought to be the appearance of toxic chemicals in the diet, the so-called plant-animal warfare" hypothesis. In mammals, one hundred or more P450 forms may exist in a single individual, each with its own metabolic capabilities. Likewise, insects appear to have a large number of P450 forms, some involved in insecticide and dietary plant allelochemical resistance. Marine invertebrates also have demonstrable P450 enzymatic activities that are inducible by exposure to pollutants, though virtually nothing is known about the role of detoxification enzymes in marine invertebrate to dietary chemicals. New information on this group of enzymes may help explain aspects of individual species diet and metabolism as well as identify factors that affect tolerance to other xenobiotic exposures. The investigator proposes to utilize molecular cloning approaches to isolate and identify new cytochrome P450 genes from several marine invertebrate species representing three different Phyla (Aim 1). Those data will provide the first estimate of the diversity of this large protein superfamily among marine invertebrates. The induction of gene expression for selected new proteins belonging to this family will be studied in both field collected species and in controlled laboratory feeding experiments (Aim 2). Antibodies will be produced to several new forms for the design of sensitive immunological assays to measure P450 induction in response to toxin exposures (Aim 3). Since there are currently no marine invertebrate P450 sequences known, these studies will provide much needed information about the diversity of these important enzymes. The results will allow comparisons concer ning the evolution and functions of detoxification enzymes between marine and terrestrial organisms. An eventual goal is the development of methods that will test species-specific responses following exposure to natural and artificial toxicants.