The four inter-related programs of this grant are proposed by a closely knit group of University of California investigators, with a common interest in the structure function relations of membrane bound enzymes, in electron transport processes, and in the mechanism of action of enzyme inhibitors and toxic substances. The enzymes being investigated include succinate dehydrogenase, fumarate reductase, monoamine oxidases A and B, NADH dehydrogenase, p-cresol methylhydroxylase, nitrate reductase, and copper protein with a role in bacterial electron transport. Numerous aspects of these enzymes will be explored, such as structure by crystallographic techniques, function of Fe-S clusters and the binding sites of covalently and non-covalently bound flavins by mutagenesis. Major efforts will be directed to further the exploration of the carnitine acyltransferases in mitochondria and peroxisomes and to further elucidate the sequence of events which lead from the entry of neurotoxic tetrahydropyridines into the circulation to nigrostriatal cell death.