Xenobiotic metabolizing enzyme activities in wild herbivore specialists and generalists, genus Neotoma

The challenge of consuming plant compounds that have harmful physiological effects is an unavoidable consequence of an herbivorous diet and requires mechanisms to safely metabolize and eliminate them after consumption. A fundamental goal in plant-herbivore research has been to identify mechanisms used by herbivores to metabolize these defensive plant secondary compounds (PSC). In the course of evolution, pressures from predators (i.e., microbes, fungus, and herbivores) have selected for particularly noxious PSC that, when consumed, can hinder growth and cause cellular damage and metabolic disruption. The physiological challenge of consuming PSC is predicted to affect the feeding strategies of mammalian herbivores.; Herbivores can be categorized as having specialist or generalist feeding strategies. Although most mammalian herbivores can tolerate the small quantities of PSC in a generalist diet, the ability to consume large quantities in a specialist diet composed primarily of a single plant is rare. Existing mammalian specialists are believed to express a unique pattern of induced biotransformation enzymes that permit elimination of the large concentrations of PSC found in a specialist diet.; The research in this dissertation took a pharmacological approach to understand how specialist and generalist pairs of woodrat herbivores process the same dietary PSC by investigating the presence and degree of differences in specific biotransformation pathways between three pairs of closely related specialist and generalist herbivores. Using well-established in vitro pharmacological assays, we measured activity in five primary xenobiotic metabolizing enzymes and three specific cytochrome P450 isozymes. Chapters 2 and 3 test a long-standing hypothesis that specialists on their natural diet will have greater activity of functionalization enzymes and lower activity of conjugation enzymes than generalists to reduce the cost of PSC biotransformation. Though supported in previous research targeting Eucalyptus specialists and generalists, results presented here indicate that the hypothesis proposed cannot be generalized to all specialist/generalist strategies. In Chapter 4, the biotransformation enzyme activities in a recently evolved specialist population of woodrat were investigated. This research suggests that a population of woodrat herbivores have developed novel xenobiotic enzyme regulation in response to PSC found in creosote that have potentially allowed for dietary specialization over a relatively a short period.