Meeting Abstract
Mammalian herbivores that consume plants high in natural toxins confront the possibility of being poisoned with each meal. The ability of some species to specialize on plants high in toxins is hypothesized to be the result of highly effective detoxification enzymes that rapidly metabolize toxins. We have been testing this hypothesis by characterizing and comparing the detoxification enzymes of a herbivorous woodrat that specializes on juniper with those of the generalist feeder . Consumption of juniper increased the content of P450 enzymes nearly 2x in both species. Ingestion of juniper was reduced in the specialist when P450 enzymes were inhibited by the administration of the general P450 inactivator1-aminobenzotriazole. Of three major xenobiotic metabolizing P450 subfamilies in mammals (CYP1A, CYP2B, CYP3A) only CYP2B increased (2x) in response to juniper consumption based on Western blotting. An in depth analysis of the CYP2B isoforms revealed multiple members in each species and signficiant species differences in the amino acid sequences, with key differences at substrate recognition sites. An analysis of CYP2B function based on hexobarbital clearance demonstrated faster clearance of this compound in the specialist than the generalist. We are currently conducting other assays to compare the turnover and metabolism of juniper-derived substrates by woodrat liver enzymes. The results suggest that P450 enzymes, particularly CYP2B, may be important in ingestion of juniper and the metabolism of juniper toxins. Whether these enzymes can explain the mechanism underlying dietary specialization requires further investigation. NSF IOS 1256383
