Haley Shannon L, Lamb John G, Franklin Michael R, Constance Jonathan E, Denise Dearing M
Department of Biology, 257 South 1400 East University of Utah, Salt Lake City, UT 84112, United States.
Comp Biochem Physiol C Toxicol Pharmacol. 2007 Nov;146(4):552-60. doi: 10.1016/j.cbpc.2007.06.007. Epub 2007 Jun 30.
Mammalian herbivores routinely consume diets laden with often-toxic xenobiotics, yet the manner in which mammalian herbivores detoxify these plant secondary compounds (PSC) is largely unknown. Theory predicts that specialists rely more heavily on functionalization pathways whereas generalists rely on conjugation pathways to metabolize PSC in their diet. We took a pharmacological approach to determine how a specialist (Neotoma stephensi) of juniper foliage (Juniperus monosperma) and a generalist (N. albigula) may process the same dietary PSC. We investigated the xenobiotic metabolizing enzymes of the specialist and generalist on a control diet and a low (25%) juniper diet. We also examined enzyme activities in the specialist on a high (70%) juniper diet. We assayed for cytochrome P450 concentration and biotransformation activities of three specific cytochrome P450 isozymes (CYP1A, CYP2B, CYP3A), NAD(P)H:quinone oxidoreductase, glutathione conjugation, sulfation and glucuronidation. Results provide partial evidence for the hypothesis in that the specialist and generalist consuming juniper at a level similar to their natural diet, differ in the level of conjugation enzyme activity with generalists having higher activity overall than specialists.
哺乳动物食草动物经常食用富含通常有毒的异生物质的食物,然而哺乳动物食草动物解毒这些植物次生化合物(PSC)的方式在很大程度上尚不清楚。理论预测,专食性动物在很大程度上依赖功能化途径,而广食性动物则依赖共轭途径来代谢其食物中的PSC。我们采用药理学方法来确定杜松树叶(单籽杜松)的专食性动物(斯蒂芬林鼠)和广食性动物(白喉林鼠)如何处理相同的食物PSC。我们研究了专食性动物和广食性动物在对照饮食和低(25%)杜松饮食条件下的异生物质代谢酶。我们还检测了专食性动物在高(70%)杜松饮食条件下的酶活性。我们测定了细胞色素P450浓度以及三种特定细胞色素P450同工酶(CYP1A、CYP2B、CYP3A)、NAD(P)H:醌氧化还原酶、谷胱甘肽共轭、硫酸化和葡萄糖醛酸化的生物转化活性。结果为该假设提供了部分证据,即专食性动物和广食性动物在食用与它们自然饮食水平相似的杜松时,共轭酶活性水平存在差异,广食性动物的总体活性高于专食性动物。