Metabolite chemical differences between

Importantly, Lindquist et al.53 also document that ascidians can exhibit chemical differences between defensive secondary metabolites among adults and larvae. For example, larvae from colonies of Sigillina cf. signifera contained more tambjamine C, less tambjamine E, and no tambjamine F as compared to adults.65 Moreover, larvae of Trididemnum solidum contain only four of the six didemnins found in adults.53 This could be the result of different selective pressures during planktonic vs. benthic life history phases. In contrast, Lucas et al.44 found no differences in the saponin chemical defenses of the embryos, larvae, and adults of the sea star Acanthaster planci. Clearly, additional studies are needed to expand the evaluation of ontogenetic shifts in defensive chemistry in marine organisms. 

The Medinsky et al. (1995) model also incorporates results from an in vivo study that quantified urinary metabolites in mice treated orally with phenol (Kenyon et al. 1995). Differences in the metabolism of phenol and benzene were incorporated as possible explanations for the differences between these two chemicals in terms of their carcinogenic potency. 

The amount of total residues is generally determined by study with radiolabeled drugs and is expressed as the parent drug equivalent in milligrams per kilogram of the food. Bound metabolites can be measured as the difference between the total and extractable residue. Microbiological assays measure the parent molecule and its bioactive metabolites immunochemical assays measure the parent molecule and closely chemically related metabolites. 

Differences in Ligand Inducibility. Hiunan PPARa is not more sensitive than rodent PPARa to chemical activation. Most compounds activate the rodent receptor better or exhibit no differences between species. A munber of environmentally relevant chemicals and hypolipidemic agents were able to activate rat or mouse PPARa at lower concentrations or to higher absolute levels than hPPARa in side-by-side trans-activation studies. These PPARa activators include WY-14,643 (Keller et al. 1997 Maloney and Waxman 1999 Takacs and Abbott 2007), PFOA (Maloney and Waxman 1999), perfluorooctanesulfonate (Shipley et al. 2004 Takacs and Abbott 2007), and a number of phthalate ester metabolites [Bility et al. (2004) and summarized in Corton and Lapinskas (2005)]. Some PPARa activators show no differences between activation of the mouse and hiunan PPARa, including TCA, dichloroacetate, 2-ethylhexanoic acid (Maloney and Waxman 1999), a number of phthalates (Bility et al. 2004), clofibrate (Keller et al. 1993), and PFOA (Vanden Heuvel et al. 2006). Only perfluorooctanesulfonamide (Shipley et al. 2004) was shown to modestly activate the human but not the rodent PPARa at one lower dose (25 jM in human versus 34 pM mouse). Overall, the data indicate that hPPARa is no more sensitive than the mouse or rat PPARa to significant activation by environmentally relevant PPARa activators. 

Assistance with chemical synthesis efforts to select or eliminate compounds Assistant with synthetic efforts to block or enhance metabolism Identification of simple and major metabolites, for example, dealkylations and conjugations such as glucuronide Determination of metabolite differences between species Identification of potential pharmacologically active or toxic metabolites... 

---