Single pathway modeling

Model Types. If it is determined that exposure pathways of interest intersect more than one of the media, the analyst is faced with the need to link together single media models (or to apply existing multimedia models). Despite claims to the contrary, there is probably no single model that is appropriate to all problems. Thus, a hybrid combination of boundary... 

The relationship between the different conductances of the glutamate transporter is not well-understood. The structural basis for these conductances and whether the anions and glutamate permeate the same pore of the transporter protein is not known. Sonders and Amara (40) proposed two models a single pathway for substrate and the uncoupled anion movement (Fig. 3A), or multiple permeation pathways in a single transporter molecule (Fig. 3B) (40). This idea will be discussed further in relation to what is known about the quaternary structure of glutamate transporters. 

Despite the success of the comparatively simple models presented so far, they implicitly assume that the skin barrier may be modeled by a homogeneous membrane—which implies that the properties of the barrier do not change with depth and that there exists only a single pathway through the barrier. Obviously, skin is not a homogeneous membrane and therefore in several studies the simple model was extended to include several subsequent skin layers. In addition, possible transport along hair follicles and sweat ducts, for example, was sometimes included. 

Staines, H. M., Ashmore, S., Felgate, H., Moore, J., Powell, T., and Ellory, J. C. (2006). Solute transport via the new permeability pathways in Plasmodium falciparum-infected human red blood cells is not consistent with a simple single-channel model. Blood 108,3187-3194. Staines, H. M., Ellory, J. C., and Kirk, K. (2001). Perturbation of the pump-leak balance for Na(+) and K(+) in malaria-infected erythrocytes. Am. J. Physiol. Cell Physiol. 280, C1576-C1587. 

Put all of the kinetic and equilibrium data together into a single, complete model for the reaction sequence, quantitatively accounting for every experimental result by the complete reaction pathway. Computer simulation can be used to establish that all experimental results can be understood quantitatively in terms of a single mechanism. 

Single or Multiple Pathways Modeling A single microbial model (one culture) may exhibit the entire complex of divergent routes of mammalian metabolism seen with a particular substrate in numerous mammalian species. For example, Cunninghamella bainieri was shown to produce several known oxidative mammalian metabolites of N-n-propylamphetamine. Alternatively, one culture may exhibit a single route of metabolism in lieu of all others. This is particularly useful if the pathway is minor and/or quantitatively masked by other routes of metabolism in mammals, and thus hard to study. In this case, the ultimate "microbial model" may be a composite of cultures, each exhibiting the individual reactions. 

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