Bile acid transportation system

Ileal lipid-binding protein (ILEPs) and other fatty acid binding proteins (FABPs) were the targets of a CRID/CPCA study by Kurz et al. [14]. ILEP is a cytosolic lipid 

For a first model, Kurz et al. used 30 conformers of human and pig ILBP obtained from NMR investigations. In the CPCA score plot, this resulted in a clear grouping PC 1 revealed a separation of complexed from uncomplexed ILBPs, whereas PC 2 separated human and porcine ILBP conformers. 

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All bile acid transport systems possess a high reserve capacity, the potential of which greatly exceeds the normal maximum secretion level. Bile acid cross-over from the enterohepatic into the peripheral circulation arises only in the case of massive disturbances in secretion (e.g. in cholestasis). The approx. 1% proportion of bile acids present in the peripheral system remains constant, both pre- and post-prandially. The first-pass elimination of bile acids from the portal blood reaches 70-90%, depending on their type and conjugation status. The bile acids have a half-life of 2-3 days. 

Wess, G., Kramer, W., Han. X.B.. Bock. K., Enhsen, A., Glombik, H., Baringhaus. K.-H., Boger, G., Urmann, M., Hoffmann, A., and Ealk. E.. Synthesis and biological activity of bile acid-derived HMG-CoA reductase inhibitors. The role of 21-methyl in recognition of HMG-CoA reductase and the deal bile acid transport system. J. Med. Chem.. 31, 3240, 1994. 

Kurz, M., Brachvogel, V., Matter, H., Stenge-lin, S., Thuring, H., and Hamer, W. (2003) Insights into the bile acid transportation system the human ileal lipid-binding pro-tein-cholyltaurine complex and its comparison with homologous structures. Proteins 50, 312-328. 

When applied to intact cells, different factors should be considered. The microcystins, cantharidin, and endothal are not permeable across the plasmalem-ma but may be taken up by hepatocytes via the bile acid transport system (Eriksson et al., 1990). A derivative of endothal, endothal thioanhydride, is permeable across the cell membrane (M. Hirano and F. Er-dddi, unpublished observations). Thus permeability across lipid bilayers is one consideration. In addition, the potency of inhibitors used with intact cells always appears less than the in vitro assays. The potency with intact cells is often 10- to 100-fold less sensitive. For example, with 3T3 fibroblasts, external concentrations above 10 nM were required to elicit shape changes (Chartier et al., 1991). This difference in dose dependence could be due to inefficient uptake by the cells or preferential localization of the inhibitor with lipids. Cohen et al. (1989) suggested that the higher concentrations required with intact cells reflect the intracellular concentration of the targeted phosphatase. 

In a structure activity investigation, the following structural elements necessary for the molecular recognition of a bile acid by the ileal Na /bile acid transport system were identified [21,22] ... 

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