Pathway trans-cellular

Fig. 12.1 Schematic representation of the three transepithelial intestinal pathways (a) trans-cellular active transport, (b) transcellular passive transport, (c) paracellular transport (Fasano...

The compounds can cross the membranes by passive processes, which depend only on the concentration gradient on both sides of the barrier, or by active ones, which are mediated by the interaction of the compound with a protein. The passive processes of the epithelial cells in the gastrointestinal tract include passive transport through the cell (trans-cellular pathway) or in the space between the cells (para-cellular pathway) [18]. 

Figure 1 Parallel pathways of intestinal absorption (1) paracellular pathway, (2) trans-cellular pathway, (2a) carrier-mediated, (2b) passive diffusion, (2c) receptor-mediated endocytosis, and (3) mediated efflux pathway. (From Ref. 30.)...

The microvillus membrane of the absorptive cell has a thickness of 9.5-11.5 nm, which is somewhat thicker than normal biological membranes. It is folded into microvilli (about 200,000/mm2 in the human jejunum [11]), and increases the surface of the intestine by a factor of 20. Microvilli contract, and, during contraction the fibers in the core slide down toward the underlying terminal web. In this region, the movement of drugs and other molecules will not only be diffusive but also agitative. Molecules passing the membrane are absorbed by the trans-cellular pathway. 

Thompson SE, Cavitt J, Audus KL, 1994. Leucine-enkephalin effects on paracellular and trans-cellular permeation pathways across brain microvessel endothelial-cell monolayers. / Cardiovasc... 

Figure 1 The mode of action for bacterial AB-type exotoxins. AB-toxins are enzymes that modify specific substrate molecules in the cytosol of eukaryotic cells. Besides the enzyme domain (A-domain), AB-toxins have a binding/translocation domain (B-domain) that specifically interacts with a cell-surface receptor and facilitates internalization of the toxin into cellular transport vesicles, such as endosomes. In many cases, the B-domain mediates translocation of the A-domain into the cytosol by pore formation in cellular membranes. By following receptor-mediated endocytosis, AB-type toxins exploit normal vesicle traffic pathways into cells. One type of toxin escapes from early acidified endosomes (EE) into the cytosol, thus they are referred to as short-trip-toxins . In contrast, the long-trip-toxins take a retrograde route from early endosomes (EE) through late endosomes (LE), trans-Golgi network (TGN), and Golgi apparatus into the endoplasmic reticulum (ER) from where the A-domains translocate into the cytosol to modify specific substrates.

The bradykinin receptor is a member of a family of receptors for which an intracellular interaction with a G-protein is a critical part of the signal transduction pathway following agonist binding. Structurally, these G-protein-coupled receptors extend from beyond the extracellular boundary of the cell membrane into the cytoplasm. The tertiary structure is such that the protein crosses the bilayer of the cell membrane seven times, thus forming three intracellular loops, three extracellular loops, and giving rise to cytoplasmic C-terminal and extra-cellular N-terminal strands. It is generally presumed that the transmembrane domains of these receptors exist as a bundle of helical strands. This assumption is derived primarily from the known structure of the trans-membrane portions of a structurally related protein, bacteriorhodopsin [40]. 

The Reduction Reactions. The object of the next three reactions (steps 4 to 6 in fig. 18.12a) is to reduce the 3-carbonyl group to a methylene group. The carbonyl is first reduced to a hydroxyl by 3-ketoacyl-ACP reductase. Next, the hydroxyl is removed by a dehydration reaction catalyzed by 3-hydroxyacyl-ACP dehydrase with the formation of a trans double bond. This double bond is reduced by NADPH catalyzed by 2,3-trans-enoyl-ACP reductase. Chemically, these reactions are nearly the same as the reverse of three steps in the j6-oxidation pathway except that the hydroxyl group is in the D-configuration for fatty acid synthesis and in the L-configuration for /3 oxidation (compare figs. 18.4a and 18.12a). Also remember that different cofactors, enzymes and cellular compartments are used in the reactions of fatty acid biosynthesis and degradation. 

Mechanistic pathways 1 and 2 involving isomerization catalysis and holding of unfolded polypeptide chains can be discussed in relation to all subfamilies of peptide bond cis-trans isomerases. In contrast, only members of the two families of cydophilins and FKBP, were found to play a role in presenting physiological ligands to further cellular constituents. 

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