Endocytosis intracellular routes

In most cells, the major route for endocytosis is mediated by the molecule clathrin. Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. A variety of mono- and polyclonal anti-clathrin antibodies are purchasable from Santa Cruz Biotechnology, inc. (http //www.scbt.com/table-clathrin.html). 

The second reason to consider the intracellular enzymes is because of the absorption mechanisms by which macromolecules may cross the intestinal mucosa. There are two possible mechanisms for relatively small macromolecules such as therapeutic peptides and oligonucleotides, they may be able to pass via the paracellular route between the cells, particularly if some absorption enhancers are present. For example, Tsutsumi et al. (2008) have shown in vitro that in the presence of chenodeoxycholate as an absorption enhancer modified oligonucleotides with molecular weights of nearly 3,700 and 7,400 Da could cross rat intestine via the paracellular route. In the case of the paracellular route the macromolecules will not be exposed to the intracellular enzymes and thus they will not be subject to intracellular hydrolysis. However, macromolecules, especially larger ones, will cross the epithelium via the transcellular mechanism of endocytosis. In this case they will be taken into the lysosomes that contain a formidable array of digestive enzymes (see later in Section 1.5.2). 

Endocytosis thus also allows the transfer of an occupied an presumably active receptor from the plasma membrane compartment of the intracellular, cytosolic milieu. As it goes through the route of receptor-mediated endocytosis it has the opportunity of interacting with a collection of distinct membrane-vesicle proteins. Thus,... 

Figure 4.8 Schematic drawing of the mechanisms and routes of drug absorption across intestinal epithelia. Drugs can be absorbed transcellularly [1) and paracellularly (2) by passive diffusion or transcellularly via carrier-mediated transport [3) or endocytosis C4). Enzymes in the brush-border region or intracellular enzymes and the efflux proteins, e.g., P-glycoprotein (5) contribute to the elimination of harmful compounds.

---