Enterocytes brush border

Kozakova H, Rehakova Z, Kohnska J. Bifidobacterium bifidum monoassociation of gnotobiotic mice effect on enterocyte brush-border enzymes. Folia Microbiol (Praha). 2001 46 573—576. 

The first member of this class, acarbose, was introduced in the early 1990s. a-Glucosidase inhibitors slow the intestinal process of carbohydrate digestion by competitive inhibition of the activity of a-glucosidase enzymes located in the brush border of the enterocytes... 

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

Mucosal brush border membrane vesicles and basolateral membrane vesicles can be isolated to study solute uptake across specific enterocyte boundaries. These more isolated vesicle systems allow for investigation of solute transport across a particular membrane barrier and permit separation of membrane trans-... 

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

Peterson, M. and Mooseker, M.S., Characterization of the enterocyte-like brush border cytoskeleton of the C2Bbe clones of the human intestinal cell line, Caco-2, ]. Cell Sci., 102,581, 1992. 

The layer of water adjacent to the absorptive membrane of the enterocyte is essentially unstirred. It can be visualized as a series of water lamellas, each progressively more stirred from the gut wall toward the lumen bulk. For BCS class 2 compounds the rate of permeation through the brush border is fast and the diffusion across the unstirred water layer (UWL) is the rate-limiting step in the permeation process. The thickness of the UWL in human jejunum was measured and found to be over 500 pm [3]. Owing to its thickness and hydrophilicity, the UWL may represent a major permeability barrier to the absorption of lipophilic compounds. The second mechanism by which the UWL functions act as a barrier to drug absorption is its effective surface area. The ratio of the surface area of the UWL to that of the underlying brush border membrane is at least 1 500 [4], i.e., this layer reduces the effective surface area available for the absorption of lipophilic compounds and hence impairs its bioavailability. 

Absorption of cholesterol in the small intestine contributes to maintaining whole-body cholesterol homeostasis, yet the mechanisms of absorption have not been completely defined. For many years it was believed that cholesterol, a normal component of cell membranes, simply diffused through the brush border membrane of enterocytes (Grundy, 1983 Westergaard and Dietschy, 1974). However, the discovery of specific transporters, receptors,... 

This article focuses on specific dietary components—whether naturally occurring or added as food ingredients—known to interfere with the mechanisms of cholesterol absorption. An overview of cholesterol absorption is provided and emphasizes the critical role of bile acids and micelle formation in solubilizing cholesterol for transport to the brush border membrane of enterocytes. Where applicable, information is also included about commercial food ingredients that are specifically used as cholesterollowering agents. 

FIG. 2 Transport of cholesterol (CHOL) and plant sterols (PS) in the enterocyte. CHOL, PS, and other lipids are solubilized in micelles that deliver the lipids to the brush border membrane. CHOL and PS are transported into the enterocyte by NPC1L1. Nearly all of the PS are redirected back to the intestinal lumen by the transporters ABCG5 and ABCG8. The extent to which CHOL is transported by ABCG5 and ABCG8 is not known. CHOL within the enterocyte is packaged into lipoproteins (chylomicrons) and secreted into lymph and eventually the bloodstream for transport to the liver. 

Figure 1.1 shows the major sites of enzyme activity in the GI tract, and we will consider each of these in turn. While most of the enzymes that hydrolyse macromolecules enter the gut in the pancreatic fluid and hence are found in the lumen of the gut, there is significant peptidase activity located on the membranes of the intestinal cells, the so-called brush border. Consideration should also be given to the enzymes that are located inside the cells of the intestinal mucosa, namely, the epithelial cells or enterocytes. This is for two reasons first, the intestinal mucosa has a turnover of 3-6 days in humans and this means that the enterocytes are constantly being sloughed-off into the lumen of the gut. Thus intracellular enzymes and brush border enzymes will be found in the lumen of the gut, though the precise quantity is difficult to assess (see later in Section 1.6). 

---