Figure 2.6 Sialic acid.

2 days to move to the region of the tips of the villi, where they are then shed into the lumen. A schematic view of the surface of the epithelial cells shows a further 10-30-fold surface expansion [62,63,69] structures, in the form of microvilli on the luminal side of the cell layer, as shown in Fig. 2.5.

The villi and microvilli structures are found in highest density in the duodenum, jejunum, and ileum, and in lower density in a short section of the proximal colon [66]. The microvilli have glycoproteins (the glycocalyx) protruding into the luminal fluid. There is residual negative charge in the glycoproteins. Some cells in the monolayer are known as goblet cells (not shown in Figs. 2.4 and 2.5), whose function is to produce the mucus layer that blankets the glycocalyx. The mucus layer is composed of a high-molecular-weight (HMW) (2 x 106 Da) glycoprotein, which is 90% oligosaccharide, rich in sialic acid (Fig. 2.6) residues, imparting negative charge to the layer [63]. Studies of the diffusion of drug molecules through the mucus layer suggest that lipophilic molecules are slowed by it [72].

The glycocalyx and the mucus layer make up the structure of the unstirred water layer (UWL) [73]. The thickness of the UWL is estimated to be 30-100 mm in vivo, consistent with very efficient stirring effects [74]. In isolated tissue (in the absence of stirring), the mucus layer is 300-700 mm thick [73]. The pH in the unstirred water layer is ^5.2-6.2, and might be regulated independently of the luminal pH (Section 2.3). The mucus layer may play a role in regulating the epithelial cell surface pH [73].

The membrane surface facing the lumen is called the apical surface, and the membrane surface on the side facing blood is called the basolateral surface. The intestinal cells are joined at the tight junctions [63,75]. These junctions have pores that can allow small molecules (MW < 200 Da) to diffuse through in aqueous solution. In the jejunum, the pores are ^7-9 A in size. In the ileum the junctions are tighter, and pores are ^3-4 A in size (i.e., dimensions of mannitol) [63].

The apical surface is loaded with more than 20 different digestive enzymes and proteins; the protein : lipid ratio is high: 1.7 : 1 [63]. The half-life of these proteins is ^6-12 h, whereas the epithelial cells last 2-3 days. So the cell must replace these constituents without depolarizing itself. The cytoskeleton may play a role

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