Biological Membranes - A. N. Ogurtsov 2012

Biomembrane Electrogenesis
Cotransporter-Mediated Secondary Transport
Transepithelial Transport

Connections between Cells within Tissues and Organs of Multicellular Organisms are formed by specialized structures called Cell junctions. In the simplest case, Intercellular junctions (often also referred to as junctions or connections) are divided into tight junctions and Gap Junctions (see Section 16.1).

Tight junctions seal the intercellular spaces in epithelia and prevent metabolites from passing through the epithelium by bypassing the epithelial cells (Figure 109(a)).

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Figure 109 - Tight intercellular junctions: a - junction between two epithelial cells, b - Structure of a tight junction

Tight junctions are divided into a sealing zone and an adhesion zone.

In the sealing zone, the outer layers of the membranes of adjacent cells fuse, making this zone impermeable to macromolecules and ions.

In the adhesion zone, the membranes are separated by a 10-20 nm gap.

Gap junctions (discussed in more detail below in Section 16.1) connect the cytosols of cells, allowing ions and small molecules to pass from Cell to Cell.

There are two pathways for metabolite Transport Across the epithelium: transcellular and paracellular (Figure 110).

The primary transepithelial transport pathway is the transcellular route. The paracellular pathway, which allows the passage of certain ions and small molecules, is auxiliary and depends on the specific protein COMPOSITION OF THE cell junctions and the physiological state of the epithelial cells.

Figure 110 - Transcellular and paracellular pathways of transepithelial transport

In the case of the intestinal epithelium, nutrient absorption from the intestinal lumen occurs on the luminal side through the apical membrane of epithelial cells, followed by the export of these substances into the bloodstream on the serosal side through the basolateral membrane (Figures 110 and 19).

This two-step process is called transcellular transport.

Intestinal epithelial cells (like those of any other epithelium) are referred to as polarized because the apical and basolateral domains of The Plasma Membrane contain different sets of Membrane Proteins. These two domains of the plasma membrane are separated by tight junctions.

The apical portion of the plasma membrane, which is in contact with the intestinal lumen, is specialized for the absorption of sugars, Amino Acids, and other molecules produced in the lumen by digestive Enzymes. The surface area of the apical membrane is significantly increased by The formation of microvilli, which enhances The rate of metabolite absorption.

Figure 111 shows the membrane proteins that mediate the absorption of glucose from the intestinal lumen into the Blood.

Figure 111 - Transcellular transport of glucose from the intestinal lumen into the blood

In the first step of this process, 2-Na⁺/1-glucose symporters located on the microvillar membranes import glucose molecules from the intestinal lumen against their concentration gradient across the apical surface of the epithelial cell. This symporter couples the energetically unfavorable transport of glucose into The Cell with the energetically favorable transport of two sodium ions into the cell.

In the steady state, all sodium ions transported into the cell via Na⁺/glucose or Na⁺/amino acid symport are pumped out through the basolateral membrane by Na^+/K⁺-ATPases, which are found exclusively in the basolateral membranes of intestinal epithelial cells. As a result, the concentration of Na⁺ ions in the Cytosol of these cells is maintained at a low level. Thus, it can be concluded that the energy source for the first step of transcellular glucose transport is indeed the Hydrolysis of ATP by Na⁺/K⁺-ATPases.

In the second step, glucose (and amino acid) molecules that were concentrated in the cytosol of epithelial cells During the first step move down their concentration gradient across the basolateral membrane into the blood via membrane uniporter proteins. In the case of glucose transport, this uniporter is the GLUT2 protein (see Section 6.5).

The net result of these two steps is The transport of Na⁺ ions, glucose, and amino acids from the intestinal lumen across the intestinal epithelium into the extracellular fluid surrounding the basolateral surface of the epithelial cells. Tight junctions prevent these molecules from diffusing back into the intestinal lumen.

The increase in osmolarity due to the transcellular transport of salts, sugars, and amino acids enhances the osmotic transfer of Water molecules from the intestinal lumen into the blood. Therefore, in a sense, the transported metabolite molecules "carry" water molecules along with them.

This accompanying water flow is utilized for medical purposes in cases of severe dehydration (during dysentery, cholera, and other intestinal infections that cause high mortality, especially in children). In these cases, patients are given an aqueous solution of sugar and salt to drink (together, not separately). As a result of the osmotic water flow from the intestinal lumen into the blood, partial rehydration of the body occurs, which improves the patient's condition and allows for long-term therapy.