SHAH ABDUL LATIF UNIVERSITY KHAIRPUR

Tranportation Through Epithelial Cells

Biomembrane and Cell Signalling

By: Abdul-Rahman Shaikh , Aamir , Sadam & Muhammad-bux ( BS P-III & Previous) BIOCHEMISTRY

Transpotation through Epithelial cells:Epithelia form linings throughout the body. In the small intestine, for instance, the simple columnar epithelium forms a barrier that separates the lumen from the internal environment of the body

(note that the internal environment in which body cells exist is the extracellular fluid or ECF).The epithelium forms a barrier because cells are linked by tight junctions, which prevent many substances from diffusing between adjacent cells. 

For a substance to cross the epithelium, it must be transported across the cell's plasma membranes by membrane transporters.The apical plasma membrane faces the lumen. In the drawing at the right, the apical plasma membrane is drawn as a wavy line, because intestinal epithelial

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cells have a high degree of apical plasma membrane folding to increase the surface area available for membrane transport (these apical plasma membrane folds are known as microvilli). The basolateral plasma membrane faces the ECF. Epithelial cells are able to transport substances in one

direction across the epithelium because different sets of transporters are localized in either the apical or basolateral membranes. Absorption is the means whereby nutrients such as glucose are taken into the body to nourish cells.

Glucose is transported across the apical plasma membrane of the intestine by the sodium-glucose cotransporter (purple).Because transport of Na+ and glucose is coupled, we need to add the free energy inherent in Na+ transport to the free energy inherent in glucose transport to get the overall free energy for

the process. Just after a meal, there will be abundant glucose in the lumen of the intestine, favoring absorption. Towards the end of the absorptive phase of a meal, however, the cotransporter is still able to move glucose into the cell (uphill against its concentration gradient) because of the strong Na+ concentration

gradient. The Na+ gradient is established by the Na+/K+-ATPase (red), which is located on the basolateral membrane. The activity of the cotransporter increases the glucose concentration inside the cells, allowing glucose to be transported into the ECF via the glucose transporter (blue).

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Facilitated diffusion of glucose into the ECF is a passive process, since glucose flows down its concentration gradient.A therapy that takes advantage of this absorption mechanism is oral rehydration therapy. Oral rehydration therapy is a life saving treatment for people with severe diarrhea due to intestinal

infections such as cholera. Fluid loss from the gastrointestinal tract depletes the ECF. The goal in oral rehydration is to expand the ECF. This requires getting Na+ absorbed into the body, since the amount of Na+ in the ECF is the major determinant of ECF volume. Because both Na+ and glucose need to bind to the

sodium-glucose cotransporter for transport to occur, glucose is included in oral rehydration solutions to help speed absorption of Na+.

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About 1500 ml of fluid per day is moved from the extracellular fluid into the lumen of the small intestine in order to provide lubrication that can protect the epithelium and help with intestinal motility. The mechanism for fluid secretion is that solutes are moved across the epithelium, which then draw

water into the lumen by osmosis. The rate-limiting and regulated step in intestinal secretion is the movement of Cl- ions across the apical plasma membrane.The important proteins involved in secretion are diagrammed in the figure. First, Cl- is transported into the epithelial cell by a cotransporter expressed on

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the basolateral membrane. As with the previous example, the Na+ gradient, established by the Na+/K+-ATPase, provides the energy to power transport of ions into the cell (this cotransporter moves 2 Cl-, one K+, and one Na+ ion with each round of transport). Cl- flows down its concentration gradient into the

lumen via the Cl- channel CFTR (green) located on the apical plasma membrane. (Not shown is that Na+ also flows into the lumen, by a passive mechanism). The CFTR protein is a member of the ATP-binding cassette (ABC) protein family. CFTR is an atypical ABC protein; like other members of the ABC

protein family, it binds ATP, but in this case ATP binding is used to open an ion channel. Importantly, the CFTR protein also has a regulatory domain that is phosphorylated by protein kinase A (PKA), also known as cAMP-dependent kinase. Intestinal secretion is turned on when a regulatory molecule binds a G-protein coupled

receptor, causing the alpha subunit of the G-protein to activate the enzyme adenylyl cyclase. Adenylyl cyclase produces the second messenger cAMP, which activates PKA to phosphorylate CFTR.

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With few exceptions, all the internal and external body surfaces of animals, such as the skin, stomach, and intestines, are covered with a layer of epithelial cells called an epithelium. Many epithelial cells transport ions or small molecules from one side to the other of the epithelium.

Those lining the stomach, for instance, secrete hydrochloric acid into the stomach lumen, which after a meal becomes pH 1, while those lining the small intestine transport products of digestion (e.g., glucose and amino acids) into the blood. All epithelial cells in a sheet are interconnected by several

types of specialized regions of the plasma membrane called cell junctions. These impart strength and rigidity to the tissue and prevent water-soluble material on one side of the sheet (as in the intestinal lumen) from moving across to the other side. In this section we first describe the polarized nature of epithelia and

how different combinations of membrane proteins enable epithelial cells to carry out their transport or secretory functions. Then we discuss the structure and function of the junctions that interconnect epithelial cells.

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“Life laughs at you when you are unhappy... Life smiles at you when you are happy... Life salutes you when you make others happy…”

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