Cell membranes active transport

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... 

During the process of nutrient assimilation, DIN is first actively transported across the cell membrane. This transport is mediated by species-specific enzymes called permeases that are present in the cell membrane. Once the inorganic nitrogen has crossed the cell membrane, it can participate in anabolic reactions. For example, ammonium helps build amino acids by first reacting with a-ketoglutaric acid to generate glutamic acid ... 

Mallinger AG, Hanin 1, Himmeloch JM, et al Stimulation of cell membrane sodium transport activity by lithium possible relationship to therapeutic action. Psychiatry Res 22 49-59, 1987... 

Cells drive active transport in a variety of ways. The plasma-membrane Na+-K+ pump of animal cells (a) and the plasma-membrane H+ pump of anaerobic bacteria (b) are driven by the hydrolysis of ATP. Eukaryotic cells couple the uptake of neutral amino acids to the inward flow of Na+ (c). Uptake of /3-gal actosidcs by some bacteria is coupled to inward flow of protons (d). Electron-transfer reactions drive proton extrusion from mitochondria and aerobic bacteria (e). In halophilic bacteria, bacteriorhodopsin uses the energy of sunlight to pump protons (/). E. coli and some other bacteria phosphorylate glucose as it moves into the cell and thus couple the transport to hydrolysis of phosphoenolpyruvate (g). 

Two stationary states in the coupled processes can be identified as the level flow where A = 0, and the static head where J, = 0. Examples of the static head are open-circuited fuel cells and active transport in a cell membrane, while examples of the level flow are short-circuited fuel cells and salt and water transport in kidneys. 

Controlling Material Transport - Ion Channels Ion channels maintain two different ion compositions outside and inside a cell via active transport. The immobilization of appropriately designed molecules in a lipid bilayer membrane leads to the formation of artificial ion channels. 

Na" "/K+ ATPase pump - active transport mechanism in cell membranes for transport of sodium and potassium ions... 

If osmosis and simple diffusion were the only mechanisms for transporting water and ions across cell membranes, these concentration differences would not occur. One positive ion would be just as good as any other. However, the situation is more complex than this. Large protein molecules embedded in cell membranes actively pump sodium ions to the outside of the cell and potassium ions into the cell. This is termed active transport because cellular energy must be expended to transport those ions. Proper cell function in the regulation of muscles and the nervous system depends on the sodium ion/potassium ion ratio inside and outside of the cell. 

F. 10.12. Active transport by Na, K -ATPase. Three sodium ions bind to the transporter protein on the cytoplasmic side of the membrane. When ATP is hydrolyzed to ADP, the carrier protein is phosphorylated and undergoes a change in conformation that causes the sodium ions to be released into the extracellular fluid. Two potassium ions then bind on the extracellular side. Dephosphorylation of the carrier protein produces another conformational change, and the potassium ions are released on the inside of the cell membrane. The transporter protein then resumes its original conformation, ready to bind more sodium ions. 

A permease (carrier [16]) is assumed to have the characteristics of an enzyme and thus exhibits stereospecificity for the transported solute. It can traverse the cell membrane, thus transporting the solute from the outside to the inside of the cell, and both influx and efflux of solute occur. The transport will usually exhibit saturation (Michaelis-Menten) kinetics. Enzymes involved in facilitated diffusion or active transport (i.e. permeases and molecules responsible for the intracellular modification of the transported solute) may be either constitutive or inducible. This means that the system may be present at all times (constitutive) or developed by the cell only in the presence of the transported solute (inducible). Clearly for induction to occur some of the solute must enter the cell either by way of a small (constitutive) amount of the transport system or by another means (e.g. diffusion). When the inducer concentration falls to zero or below a critical level, the transport system fails to operate thus a degree of control on the entry of the inducer is exercised. The presence of glucose in the medium may prevent the synthesis of the transport system (catabolite repression) thereby enabling glucose to be... 

The yeast cell membrane may be envisioned as a selectively permeable barrier that serves a vital role in the organism s ability to maintain osmotic balance and regulate transport of essential nutrients into and metabolites (including ethanol) out of the cell. Ethanol is soluble in both aqueous and lipid phases of the cell membrane and its formation and passive effusion eventually interferes with structure and function of the membrane. Particularly important in this regard are the cell-membrane-associated transport enzymes such as those responsible for uptake of sugars and critical amino acids. During active fermentation at warm temperatures, ethanol accumulates intracellularly faster than it can be eliminated from the cell. This situation worsens as extracellular concentrations increase. Thus, temperature- and ethanol-directed inhibition is likely the result of the time delay arising from passive diffusion coupled with impaired membrane function. 

Amino acids are rapidly absorbed in the intestine. The intestinal wall is lined with specialized absorptive cells whose primary function is the transport of nutrients from the lumen of the gut into the portal circulation. These cells contain active transport systems for both sugars and amino acids in the brush border membrane. 

Fig. 1 Major pathways in the young rat s fat cell for uptake of extracellular FFA or triglyceride, for uptake and metabolism of glucose, and for mobilization of stored triglyceride. Circles indicate major points of hormonal control transport of glucose across the cell membrane, activity of the hormone-sensitive lipase which hydrolyzes intracellular stored triglyceride, and activity of the lipoprotein lipase which hydrolyzes extracellular triglyceride.

They essentially show a dual mechanism of action firstly, the antibiotic penetrates cells by active transport, altering the permeability of the membrane (which explains the synergy with P-lactams). Secondly, once it is present into the cell cytoplasm, it binds to the 30 S ribosomal subunit inhibiting protein synthesis. 

Phospholipids. Phospholipids, components of every cell membrane, are active determinants of membrane permeabiUty. They are sources of energy, components of certain enzyme systems, and involved in Hpid transport in plasma. Because of their polar nature, phosphoUpids can act as emulsifying agents (42). The stmcture of most phosphoUpids resembles that of triglycerides except that one fatty acid radical has been replaced by a radical derived from phosphoric acid and a nitrogen base, eg, choline or serine. 

Active Transport. Maintenance of the appropriate concentrations of K" and Na" in the intra- and extracellular fluids involves active transport, ie, a process requiring energy (53). Sodium ion in the extracellular fluid (0.136—0.145 AfNa" ) diffuses passively and continuously into the intracellular fluid (<0.01 M Na" ) and must be removed. This sodium ion is pumped from the intracellular to the extracellular fluid, while K" is pumped from the extracellular (ca 0.004 M K" ) to the intracellular fluid (ca 0.14 M K" ) (53—55). The energy for these processes is provided by hydrolysis of adenosine triphosphate (ATP) and requires the enzyme Na" -K" ATPase, a membrane-bound enzyme which is widely distributed in the body. In some cells, eg, brain and kidney, 60—70 wt % of the ATP is used to maintain the required Na" -K" distribution. 

Biochemically, most quaternary ammonium compounds function as receptor-specific mediators. Because of their hydrophilic nature, small molecule quaternaries caimot penetrate the alkyl region of bdayer membranes and must activate receptors located at the cell surface. Quaternary ammonium compounds also function biochemically as messengers, which are generated at the inner surface of a plasma membrane or in a cytoplasm in response to a signal. They may also be transferred through the membrane by an active transport system. 

Materials may be absorbed by a variety of mechanisms. Depending on the nature of the material and the site of absorption, there may be passive diffusion, filtration processes, faciHtated diffusion, active transport and the formation of microvesicles for the cell membrane (pinocytosis) (61). EoUowing absorption, materials are transported in the circulation either free or bound to constituents such as plasma proteins or blood cells. The degree of binding of the absorbed material may influence the availabiHty of the material to tissue, or limit its elimination from the body (excretion). After passing from plasma to tissues, materials may have a variety of effects and fates, including no effect on the tissue, production of injury, biochemical conversion (metaboli2ed or biotransformed), or excretion (eg, from liver and kidney). 

The influx of Ca(Il) across the presynaptic membrane is essential for nerve signal transmission involving excitation by acetylcholine (26). Calcium is important in transducing regulatory signals across many membranes and is an important secondary messenger hormone. The increase in intracellular Ca(Il) levels can result from either active transport of Ca(Il) across the membrane via an import channel or by release of Ca(Il) from reticulum stores within the cell. More than 30 different proteins have been linked to regulation by the calcium complex with calmoduhn (27,28). 

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