Membrane transport facilitated diffusion

The resorption process is facilitated by the large inner surface of the intestine, with its brush-border cells. Lipophilic molecules penetrate the plasma membrane of the mucosal cells by simple diffusion, whereas polar molecules require transporters (facilitated diffusion see p. 218). In many cases, carrier-mediated cotransport with Na"" ions can be observed. In this case, the difference in the concentration of the sodium ions (high in the intestinal lumen and low in the mucosal cells) drives the import of nutrients against a concentration gradient (secondary active transport see p. 220). Failure of carrier systems in the gastrointestinal tract can result in diseases. 

Membrane proteins lower the activation energy for transport of polar compounds and ions by providing an alternative path through the bilayer for specific solutes. Proteins that bring about this facilitated diffusion, or passive transport, are not enzymes in the usual sense their substrates are moved from one compartment to another, but are not chemically altered. Membrane proteins that speed the movement of a solute across a membrane by facilitating diffusion are called transporters or permeases. 

Drugs and other substances that pass through biologic membranes usually do so via passive diffusion, active transport, facilitated diffusion, or some special process such as endocytosis (Fig. 2-2). Each of these mechanisms is discussed here. 

The transport proteins involved are intrinsic, that is, they span the membrane. They are solute-speciflc, for example, they have binding sites for the specific molecule or ion that they transport. They also have a defined capacity of how many solutes they can transport. An example of facilitated diffusion is glucose that permeates through cell membranes rather slowly via conventional diffusion because it is not soluble in the membrane. However, glucose passes quickly across a cell membrane via facilitated diffusion. 

For the absorption of carbohydrates, amino acids, and peptides, a variety of transport systems following facilitated diffusion and active mechanisms have been identified on a molecular and functional level. D-Glucose is mainly absorbed via the Na -dependent transporter SGLTl in the brush-border membrane of enterocytes [18-20]. It is transported across the basolateral membrane by facilitated diffusion via the hexose transporter GLUT-2. Besides SGLTl, the Na +-independent transport protein GLUT-5 is localized in the apical enterocyte membrane, recognizing fructose as a substrate [21]. 

Fructose transport is distinct from glucose-galactose transport and requires a specific saturable membrane carrier (facilitated diffusion). 

Many nutrients and a few drugs can pass across the cell membrane by facilitated diffusion. In this case, in addition to the concentration gradient, a membrane protein acts as a carrier to transport a substance from one side of the membrane to the other. Carrier proteins are specitic and only transport molecules that they recognize . Glucose enters many body cells by facilitated diffusion and the process appears to be more efficient than simple diffusion. 

Transport across cell membranes by facilitated diffusion occurs through pores within the permease that have conformations, or shapes, that are complementary to those of the transported molecules. The charge and conformation of the pore define the specificity of the carrier (Figure 18.17). Only molecules that have the correct shape can enter the pore. As a result, the rate of diffusion for any molecule is limited by the number of carrier permease molecules in the membrane that are responsible for the passage of that molecule. 

FACILITATED DIFFUSION Membrane transporters may facilitate diffusion of ions and organic compounds across the plasma membrane this facilitated diffusion does not require energy input. Just as in passive diffusion, the transport of ionized and nonionized compounds across the plasma membrane occurs down their electrochemical potential gradient. Therefore, steady state will be achieved when the electrochemical potentials of the compound on both sides of the membrane become equal. 

All of the transport systems examined thus far are relatively large proteins. Several small molecule toxins produced by microorganisms facilitate ion transport across membranes. Due to their relative simplicity, these molecules, the lonophore antibiotics, represent paradigms of the mobile carrier and pore or charmel models for membrane transport. Mobile carriers are molecules that form complexes with particular ions and diffuse freely across a lipid membrane (Figure 10.38). Pores or channels, on the other hand, adopt a fixed orientation in a membrane, creating a hole that permits the transmembrane movement of ions. These pores or channels may be formed from monomeric or (more often) multimeric structures in the membrane. 

Phloretin is the aglycon of phlorizin and inhibits the facilitated diffusion of glucose catalyzed by GLUT1 or GLUT4. It has been used to terminate the uptake of glucose in timed assays with isolated membranes or reconstituted transporters. 

PLASMA MEMBRANES ARE INVOLVED IN FACILITATED DIFFUSION, ACTIVE TRANSPORT, OTHER PROCESSES... 

Unphosphorylated functioning according to Fig. 5 catalyzes facilitated diffusion of mannitol across the membrane. The same process has been reported for purified II reconstituted in proteoliposomes [70]. The relevance of this activity in terms of transport of mannitol into the bacterial cell is probably low, but it may have important implications for the mechanism by which E-IIs catalyze vectorial phosphorylation. It would indicate that the transmembrane C domain of Il is a mannitol translocating unit which is somehow coupled to the kinase activity of the cytoplasmic domains. We propose that the inwardly oriented binding site which is in contact with the internal water phase (Ecyt Mtl, see Fig. 5) is the site from where mannitol is phosphorylated when transport is coupled to phosphorylation. Meehan-... 

Absorption. No studies were located regarding the mechanism of absorption in humans or animals after inhalation, oral, or dermal exposure to diisopropyl methylphosphonate. Both facilitated transport and diffusion through the lipophilic portions of the membrane could be involved in absorption processes. No data were found regarding lipid solubility or partition coefficients. 

Under certain conditions, the transfer of various molecules across the membrane is relatively easy. The membrane must contain a suitable transport mediator , and the process is then termed facilitated membrane transport . Transport mediators permit the transported hydrophilic substance to overcome the hydrophobic regions in the membrane. For example, the transport of glucose into the red blood cells has an activation energy of only 16 kJ mol-1—close to simple diffusion. 

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