Facilitated transport mechanisms

Anandamide is inactivated in two steps, first by transport inside the cell and subsequently by intracellular enzymatic hydrolysis. The transport of anandamide inside the cell is a carrier-mediated activity, having been shown to be a saturable, time- and temperature-dependent process that involves some protein with high affinity and specificity for anandamide (Beltramo, 1997). This transport process, unlike that of classical neurotransmitters, is Na+-independent and driven only by the concentration gradient of anandamide (Piomelli, 1998). Although the anandamide transporter protein has not been cloned yet, its well characterized activity is known to be inhibited by specific transporter inhibitors. Reuptake of 2-AG is probably mediated by the same facilitating mechanism (Di Marzo, 1999a,b Piomelli, 1999). 

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. 

Kahn BB (1992), Facilitative glucose transporters. Regulatory mechanisms and deregulation in diabetes, J. Clin. Invest. 89 1367-1374. 

Another technique to expedite the transport of the volatile components from the molten polymer is to increase the number and rate of bubbles formed [14], Techniques that have been used to increase the number of bubbles and their rate of formation (nucleation) are the addition of chemical nucleating agents [15] and ultrasound [16]. Nucleation of bubbles in the molten polymer can help expedite the achievement of equilibrium in conventional falling strand devolatilizers. However, this facilitation mechanism cannot get below equilibrium and thus has minimal value. 

In carrier-mediated transport studies, two terms are used, namely, facilitated transport and coupled transport. Facilitated transport is generally referred to as the case where the transport mechanism is independent of any other ion, while in case of coupled transport the transport rate of a particular ion is dependent on the concentration of another ion. The mechanism of facilitated transport is shown in Figure 31.3 a, while those of the two different types of coupled transport (cotransport and counter-transport) are schematically explained in Figure 31.3b and 31.3c. In case of cotransport, the metal ion is transferred along with a counter-anion, while simultaneous transport of another ion from receiver phase to source phase occurs in case of counter-transport. 

Experimentally, it has been observed that many substances are transported across plasma membranes by more complicated mechanisms. Although no energy is expended by the cell and the net flux is still determined by the electrochemical potential, some substances are transported at a rate faster than predicted by their permeability coefficients. The transport of these substances is characterized by a saturable kinetic mechanism the rate of transport is not linearly proportional to the concentration gradient. A facilitated mechanism has been proposed for these systems. Substances interact and bind with cellular proteins, which facilitate transport across the membrane by forming a channel or carrier. The two basic models of facilitated diffusion, a charmel or a carrier, can be experimentally distinguished (1,2). 

The basic mechanisms involved in solute transport across the plasma membrane include passive diffusion, facilitated diffusion, and active transport. Active transport can be further subdivided into primary and secondary active transport. These mechanisms are depicted in Figure 2-4. 

Fig. 10.9. Facilitative transport. Although the molecule being transported must bind to the protein transporter, the mechanism is passive diffusion, and the molecule moves from a region of high concentration to one of low concentration. Passive refers to the lack of an energy requirement for the transport.

Far higher selectivities can be obtained by adding a carrier molecule to the liquid (membrane) which has a high affinity for one of the solutes in phase 1. The carrier accelerates the transport of this specific component. This type of transport is called carrier mediated transport or facilitated transport. The mechanism of facilitated transport can be demonstrated by the simple experiment dqpicted schematically in figure VI > 32. 

Kozlowski et al. [18] obtained the p CD polymers, which were prepared by crosslinking of 3-CD with 2-(l-docosenyl)-succinic anhydride derivatives in anhydrous N,N-dimethylformamide in the presence of NaH. It was established that the elongation of the hydrocarbon chain in the obtained 3-CD polymer in the reaction with 2-(l-docosenyl)-succinic anhydride results in the selectivity for Pb(ll) ions in the ion transport with the use of this ion carrier. At room temperature the dimmer was obtained, while at 100°C the polymers of 34kD and 13.5 kD fractions were received. The transport kinetics investigation on dependence of the carrier and Pb(II) concentrations have shown that the transport by the dimmer proceeded by the facilitated mechanism, typical for liquid membranes. The polymer however, has shown a linear increase of the transport flux in dependence on metal concentration in the source phase, this fact indicating that the polymer form of 3-CD prefers probably the fixed site mechanism of transport. PIMs containing dimmer and polymer of CD, in the transport of Zn(II), Cu(II) and Pb(Il) showed selectivity orders Pb(Il) Cu(II), Zn([]), and Pb(II) Cu(II) > Zn(II), respectively. The high selectivity factor for Pb(II)/Cu(II) equal to 163 for the dimmer was achieved (Table 1). 

Chaperones bind to exposed hydrophobic surfaces of polypeptide substrates, and through either ATP-dependent or ATP-independent mechanisms facilitate the folding/assembly, intracellular transport, degradation, and activity of polypeptides. 

However, despite this lack of a basic understanding of the electrochemistry of these materials, much progress has been made in characterizing polymerization mechanisms, degradation processes, transport properties, and the mediation of the electrochemistry of species in solution. These advances have facilitated the development of numerous applications of conducting polymers, and so it can be anticipated that interest in their electrochemistry will remain high. 

In PBPK models tissue blood perfusion and tissue composition can be characterized independently of the drug thus such a model can be created once and reused for many different drugs. Furthermore, because physical laws (mass conservation, diffusion, or facilitated transport mechanisms) are incor-... 

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