Transport across membranes saturation

Carrier-mediated transport across membranes adds additional complexity to the system and, thus, to the model. For even the simplest transporter, the concentration of the transporter and its affinity for the substrate must be known before it can be modeled. Also, active transport is inherently a saturable process. Thus, to analyze the dynamics of tracer-labeled substrate, the model must account for both labeled and unlabeled substrate as the transport dynamics will depend on total substrate concentration. 

The simplest practicable approach considers the membrane as a continuous, nonporous phase in which water of hydration is dissolved.In such a scenario, which is based on concentrated solution theory, the sole thermodynamic variable for specifying the local state of the membrane is the water activity the relevant mechanism of water back-transport is diffusion in an activity gradient. However, pure diffusion models provide an incomplete description of the membrane response to changing external operation conditions, as explained in Section 6.6.2. They cannot predict the net water flux across a saturated membrane that results from applying a difference in total gas pressures between cathodic and anodic gas compartments. 

Consider the oxidation of palmitoleate. This Cjg unsaturated fatty acid, which has one double bond between C-9 and C-10, is activated and transported across the inner mitochondrial membrane in the same way as saturated fatty acids. Palmitoleoyl CoA then undergoes three cycles of degradation, which are carried out by the same enzymes as in the oxidation of saturated fatty acids. However, the cis-A 3-enoyl CoA formed in the third round is not a substrate for acyl CoA dehydrogenase. The presence of a double bond between C-3 and C-4 prevents the formation of another double bond between C-2 and C-3. This impasse is resolved by a new reaction that shifts the position and configuration of the cis-A double bond. An isomerase converts this double bond into a trans- A double bond. The subsequent reactions are those of the saturated fatty acid oxidation pathway, in which the trans- A 2-enoyl CoA is a regular substrate. 

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). 

Facilitated diffusion is very similar to passive diffusion with the difference that transfer across membranes is assisted by the participation of carrier proteins embedded in the membrane bilayer. Again, the direction of passage will be from the side of the membrane with high concentration of a chemical to the side with low concentration this also occurs without energy expenditure by the cell. Such a process is somewhat specific in the sense that it applies to molecules that are able to bind to a carrier protein. Absorption of nutrients such as glucose and amino acids across the epithelial membrane of the gastrointestinal tract occurs by facilitated diffusion. Since a finite number of carriers are available for transport, the process is saturable at high concentrations of the transported molecules and competition for transport may occur between molecules of similar structure. 

Active transport requires a specialized carrier molecule, a protein, and the expenditure of cellular energy transfer across membranes can therefore occur against a concentration gradient. The carrier system is selective for certain structural features of chemicals, namely their ionized state, whether anionic, cationic, or neutral. Recent advances in the understanding of active transport have led to the characterization of several families of carriers. Such carrier systems are saturable. In addition, molecules with similar structural features may compete for transport by a given carrier. 

Protein-catalyzed transport of a solute across a membrane occurs much faster than passive diffusion, exhibits a Knax when the limited number of transporter molecules are saturated with substrate, and is highly specific for substrate (see Figure 7-3). 

Fig. 10.10. Saturation kinetics of transporter proteins. When a compound must bind to a protein to be transported across a membrane, the velocity of transport depends on the amount of compound bound. It reaches a maximum rate when the compound s concentration is raised so high that aU of the transporter binding sites are occupied. The curve is a rectangular hyperbola that approaches at infinite substrate concentration, identical to that of Michaelis-Menten enzymes. The K , of transport is the concentration of compound required for /z In contrast, simple diffusion of a compound does not require its binding to a protein, and the rate of transport increases linearly with increasing concentration of the compound.

Facilitated transport proteins, such as the glucose transporter, are present in the cell membrane in limited number. As the concentration of the solute increases at the external membrane surface, the transporter binding sites become saturated, and the net rate of solute transport across the membrane approaches a maximal value (Figure 5.11). The rate of transport via the facilitated transport mechanism can be analyzed by considering binding of the transported solute (S) to the transmembrane carrier protein (Cp) to form a carrier-solute complex (S-Cp) ... 

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