Transport across membranes carrier mediated

In Section 3.2 we introduced the basic processes of advection, diffusion, and drift, by which material is transported in biophysical systems. In this chapter we focus on a specialized class of transport transport across biological membranes. Transport of a substance across a membrane may be driven by passive permeation, as described by Equation (3.60), or it may be facilitated by a carrier protein or transporter that is embedded in the membrane. Thus transport of substances across membranes mediated by transporters is termed carrier-mediated transport. The most basic way to think about carrier proteins or transporters is as enzymes that catalyze reactions that involve transport. 

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. 

Both secondary active transport and positive cooperativity effects enhance carrier-mediated solute flux, in contrast to negative cooperativity and inhibition phenomena, which depress this flux. Most secondary active transport in intestinal epithelia is driven by transmembrane ion gradients in which an inorganic cation is cotransported with the solute (usually a nutrient or inorganic anion). Carriers which translocate more than one solute species in the same direction across the membrane are referred to as cotransporters. Carriers which translocate different solutes in opposite directions across the membrane are called countertransporters or exchangers (Figs. 10 and 11). 

The coupled processes described by Eqs. (8), (14), (17), and (22) can be added in (20) as parallel solute transport pathways across the membrane. The phenomenological coefficients (Ly) describe the membrane permeability by these pathways [potential-dependent, Eq. (8) via membrane lipid partition and diffusion, Eq. (14) carrier-mediated, Eq. (17) and convectively coupled, Eq. (22)]. These pathways define parallel resistances through the intestinal barrier in series with precellular resistances to solute transport. 

Although the absence of paracellular transport across the BBB impedes the entry of small hydrophilic compounds into the brain, low-molecular-weight lipophilic substances may pass through the endothelial cell membranes and cytosol by passive diffusion [7]. While this physical barrier cannot protect the brain against chemicals, the metabolic barrier formed by the enzymes from the endothelial cell cytosol may transform these chemicals. Compounds transported through the BBB by carrier-mediated systems may also be metabolized. Thus, l-DOPA is transported through the BBB and then decarboxylated to dopamine by the aromatic amino acid decarboxylase [7]. 

Substances can be transported across epithelial membranes by simple passive diffusion, carrier-mediated diffusion, and active transport, in addition to other specialized mechanisms, including endocytosis. 

This refers to the transport across the epithelial cells, which can occur by passive diffusion, carrier-mediated transport, and/or endocytic processes (e.g., transcytosis). Traditionally, the transcellular route of nasal mucosa has been simply viewed as primarily crossing the lipoidal barrier, in which the absorption of a drug is determined by the magnitude of its partition coefficient and molecular size. However, several investigators have reported the lack of linear correlation between penetrant lipophilicity and permeability [9], which implies that cell membranes of nasal epithelium cannot be regarded as a simple lipoidal barrier. Recently, compounds whose transport could not be fully explained by passive simple diffusion have been investigated to test if they could be utilized as specific substrates for various transporters which have been identified in the... 

Transport across the cell membrane may occur via different routes. Some of these transport processes are energy dependent and therefore termed active others are independent from energy, thus passive. Passive transport phenomena, for example, transcellular transport, are triggered by external driving forces, such as concentration differences, and do not require metabolic activity. However, generally, they are restricted to small lipophilic compounds. In contrast, active transport phenomena, such as active carrier-mediated transport or vesicular pathways, take course independent from external driving... 

Carrier-mediated passage of a molecular entity across a membrane (or other barrier). Facilitated transport follows saturation kinetics ie, the rate of transport at elevated concentrations of the transportable substrate reaches a maximum that reflects the concentration of carriers/transporters. In this respect, the kinetics resemble the Michaelis-Menten behavior of enzyme-catalyzed reactions. Facilitated diffusion systems are often stereo-specific, and they are subject to competitive inhibition. Facilitated transport systems are also distinguished from active transport systems which work against a concentration barrier and require a source of free energy. Simple diffusion often occurs in parallel to facilitated diffusion, and one must correct facilitated transport for the basal rate. This is usually evident when a plot of transport rate versus substrate concentration reaches a limiting nonzero rate at saturating substrate While the term passive transport has been used synonymously with facilitated transport, others have suggested that this term may be confused with or mistaken for simple diffusion. See Membrane Transport Kinetics... 

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