Transport across membranes kinetics

Kim et al. [35] have studied the kinetics of transport across membranes by measuring the variation in emission intensity of the entrapped fluorophore. 

Other phenomena are interesting from the noise point of view. They related to ion transport across membranes/ " equilibrium and nonequilibrium kinetic systems/ nerve membrane noise, " and membrane current fluctuations from ionic channels (Na channels and K channels in axons) in stationary or nonstationary states.Some of these studies have been described in extended reviews. 

Ionic concentration gradients across membranes serve a variety of functions in cellular activity such as maintainance of resting potential, transmission of nerve impulse, driving cotransport, and secretion or activation of enzymes, hormones and other substances. Thus, studies of the kinetics and mechanism of ion transport across membranes are essential for the understanding of many physiological processes. 

Kinetics and Mechanisms of Action.—A book entitled Kinetics of Enzyme Mechanisms has examined the wide-ranging concepts and methods that are used to obtain information on enzyme mechanisms. It covers the essential ideas behind various kinetic methods, with little mathematical detail, and includes sections on inhibitors, activators, co-operative interactions, and transport across membranes. 

In the second chapter of this book, we shall represent and discuss a few examples of physical or chemical models for biological phenomena like transport across membranes, membrane excitation, control of metabolism, and population dynamic interaction between different species. All these models will be of the type of a reaction kinetic model, i.e., the model processes are chemical reactions and diffusion of molecules or may at least be interpreted like that. Thus, the physical background of the various models is irreversible thermodynamics of reactions and diffusion. 

Figure 7.15 Kinetics of transport across a filter-immobilized artificial membrane (a) desipramine and (b) dihydromethysticin concentrations in acceptor well. [Reprinted from Avdeef, A., in van de Waterbeemd, H. Lennemas, H. Artursson, R (Eds.). Drug Bioavailability. Estimation of Solubility, Permeability, Absorption and Bioavailability. Wiley-VCH Weinheim, 2003 (in press), with permission from Wiley-VCH Verlag GmbH.]...

Note that in the component mass balance the kinetic rate laws relating reaction rate to species concentrations become important and must be specified. As with the total mass balance, the specific form of each term will vary from one mass transfer problem to the next. A complete description of the behavior of a system with n components includes a total mass balance and n - 1 component mass balances, since the total mass balance is the sum of the individual component mass balances. The solution of this set of equations provides relationships between the dependent variables (usually masses or concentrations) and the independent variables (usually time and/or spatial position) in the particular problem. Further manipulation of the results may also be necessary, since the natural dependent variable in the problem is not always of the greatest interest. For example, in describing drug diffusion in polymer membranes, the concentration of the drug within the membrane is the natural dependent variable, while the cumulative mass transported across the membrane is often of greater interest and can be derived from the concentration. 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

Kasianowicz, J., Benz, R. and McLaughlin, S. (1984). The kinetic mechanism by which CCCP (carbonyl cyanide m-chloro-phenyl-hydrazone) transports protons across membranes, J. Membrane Biol., 82, 179-190. 

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... 

By contrast, the kinetics of transport across a biological membrane usually does not exhibit such a linear dependence on AC. Instead, the rate approaches an asymptote at high concentration differences, much as the rate of an enzymatic reaction approaches a maximum rate at high substrate concentrations (fig. 17.24d). This behavior suggests that the transport protein has a specific binding site for the material that it transports. The overall rate of transport is limited by the number of these sites in the membrane, and thus fits an... 

To elucidate the role ofhydrophobic bonding, a detailed study on the kinetics ofin-testinal absorption has been performed on sulfonamides. It was concluded that transport across the microvillus membrane occurs via kinks in the membrane which are pictured as mobile structural defects representing mobile free volumes in the hydrocarbon phase of the membrane and whose diffusion coefficient is fairly fast ( 10-5 cm2/s) [1]. The thermal motion of the hydrocarbon chain leads to the formation of kinks. It was also postulated that a transient association of the drug molecules with proteins on the surface of the microvillus membrane is involved in the formation of the activated complex in the absorption process [1]. 

The transport of some solutes across membranes does not resemble diffusion and suggests a temporary, specific interaction of the solute with some component (protein) of the membrane characterized as carrier, e.g., the small-peptide carrier of the intestinal epithelium. The rate of transport increases in proportion to concentration only when this is small, and it attains a maximal rate that cannot be exceeded even with a large further increase in concentration. The kinetics of carrier-mediated transport is theoretically treated by considering carrier-solute... 

It has been generally assumed that iron is transported across biological membranes in the ferrous form and that ferric iron would have to be reduced before it can be used by the organism. Thus, based on nutritional studies it has long been recognized that Fe(II) is1 more effectively absorbed than Fe(III), and this has been attributed to differences in the thermodynamic and kinetic stability of the complexes and chelates formed by these cations (for review, see Ref. 2). The experimental proof of a transport in the ferrous form has, however, not been given until quite recently in studies of iron transport in isolated mitochondria (23) as well as in enterobacteria (33). In rat liver mitochondria we have found that Fe(III) donated from a metabolically inert water soluble complex of sucrose interacts with the respiratory chain at the level of cytochrome c (and possibly cytochrome a) (23, 32) (Figure 1 B), which has a oxidation-reduction potential of around +250 mV (34) and is localized to the outer phase of the mitochondrial inner membrane (35). 

Ion transfer across phospholipid monolayers at liquid-liquid interfaces has been studied with the aim of elucidating the mechanism and kinetics of ion transport across a bilayer lipid membrane (BLM). The main advantage of using these systems is in the possibility of controlling the interfacial potential difference, which in the case of the BLM has to be inferred indirectly [141]. 

Laboratory studies have suggested that there are three modes of transport for silicic acid (reviewed by Martin-Jezequel et al., 2000) first, silicic acid may be rapidly transported across the cell membrane, following surge uptake kinetics. This occurs primarily in Si-starved cells with cell quotas (Droop, 1968, 1973) near minimal values. Second, sdicic acid uptake can be controlled internally, presumably due to regulation ofsihcaprecipitation and deposition (e.g., Hildebrand et al., 1997). Third, silicic acid uptake may be controlled externally due to substrate hmitation. 

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