Carrier mechanism

This review addresses the issues of the chemical and physical processes whereby inorganic anions and cations are selectively retained by or passed through cell membranes. The channel and carrier mechanisms of membranes permeation are treated by means of model systems. The models are the planar lipid bilayer for the cell membrane, Gramicidin for the channel mechanism, and Valinomycin for the carrier mechanism. 

With respect to the carrier mechanism, the phenomenology of the carrier transport of ions is discussed in terms of the criteria and kinetic scheme for the carrier mechanism the molecular structure of the Valinomycin-potassium ion complex is considered in terms of the polar core wherein the ion resides and comparison is made to the Enniatin B complexation of ions it is seen again that anion vs cation selectivity is the result of chemical structure and conformation lipid proximity and polar component of the polar core are discussed relative to monovalent vs multivalent cation selectivity and the dramatic monovalent cation selectivity of Valinomycin is demonstrated to be the result of the conformational energetics of forming polar cores of sizes suitable for different sized monovalent cations. 

Fig. 17. Membrane current, Xq, of a dioleoyllecithin membrane, A. as a function of Valinomycin concentration at 1 M KC1 and B. as a function of KC1 concentration at 10"7 M Valinomycin. The linearity and slope of one indicates a carrier mechanism with a 1 1 carrier to cation stoichiometry. Reproduced with permission from Ref.811...

Fig. 18. Kinetic scheme for the Valinomycin carrier mechanism of transport. Reproduced with permission from Ref. 87)...

Since many essential nutrients (e.g., monosaccharides, amino acids, and vitamins) are water-soluble, they have low oil/water partition coefficients, which would suggest poor absorption from the GIT. However, to ensure adequate uptake of these materials from food, the intestine has developed specialized absorption mechanisms that depend on membrane participation and require the compound to have a specific chemical structure. Since these processes are discussed in Chapter 4, we will not dwell on them here. This carrier transport mechanism is illustrated in Fig. 9C. Absorption by a specialized carrier mechanism (from the rat intestine) has been shown to exist for several agents used in cancer chemotherapy (5-fluorouracil and 5-bromouracil) [37,38], which may be considered false nutrients in that their chemical structures are very similar to essential nutrients for which the intestine has a specialized transport mechanism. It would be instructive to examine some studies concerned with riboflavin and ascorbic acid absorption in humans, as these illustrate how one may treat urine data to explore the mechanism of absorption. If a compound is... 

Structure and physiology of the kidney glomerular filtration tubular activity selective reabsorption and secretion, often using specific carrier mechanisms carbonic anhydrase and acid-base balance. The kidney also produces, and is sensitive to, hormones actions of the hormones ADH, aldosterone and PTH the kidney as a secretory organ erythropoietin, the renin-angiotensin system vitamin D3. 

Certain factors determine distribution of drugs to the central nervous system. An important determinant is the drug s molecular size, because cerebral capillaries have tight junctions and only the smallest molecules can pass through unless there is a specific carrier mechanism. However, drugs that are highly lipid soluble may pass through the brain s perme-... 

A carrier mechanism was excluded for these molecules when ion-transport activity was undiminished in membranes in the gel state. The transport rates... 

Five membranes (thickness, 40 /am) were stacked and the concentration of ligand and cation in each membrane was measured before and immediately after the transport experiment as well as 5 days after restacking the membranes. Since a concentration gradient of valinomycin developed (Fig. 11, f = 3hr), which decayed almost completely after a relaxation period (Fig. 11, l = 5 days), the a-phenylethylammonium cation had obviously been transported by a carrier mechanism. During the transport process a cation profile built up (Fig. 12, t = 3 hr) that had the same trend as the ligand profile. This cation gradient disappeared after some time (Fig. 12, t = 5 days). 

Is it possible to synthesize ionophores specific for anions These molecules would be of great importance in practical applications, especially in medicine. If they could be made stereospecific they could, in addition, offer new insights into enzyme and carrier mechanisms since they can be regarded as primitive models of such molecules. 

I assume, the membranes you are referring to are classical ion exchange membranes, the behavior of which is dictated to a large degree by charged groupings of the membrane material. The ion transport mechanism in such membranes is clearly not a carrier mechanism. 

I disagree with Dr. Thomas that there are no known biological channels or carriers. I know of at least one example of a clearly demonstrated channel. This is the acetylcholine activated channel in denervated muscle demonstrated so elegantly by Neher and Sackmann (Nature, 260, 119, 1976), who resolved unit conductance jumps that are far too large to be accounted for by a carrier mechanism. A less unambiguously demonstrated example of channels are the Na+ and K+ channels of nerve, which both by noise analysis and pharmacological evidence imply the movement of about 1000 times as many ions in a unit of time as is reasonable for any diffusive carrier mechanism across the entire membrane. 

The selectivity ratio K+ Na+ at 25 °C is of the order 104 1 whereas at 0°C it is reduced to only 2 1.543 This dramatic decrease has been interpreted as indirect evidence for the possible role of (137) as a carrier in membranes as, if it provided a pore mechanism, this would be unimpaired by freezing. In a carrier mechanism which necessarily involves a mobile ligand to effect incorporation and transfer of the metal freezing would cause a loss of mobility and so impair the mechanism. The high K+ selectivity of (137) has led to its employment in ion-selective electrodes.543... 

G.M. Shean and K. Sollner, Carrier Mechanisms in the Movement of Ions Across Porous and Liquid Ion Exchanger Membranes, Ann. N.Y. Acad. Sci. 137, 759 (1966). 

Both processes exhibit classical saturation kinetics, since there are only a finite number of carrier molecules. Thus unlike passive absorption (paracellular or transcellular), where the rate of transport is directly proportional to the drug concentration (Figure 1.5, A), carrier-mediated transport is only proportional to the drag concentration at low concentrations of drug. At higher concentrations, the carrier mechanism becomes saturated and the rate of absorption remains constant (Figure 1.5, B). 

Other processes that lead to nonlinear compartmental models are processes dealing with transport of materials across cell membranes that represent the transfers between compartments. The amounts of various metabolites in the extracellular and intracellular spaces separated by membranes may be sufficiently distinct kinetically to act like compartments. It should be mentioned here that Michaelis-Menten kinetics also apply to the transfer of many solutes across cell membranes. This transfer is called facilitated diffusion or in some cases active transport (cf. Chapter 2). In facilitated diffusion, the substrate combines with a membrane component called a carrier to form a carrier-substrate complex. The carrier-substrate complex undergoes a change in conformation that allows dissociation and release of the unchanged substrate on the opposite side of the membrane. In active transport processes not only is there a carrier to facilitate crossing of the membrane, but the carrier mechanism is somehow coupled to energy dissipation so as to move the transported material up its concentration gradient. 

The individual reactions affected by iron stress can be considered as regulated biochemical pathways, although regulation by iron is not understood. The mechanism of iron absorption and transport involves the release of hydrogen ions by the root, which lowers the pH of the root zone. This favors Fe3+ solubility and reduction of Fe3 to Fe2+. Reductants are released by roots or accumulate in roots of plants that are under iron stress. These "reductants, along with Fe3+ reduction by the root, reduce Fe3+ to Fe2+, and Fe2+ can enter the root. Ferrous iron has been detected throughout the protoxylem of the young lateral roots. The Fe2+ is probably kept reduced by the reductant in the root, and it may or may not have entered the root by a carrier mechanism. The root-absorbed Fe2+ is believed to be oxidized to Fe3, chelated by citrate, and transported in the metaxylem to the tops of the plant for use. We assume Fe2+ is oxidized as it enters the metaxylem because there is no measureable Fe2+ there (13), and Fe3+ citrate is transported in the xylem exudate (30, 31,32). 

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