Cell membrane Carrier mechanism

Reabsorbed bile acids are transported back to the liver in the portal blood bound to albumin, where they are taken up by parenchymal cells for excretion into bile. The uptake process has been studied in isolated rat hepato-cytes (S17), the perfused rat liver (Rl), and cultured rat hepatocytes (V5), and a bile acid receptor protein has been partially characterized in liver cell membrane preparations (Al). Taken together, these studies suggest that uptake is via a coupled membrane carrier mechanism, whereby bile salt anions are cotransported with sodium cations across the liver cell sinusoidal membrane. Although the majority of bile acids are extracted from portal blood by the liver, a small fraction (less than 1% of the total bile salt pool)... 

Cell membranes are lipophilic and designed to be barriers against large anionic molecules, although there is a natural mechanism for intercellular transport of anionic oligonucleotides. In order to enhance membrane transport, antisense oligonucleotides are frequentiy modified by covalent attachment of carrier molecules or lipophilic groups. 

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 the adequacy of lipid bilayer membranes as models for the basic structural motif and hence for the ion transport barrier of biological membranes, studies of channel and carrier ion transport mechanisms across such membranes become of central relevance to transport across cell membranes. The fundamental principles derived from these studies, however, have generality beyond the specific model systems. As noted above and as will be treated below, it is found that selective transport... 

Spin trapping methods were also used to show that when carotenoid-P-cyclodextrin 1 1 inclusion complex is formed (Polyakov et al. 2004), cyclodextrin does not prevent the reaction of carotenoids with Fe3+ ions but does reduce their scavenging rate toward OOH radicals. This implies that different sites of the carotenoid interact with free radicals and the Fe3+ ions. Presumably, the OOH radical attacks only the cyclohexene ring of the carotenoid. This indicates that the torus-shaped cyclodextrins, Scheme 9.6, protects the incorporated carotenoids from reactive oxygen species. Since cyclodextrins are widely used as carriers and stabilizers of dietary carotenoids, this demonstrates a mechanism for their safe delivery to the cell membrane before reaction with oxygen species occurs. 

Hepatocytes make up 60-70% of the total number of liver cells. They have a well-organized intracellular structure with huge numbers of cell organelles to maintain the high metabolic profile. At the apical side or canalicular membrane the cell is specialized for the secretion of bile components. There are several ATP-dependent transport carriers located on this side of the membrane, which transport bile salts, lipids and xenobiotics into the canaliculus. On the sinusoidal side, the cells specialize in uptake and secretion of a wide variety of components. To increase the surface of the membrane for this exchange with the bloodstream, the sinusoidal domain of the membrane is equipped with irregular microvilli. The microvilli are embedded into the fluid and matrix components of the space of Disse and are in close contact with the sinusoidal blood because of the discontinuous and fenestrated SECs. To facilitate its metabolic functions numerous membrane transport mechanisms and receptors are situated in the membrane. 

Although such receptors often provide mechanisms for internalization followed by intracellular transport to compartments where degradation takes place, the rates of these processes can be markedly different in various cell types. In some cases only external binding occurs and consequently, the microclimate of the cell membrane at which local release of the drug from the carrier takes place, should provide sufficient driving force to ensure uptake of the drug into the target cell. 

Ions and small molecules may be transported across cell membranes or lipid bilayers by artificial methods that employ either a carrier or channel mechanism. The former mechanism is worthy of brief investigation as it has several ramifications in the design of selectivity filters in artificial transmembrane channels. To date there are few examples where transmembrane studies have been carried out on artificial transporters. The channel mechanism is much more amenable to analysis by traditional biological techniques, such as planar bilayer and patch clamp methods, so perhaps it is not surprising that more work has been done to model transmembrane channels. 

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. 

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