Transport mechanisms across biological membranes

Figure 2. Classification of the major types of transport mechanisms across biological membranes based on function and phylogeny (modified after M. H. Saier, 2000 [44])...

Recognized Transport Mechanisms Across Biological Membranes... 

There are three major points to be stressed. First, the Hquid/ceUular interface may contribute significantly to mass transfer limitations. Second, when mass transfer Hmitations exist the intrinsic biokinetics parameters cannot be determined. In biochemical reactor design, intrinsic parameters are essential to model adequately the system performance. Furthermore, without an understanding of the intrinsic biokinetics, one cannot accurately study transport mechanisms across biological membranes. The determination of passive or active transport across membranes is strongly affected by the extent of the Hquid/ceUular interfacial resistance. 

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... 

Polylactones (for an example, see Fig. 14.4) are synthetic analogues of naturally occurring ionophores such as enniatin (species that transport ions across biological membranes). Molecular mechanics calculations have been used to predict the stability and selectivity with respect to Li+, Na+, and K+ of a series of new polylactones12661. Metal-ligand interactions were again modeled using a combination of van der Waals and electrostatic terms. 

Surfactant Effects on Microbial Membranes and Proteins. Two major factors in the consideration of surfactant toxicity or inhibition of microbial processes are the disruption of cellular membranes b) interaction with lipid structural components and reaction of the surfactant with the enzymes and other proteins essential to the proper functioning of the bacterial cell (61). The basic structural unit of virtually all biological membranes is the phospholipid bilayer (62, 63). Phospholipids are amphiphilic and resemble the simpler nonbiological molecules of commercially available surfactants (i.e., they contain a strongly hydrophilic head group, whereas two hydrocarbon chains constitute their hydrophobic moieties). Phospholipid molecules form micellar double layers. Biological membranes also contain membrane-associated proteins that may be involved in transport mechanisms across cell membranes. 

In methanol, the hybrid system behaves as a reagent and can be used in automated microfluorometers to assay potassium in the range of 0-6 mM in the presence of 500-3000 fold excess of sodium (Na ) with 99% accuracy. The fluorescent chemosensor also serves as a tool for studying rates of transport of across biological membranes. A mechanism based on photo-induced electron transfer explains the observed fluorescence enhancement caused by K binding. 

The first two volumes in the series New Comprehensive Biochemistry appeared in 1981. Volume 1 dealt with membrane structure and Volume 2 with membrane transport. The editors of the last volume (the present editor being one of them) tried to provide an overview of the state of the art of the research in that field. Most of the chapters dealt with kinetic approaches aiming to understand the mechanism of the various types of transport of ions and metabolites across biological membranes. Although these methods have not lost their significance, the development of molecular biological techniques and their application in this field has given to the area of membrane transport such a new dimension that the appearance of a volume in the series New Comprehensive Biochemistry devoted to molecular aspects of membrane proteins is warranted. 

A further type of mediator includes substances with a relatively low molecular weight that characteristically facilitate the transport of ions across biological membranes and their models. These transport mechanisms can be divided into four groups ... 

Coupled transport was the first carrier facilitated process developed, originating in early biological experiments involving natural carriers contained in cell walls. As early as 1890, Pfeffer postulated that the transport in these membranes involved carriers. Perhaps the first coupled transport experiment was performed by Osterhout, who studied the transport of ammonia across algae cell walls [1], A biological explanation of the coupled transport mechanism in liquid membranes is shown in Figure 11.2 [2],... 

Generally, the following mechanisms can be involved in the transport of drags across biological membranes ... 

Many factors including partition characteristics, degree of ionization, molecular size etc. influence the transport of drugs across biological membranes. Permeation of intact mucosa may also involve passive diffusion, intercellular movement, transport through pores or other mechanisms. The objective of the studies reported here was to employ the dog model to investigate these factors in a systematic and experimentally well-controlled fashion. The non-steriodal anti-inflammatory drug, diclofenac sodium, was selected as a test compound in this evaluation process. 

Transport across biological membranes is classified according to the thermodynamics of the process. Passive transport is a thermodynamically downhill process the species move toward the equilibrium. The driving force for the passive transport is the potential difference between the two sides of the membrane. Active transport is a thermodynamically uphill process, it is coupled to a chemical reaction and is driven by it. The following transport mechanisms have been recognized ... 

Zeuthen, T., and Stein, W.D. 2002. Molecular mechanisms of water transport across biological membranes. Int. Rev. Cytol. 215 1—442. 

Research in vitro and in vivo (particularly in microorganisms) has defined four basic mechanisms of transport across biological membranes (5-7) ... 

Apart from these basic rules of thumb, the ability to predict the relationship between molecular structure and transport across biological membranes is limited beyond narrow ranges of known compounds. Confounding factors include inaccurate, incomplete, and/or noncomparable data, and the potential existence of multiple drug transport mechanisms in real biological membranes. In particular, limited QSAR data are available for the specific drug transporters that are considered in the following sections. 

The most suitable driving force in BI is the reduction of the diffusion path that already operates in transport processes across biological bilayers. Consequently, biocatalyst membranes and specially designed bioreactors, such as jet loop and membrane reactors, are available to intensify biochemical reactions. " " Supported biocatalysts are often employed to enhance catalytic activity and stability and to protect enzymes/ microorganisms from mechanical degradation and deactivation.f Immobilization of the cells is one of the techniques employed to improve the productivity of bioreactors. 

I. Mechanism of toxicity. The mechanism of thallium toxicity is not known. It appears to affect a variety of enzyme systems, resulting in generalized cellular poisoning. Thallium metabolism has some similarities to that of potassium, and it may inhibit potassium flux across biological membranes by binding to Na-K ATP transport enzymes. 

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