Biological membranes transport across

TRANSPORT ACROSS BIOLOGICAL MEMBRANES Drug Efflux and Multidrug Resistance Studies 

The problem of MDR has gained increasing importance in recent years, particularly in the fields of tumor therapy and treatment of bacterial and fungal infections. One of the major mechanisms responsible for development of MDR is overexpression of drug efflux pumps. These membrane-boxmd, ATP-driven transport proteins efflux a wide variety of natural product toxins and chemotherapeutic dmgs out of the 

Modulators and inhibitors of multidrug efflux transporters, such as Pgp, are used to reduce or inhibit MDR, which leads to a failure of the chemotherapy of, for example, cancers, epilepsy, bacterial, parasitic, and fungal diseases. Binding and transport of first-, second-, and third-generation modulators and inhibitors of Pgp take into account the properties of the drug (H-bonding potential, dimensions, and pK values) as well as the properties of the membrane. 

Gram-positive lactic acid bacteria possess several MDRs that excrete out of the cell a wide variety of mainly cationic lipophilic cytotoxic compotmds as well as many clinically relevant antibiotics. These MDRs are either proton/drug antiporters belonging to the major facilitator superfamily of secondary transporters or ATP-dependent primary transporters belonging to the ATP-binding cassette superfamily of transport proteins. 

The in vitro-in vivo correlation (IVIVC) is an extremely useful exercise at the preformulation level that determines how scale up and post approval changes or Biowaiver principles would be exploited. Conceptually, IVIVC describes a relationship between the in vitro dissolution/release versus the in vivo absorption. This relationship is an important item of research in the development of drug 

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Trace Element Transport Across Biological Membranes. 485... 

TRACE ELEMENT TRANSPORT ACROSS BIOLOGICAL MEMBRANES... 

Raouf Hamid, M., F. Shmela, and S.A. Metwally. 1985. Influence of capsaicin on drug absorption and transport across biological membranes. J Drug Res Egypt 16 67. 

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). 

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 ... 

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. 

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

Haines, T. H. (1994). Water transport across biological membranes. FEBS Lett. 546 115. 

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. 

Chisty MNA, Bellantone RA, Taft DR, Plakogiannis FM. In vitro evaluation of the release of albuterol sulfate from polymer gels effect of fatty acids on drug transport across biological membranes. Drug Dev Ind Pharm 2002 28(10) 1221—1229. 

Some Features of Solute Active Transport Across Biological Membranes Christopher Walsh 11, 222... 

Most molecules are transported across biological membranes by specific protein carriers known as permeases. When a solute diffuses through a membrane from an area of high concentration to an area of low concentration by passing through a channel within a permease, the process is known as facilitated diffusion. No energy is consumed by facilitated diffusion thus it is another means of passive transport, and the direction of transport depends upon the concentrations of metabolite on each side of the membrane. 

The simplest type of membrane transport is passive diffusion of a substance across the lipid bilayer from the region of higher concentration to that of lower concentration. Many metabolites are transported across biological membranes by permeases that form pores through the membrane. The conformation of the pore is complementary to that of the substrate to be transported. Cells use energy to transport molecules across the plasma membrane against their concentration gradients, a process known as active transport. 

Drug response, whether therapeutic or toxic, is dictated by drug concentration at sites of action located outside the site of drug administration. Thus, tissue distribution can often be a critical determinant of drug action, and is a complex process that involves drug transport across biological membranes into the blood, and distribution to sites of action or storage and eventually to sites of elimination. 

Certain trace metals are available for uptake into organisms from solution only as hydrated ions, whereas others are transported across biological membranes as inorganic complexes. In experiments in which the hydrated species of Cu and Cd were either carefully controlled by organic chelators or determined by means of ion-selective electrodes, the toxicity and bioavailability were correlated with the concentration of hydrated metal ions rather than the total dissolved... 

Polyether antibiotics contain tetrahydrofuran rings. In monensin 11, three tetrahydrofuran rings are linearly connected. The molecule contains 17 asymmetric centres. Stereoselective syntheses for monensin have been elaborated [18]. In nonactin 12, the rings are interconnected in an a,a -orientation via ester groupings. Nonactin is therefore classed as a macrolide antibiotic. Polyethers of the type 11/12 are capable of facilitating ion transport across biological membranes they are, therefore, also known as ionophores. 

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