Molecules, transport across membranes

All of the transport systems examined thus far are relatively large proteins. Several small molecule toxins produced by microorganisms facilitate ion transport across membranes. Due to their relative simplicity, these molecules, the lonophore antibiotics, represent paradigms of the mobile carrier and pore or charmel models for membrane transport. Mobile carriers are molecules that form complexes with particular ions and diffuse freely across a lipid membrane (Figure 10.38). Pores or channels, on the other hand, adopt a fixed orientation in a membrane, creating a hole that permits the transmembrane movement of ions. These pores or channels may be formed from monomeric or (more often) multimeric structures in the membrane. 

The partition coefficient is needed to determine the moles lost to the membrane, VM CM(t). If ionizable compounds are considered, then one must decide on the types of partition coefficient to use -Kp (true pH-independent partition coefficient) or Kd (pH-dependent apparent partition coefficient). If the permeability assay is based on the measurement of the total concentrations, Cn(t) and CA(t), summed over all charge-state forms of the molecule, and only the uncharged molecules transport across the membrane to an appreciable extent, it is necessary to consider the apparent partition (distribution) coefficient, Kd, in order to explain the pH dependence of permeability. 

An exciting area in inclusion chemistry is the design and synthesis of molecules which could behave as ion channels. Future developments in this field offer the potential for developing new synthetic antibiotic molecules, model systems for investigating transport across membranes, and ion channels specific for particular ions. Such studies are so far only in their infancy. 

Movement of Ions and Molecules Across Membranes Transport Across Membranes The Nernst Equation... 

Phagocytosis is an important mechanism for the organism to rid itself of bacteria and pathogenic material, as well as cell debris and remnants of apoptosis. However, it can also provide a route for the uptake of pollutant particulate material. It is seen to be especially important in the incorporation of airborne particulate material, which often has serious health consequences (see Section 6.4). In terrestrial invertebrates, food is obtained either from particulate matter in the soil or from molecules dissolved in interstitial water. Most of these organisms have extracellular digestion, with nutrients and foreign material being absorbed by one or more of the routes available for transport across membranes, such as diffusion, channels or pinocytosis. There have been few studies to establish which route is taken. 

This agrees to internal VolSurf models derived for PAMPA membrane transport [163] to understand passive transcellular transport across membranes. One of our internal models based on 29 compounds characterized by immobilized artificial membrane chromatography by Salminen etal. ]164] shows an of 0.81 and = 0.70 for two PLS components derived using VolSurf descriptors. This is one of the rare examples where ionized starting molecules led to slightly better PLS statistics, while the general chemical interpretation is not affected. 

Molecular size greatly affects transport across cellular membranes. As molecular size increases, transport across membranes decreases, because increases in molecular size will increase "frictional resistance" and decrease the diffusivity through the cell membrane. Since molecular size is generally directly proportional to molecular mass, and molecular mass is easily calculated molecular mass is often used as a descriptor of molecular size. Hence, as a general rule, the lower the molecular mass, the smaller are the molecules composing the substance, and the more easily the substance can cross membranes and be absorbed from the gastrointestinal tract, lung, and skin. 

Inside the inner membrane of a mitochondrion is a viscous region known as the matrix (Fig. 1-9). Enzymes of the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle and the Krebs cycle), as well as others, are located there. For substrates to be catabolized by the TCA cycle, they must cross two membranes to pass from the cytosol to the inside of a mitochondrion. Often the slowest or rate-limiting step in the oxidation of such substrates is their entry into the mitochondrial matrix. Because the inner mitochondrial membrane is highly impermeable to most molecules, transport across the membrane using a carrier or transporter (Chapter 3, Section 3.4A) is generally invoked to explain how various substances get into the matrix. These carriers, situated in the inner membrane, might shuttle important substrates from the lumen between the outer and the inner mitochondrial membranes to the matrix. Because of the inner membrane, important ions and substrates in the mitochondrial matrix do not leak out. Such permeability barriers between various subcellular compartments improve the overall efficiency of a cell. 

Many solute properties are intertwined with those of the ubiquitous solvent, water. For example, the osmotic pressure term in the chemical potential of water is due mainly to the decrease of the water activity caused by solutes (RT In aw = —V ri Eq. 2.7). The movement of water through the soil to a root and then to its xylem can influence the entry of dissolved nutrients, and the subsequent distribution of these nutrients throughout the plant depends on water movement in the xylem (and the phloem in some cases). In contrast to water, however, solute molecules can carry a net positive or negative electrical charge. For such charged particles, the electrical term must be included in their chemical potential. This leads to a consideration of electrical phenomena in general and an interpretation of the electrical potential differences across membranes in particular. Whether an observed ionic flux of some species into or out of a cell can be accounted for by the passive process of diffusion depends on the differences in both the concentration of that species and the electrical potential between the inside and the outside of the cell. Ions can also be actively transported across membranes, in which case metabolic energy is involved. 

Most dmgs bind to a limited number of sites on the albumin molecule. Binding to plasma albumin is generally easily reversible, so that dmg molecules bound to albumin will be released as the level of free dmg in the blood declines. Dmgs bound to albumin (or other proteins) are attached to a unit too large to be transported across membranes. They are thus prevented from reacting with receptors or from entering the sites of dmg metabolism or dmg elimination, until they dissociate from the protein. 

The placenta is both a transport and a metabolizing organ. Transport is accomplished by simple diffusion, facilitated diffusion, active transport across membranes, and by special processes such as pinocytosis, phagocytosis, specific transport molecules, and channels in the barrier . The placenta also contains a full complement of mixed function oxidases located in the microsomal and mitochondrial subcellular fractions capable of induction and metabolism of endogenous and exogenous chemicals. 

Simulated profiles are shown in Figure 12b for the case where the tip is positioned between two closely spaced pores. Here the tip and its insulating sheath partially block the pore, effectively reducing the diffusive flux of the electroactive molecule through the pore. The simulated profiles illustrate the complex nature of probing mass transport across membranes at small tip-to-sample separations. 

Active transport Molecules and ions can be transported across membranes by a variety of mechanisms. Transport mechanisms that require the expenditure of energyusually the hydrolysis of ATPare known as active-transport mechanisms. 

Note that only pores with r > rs participate, because the hindrance factor is zero for r = rs (eq 11). The net number of molecules transported across the membrane is the time integral of Ns over the duration of the simulation and is a quantity that should be measurable for different experimental conditions, particularly different pulse magnitudes, durations, and shapes. The terms... 

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