Cell membranes transmembrane transport

If the intensity and duration of the applied electric pulse are controlled properly, the created nanopores will be reversible and the cell will remain alive during and after the electroporation. The created nanopores on the cell membrane may be treated as a pathway to insert different biological nanoparticles such as qdots and DNA into the cells. Because of the difference of the electric potential on two sides of the cell membrane (transmembrane potential), the electrokinetics plays a decisive role on transporting... 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

Mammalian intestinal absorption requires the presence of two receptors and two transporters, which is itself a unique feature. Specific transporters such as intrinsic factor, transcobalamin, and haptocorrin have been characterized,1113 as well as a number of receptors for passage across cell membranes. A number of biochemical studies on cell uptake1114 and receptors1115,1116 of cobala-mins have been reported. Genetic disorders that impair the synthesis, transport, or transmembrane passage of cobalamins and their consequences have been reviewed.1117,1118... 

C-termini and a large glycosylated extracellular loop between transmembrane domains 3 and 4. The proteins show the most homology in their transmembrane spanning domains, particularly domains 1, 2, and 4-8, which may be involved in moving the transmitter across the membrane. The transporters are substrates for PKC-dependent phosphorylation, which reduces their activity. The dopamine transporter is phosphorylated on the extreme end of the N-terminal tail, and consensus phosphorylation sites for various other kinases are present in the intracellular loops and domains [20-22] (Fig. 12-4). The dopamine and norepinephrine transporters form functional homo-oligomers, although it is not known if this is required for transport activity, and the transporters also interact with many other membrane proteins that may control their cell-surface expression or other properties. 

The ideas of Overton are reflected in the classical solubility-diffusion model for transmembrane transport. In this model [125,126], the cell membrane and other membranes within the cell are considered as homogeneous phases with sharp boundaries. Transport phenomena are described by Fick s first law of diffusion, or, in the case of ion transport and a finite membrane potential, by the Nernst-Planck equation (see Chapter 3 of this volume). The driving force of the flux is the gradient of the (electro)chemical potential across the membrane. In the absence of electric fields, the chemical potential gradient is reduced to a concentration gradient. Since the membrane is assumed to be homogeneous, the... 

Many experimental variations are possible when performing uptake studies [246]. In a simple experiment for which the cells are initially free of internalised compound, the initial rates of transmembrane transport may be determined as a function of the bulk solution concentrations. In such an experiment, hydrophilic compounds, such as sugars, amino acids, nucleotides, organic bases and trace metals including Cd, Cu, Fe, Mn, and Zn [260-262] have been observed to follow a saturable uptake kinetics that is consistent with a transport process mediated by the formation and translocation of a membrane imbedded complex (cf. Pb uptake, Figure 6 Mn uptake, Figure 7a). Saturable kinetics is in contrast to what would be expected for a simple diffusion-mediated process (Section 6.1.1). Note, however, that although such observations are consistent... 

CF is caused by the absence of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein is required for the transport of chloride ions across cell membranes. On the molecular level, there is a mutation in the gene that encodes for CFTR. As a result, CFTR cannot be processed properly by the cell and is unable to reach the exocrine glands to assume its transport function. 

Cardiac glycosides (CG) bind to the extracellular side of Na+/lC-ATPases of cardiomyocytes and inhibit enzyme activity. The Na+/lC-ATPases operate to pump out Na+ leaked into the cell and to retrieve 1C leaked from the cell. In this manner, they maintain the transmembrane gradients for 1C and Na+, the negative resting membrane potential, and the normal electrical excitability of the cell membrane. When part of the enzyme is occupied and inhibited by CG, the unoccupied remainder can increase its level of activity and maintain Na and 1C transport The effective stimulus is a small elevation of intracellular Na concentration (normally approx. 7 mM). 

In the human body choline is needed for the synthesis of phospholipids in cell membranes, methyl metabolism, transmembrane signaling and lipid cholesterol transport and metabolism [169]. It is transported into mammalian cells by a high-affinity sodium-dependent transport system. Intracellular choline is metabolized to phosphorylcholine, the reaction being catalyzed by the enzyme choline... 

TARGETING CELL MEMBRANE PROTEINS TRANSMEMBRANE TRANSPORTER PROTEINS... 

Some microorganisms produce compounds that can become incorporated into lipid membranes and will facilitate the transmembrane transport of ions, notably K+. These natural products are antibacterial, killing bacteria by lethally altering the transmembrane ion flux. Such antibacterial molecules are called ionophores, or ion carriers, in contrast to other antibacterials, such as polyene antibiotics, which simply produce leakage through the cell membrane. 

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