Cell membranes carrier proteins

The movement of solutes from the external environment into the cell is usually achieved using cell membrane-spanning proteins that facilitate solute transfer. These are necessary, since most solutes (e.g. sugars, amino acids, salts) will not readily diffuse through the hydrophobic cell membrane. Movement of solutes into the epithelial cell can involve a variety of protein carriers or channels including (see Figure 1) ... 

In the body, drug molecules cross cell membranes, are transported across cells, and many are altered by being metabolised. These movements and changes involve interaction with membranes, carrier proteins and enzymes, either as individual cheiiucal reactions or as processes. The rate at which these movements or changes can take place is subject to important influences that are referred to as the order of reaction or process. In biology generally, two orders of such reactions are recognised, and are summarised as follows ... 

As already explained in Section 7.4, the major ions of Class A (e.g., Na, K, Ca) do not have a high affinity for ligands containing sulfur and nitrogen, and therefore do not bind to the membrane carrier proteins, for transport into the cell. Thus, active ion pumps (Figure 7.2) are required for the movement of these ionic metals against concentration gradients across the hydrophobic membrane (Phillips and Rainbow 1993). 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

Several types of cells are equipped with carrier proteins to transport essential nutrients such as glucose and amino acids that cannot cross the plasma membrane freely because of their hydrophilicity. Intestinal and renal epithelia have long been known to possess specialized Na+ cotransport processes for glucose [205], amino acids [206], and di- and tripeptides [207],... 

In the process of mediated transport, carrier proteins embedded within the plasma membrane assist in the transport of larger polar molecules into or out of the cell. When a given substance attaches to a specific binding site on the carrier protein, the protein undergoes a conformational change such that this site with the bound substance moves from one side of the plasma membrane to the other. The substance is then released. Mediated transport displays three important characteristics influencing its function ... 

Extracellular ligands (hormones, neurotrophins, carrier protein, adhesion molecules, small molecules, etc.) will bind to specific transmembrane receptors. This binding of specific ligand induces the concentration of the receptor in coated pits and internalization via clathrin-coated vesicles. One of the best studied and characterized examples of RME is the internalization of cholesterol by mammalian cells [69]. In the nervous system, there are a plethora of different membrane receptors that bind extracellular molecules, including neurotrophins, hormones and other cell modulators, being the best studied examples. This type of clathrin-mediated endocytosis is an amazingly efficient process, capable of concentrating... 

Figure 1. Solute transfer across an idealised eukaryote epithelium. The solute must move from the bulk solution (e.g. the external environment, or a body fluid) into an unstirred layer comprising water/mucus secretions, prior to binding to membrane-spanning carrier proteins (and the glycocalyx) which enable solute import. Solutes may then move across the cell by diffusion, or via specific cytosolic carriers, prior to export from the cell. Thus the overall process involves 1. Adsorption 2. Import 3. Solute transfer 4. Export. Some electrolytes may move between the cells (paracellular) by diffusion. The driving force for transport is often an energy-requiring pump (primary transport) located on the basolateral or serosal membrane (blood side), such as an ATPase. Outward electrochemical gradients for other solutes (X+) may drive import of the required solute (M+, metal ion) at the mucosal membrane by an antiporter (AP). Alternatively, the movement of X+ down its electrochemical gradient could enable M+ transport in the same direction across the membrane on a symporter (SP). A, diffusive anion such as chloride. Kl-6 refers to the equilibrium constants for each step in the metal transfer process, Kn indicates that there may be more than one intracellular compartment involved in storage. See the text for details...

These methods of solute transfer usually rely on a relatively low intracellular concentration of the solute of interest, so that it will readily diffuse into the cell down the electrochemical gradient (as in the case of ion channels). Alternatively, the solute may be moved into the cell using chemical energy derived from another solute moved in the same direction (co-transport) or opposite direction (countertransport) on the carrier protein (symporters and antiporters respectively). The transfer of the second solute is in turn dependent on an inward electrochemical gradient. Ultimately, these gradients are established by primary, energy-requiring solute pumps (e.g. ATPases), which, on most epithelia, are located on the basolateral/serosal membrane (see Section 5.2 for discussion of ATPases). 

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