Passive transport facilitated

Substances move through cell membranes by diffusion (passive transport), facilitated transport, and active transport. 

The transport mechanisms that operate in distribution and elimination processes of drugs, drug-carrier conjugates and pro-drugs include convective transport (for example, by blood flow), passive diffusion, facilitated diffusion and active transport by carrier proteins, and, in the case of macromolecules, endocytosis. The kinetics of the particular transport processes depend on the mechanism involved. For example, convective transport is governed by fluid flow and passive diffusion is governed by the concentration gradient, whereas facilitated diffusion, active transport and endocytosis obey saturable MichaeUs-Menten kinetics. 

Carrier-mediated passage of a molecular entity across a membrane (or other barrier). Facilitated transport follows saturation kinetics ie, the rate of transport at elevated concentrations of the transportable substrate reaches a maximum that reflects the concentration of carriers/transporters. In this respect, the kinetics resemble the Michaelis-Menten behavior of enzyme-catalyzed reactions. Facilitated diffusion systems are often stereo-specific, and they are subject to competitive inhibition. Facilitated transport systems are also distinguished from active transport systems which work against a concentration barrier and require a source of free energy. Simple diffusion often occurs in parallel to facilitated diffusion, and one must correct facilitated transport for the basal rate. This is usually evident when a plot of transport rate versus substrate concentration reaches a limiting nonzero rate at saturating substrate While the term passive transport has been used synonymously with facilitated transport, others have suggested that this term may be confused with or mistaken for simple diffusion. See Membrane Transport Kinetics... 

Passive transport or facilitated diffusion has no energy requirement and is defined as transport of molecules down their concentration gradient (high to low concentration). 

Passive transport requires no overt energy expenditure because the substances moving across the membrane are going from an area of higher concentration to one of lower concentration. The two types of passive transport are simple diffusion (osmosis) and facilitated diffusion. Molecules which may undergo simple diffusion can be found in Table 4. They are... 

Passive diffusion, active transport, facilitated diffusion, phago-/pinocytosis, and filtration. 

Membrane proteins lower the activation energy for transport of polar compounds and ions by providing an alternative path through the bilayer for specific solutes. Proteins that bring about this facilitated diffusion, or passive transport, are not enzymes in the usual sense their substrates are moved from one compartment to another, but are not chemically altered. Membrane proteins that speed the movement of a solute across a membrane by facilitating diffusion are called transporters or permeases. 

Drugs and other substances that pass through biologic membranes usually do so via passive diffusion, active transport, facilitated diffusion, or some special process such as endocytosis (Fig. 2-2). Each of these mechanisms is discussed here. 

Passive Diffusion Active Transport Facilitated Endocytosis... 

Figure 11.1 Schematic examples of passive diffusion, facilitated transport and coupled transport. The facilitated transport example shows permeation of oxygen across a membrane using hemoglobin as the carrier agent. The coupled transport example shows permeation of copper and hydrogen ions across a membrane using a reactive oxime as the carrier agent...

Passive transport The passive transport of molecules across a membrane does not require an input of metabolic energy. The rate of transport (diffusion) is proportional to the concentration gradient of the molecule across the membrane. There are two types of passive transport simple diffusion and facilitated diffusion. 

Transport by facilitated diffusion A large number of molecules and ions were shown to permeate membranes considerably faster than expected from their lipid-water partitioning behavior. This led to the recognition of additional transport mechanisms. Systematic investigations of permeability rates in membranes, reconstituted membranes, and membrane models as functions of the temperature of the nature and concentration of the permeant in the absence and in the presence of additives, suggested three different facilitated passive transport mechanisms ... 

Secondary active transport Secondary active transport is more complex. It involves the permeation of two different substances (A and B) across the membrane. The transport of A is active - it is an uphill process driven by the chemical reaction X—>Y. The transport of B is passive, but facilitated by a carrier C, which co-transports A (Equation 3). Co-transport is defined above in the section on passive transport. 

Several mechanisms for the transport of ions are operative (1) active transport of the ion against a concentration gradient by an ATP-driven membrane carrier, (2) passive carrier facilitated transport, (3) passive diffusion dependent upon the abihfy of the ion or complex to pass the membrane. Sodium,... 

In contrast to active transport, passive transport as a whole does not involve energy consumption and, therefore, only can work down a concentration gradient (or other types of gradients, such as electrochemical potential, thermal, or pressure gradients). In other words, passive transport of molecules equalizes their chemical potential on both sides of the membrane. The process of passive transport can be subdivided into two different mechanisms passive diffusion and facilitated transport. Passive diffusion is a physico-chemical process, whereas in facilitated transport, molecules pass through the membrane via special channels or are translocated via carrier proteins. Both passive diffusion and facilitated transport, in contrast to active transport, follow a gradient, where facilitation merely lowers the activation energy for the transport process. 

Figure 1 Pathways of the intestinal barrier. A paracellular passive diffusion, B transcellular passive diffusion, CF influx/efflux facilitated transport facilitated by membrane proteins, G transcytosis, and H endocytosis (reprinted from Reference 2 with kind permission from Dr. Jon Vabeno and Dr. Roy...

The lipid bilayer of biological membranes, as discussed in Chapter 12. is intrinsically impermeable to ions and polar molecules. Permeability is conferred by two classes of membrane xoXems, pumps and channels. Pumps use a source of free energy such as ATP or light to drive the thermodynamically uphill transport of ions or molecules. Pump action is an example of active transport. Channels, in contrast, enable ions to flow rapidly through membranes in a downhill direction. Channel action illustrates passive transport, or facilitated diffusion. 

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