Membrane transport simple diffusion

Another important vitamin is folate, which is required for purine and pyrimidine nucleotide synthesis. Since folate and its derivatives are generally lipo-phobic anions, they do not traverse biological membranes via simple diffusion but rather have to be taken up into the cells by specific transport processes... 

This mechanism is important for compounds that lack sufficient lipid solubility to move rapidly across the membrane by simple diffusion. A membrane-associated protein is usually involved, specificity, competitive inhibition, and the saturation phenomenon and their kinetics are best described by Michaelis-Menton enzyme kinetic models. Membrane penetration by this mechanism is more rapid than simple diffusion and, in the case of active transport, may proceed beyond the point where concentrations are equal on both... 

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. 

The three ways by which substances, including drugs, can cross cell membranes are simple diffusion, facilitated diffusion and active transport. 

Figure 5.11 Facilitated transport proteins in cell membranes. Unlike simple diffusion through the membrane bilayer, facilitated transport systems become saturated as the solute concentration difference increases. In this hypothetical example, the permeability of the membrane in simple diffusion is 0.4 (units of flux/concentration).

It is clear that the set of molecules that we will deal with, i.e. those for whom no specific transport system exists, will be defined by elimination. If there is no evidence for the existence of a specific mode of transport for the test molecule we will assume that this molecule crosses the cell membrane by simple diffusion, if it crosses the membrane at all. Such an assignment is, of course, temporary. As soon as evidence arises for the intervention of a specific system for the transport of our test molecule, this molecule will then be eliminated from the hst of those entering by simple diffusion. (Some molecules will of course cross the membrane both by simple diffusion and by a specific system, in parallel.)... 

This type of membrane ensures simple diffusion, namely the transport velocity is directly proportional to the concentration difference across the membrane. Thus, when an equilibrium is reached, the internal and external concentrations of the drug are the same. The transport velocity is affected by molecular weight, lipid solubility, and charge, but not greatly by temperature. 

Regarding phytochemicals, polyphenols and llavonoids in particular, their major route of entry is by oral ingestion, since they are consumed as part of a normal diet. Their bioavailability, similarly to what happens with other xenobiotics ingested orally, can be influenced by several factors. The physicochemical characteristics of the compound, such as the size of the molecule, its lipid/water solubility, or its pKa, can dictate its ability to cross a membrane by simple diffusion or not. For example, due to its size, larger molecules may imply other transport processes rather than diffusion. If the compound is hydrophiUc, it is unlikely to cross a membrane freely, but if it is too lipophilic, it may not be completely soluble in gastric secretions which can also make its absorption difficult. In addition, if the compound has ionic charge, it is not probable to cross biological membranes by diffusion and may involve other process to enter the cell. 

This emphasis on dilute solutions is found in the historical development of the basic laws involved, as described in Section 2.1. Sections 2.2 and 2.3 of this chapter focus on two simple cases of diffusion steady-state diffusion across a thin film and unsteady-state diffusion into an infinite slab. This focus is a logical choice because these two cases are so common. For example, diffusion across thin films is basic to membrane transport, and diffusion in slabs is important in the strength of welds and in the decay of teeth. These two cases are the two extremes in nature, and they bracket the behavior observed experimentally. In Section 2.4 and Section 2.5, these ideas are extended to other examples that demonstrate mathematical ideas useful for other situations. 

Under certain conditions, the transfer of various molecules across the membrane is relatively easy. The membrane must contain a suitable transport mediator , and the process is then termed facilitated membrane transport . Transport mediators permit the transported hydrophilic substance to overcome the hydrophobic regions in the membrane. For example, the transport of glucose into the red blood cells has an activation energy of only 16 kJ mol-1—close to simple diffusion. 

LBPs are likely to have conventional roles in the energy metabolism and transport of lipids in nematodes for membrane construction, etc. Many parasitic helminths have deficiencies in the synthesis of some lipids and so their lipid acquisition, transport and storage mechanisms clearly need to be specialized and therefore pertinent to the host-parasite relationship (Barrett, 1981). From a practical point of view, lipid transporter proteins may also be important in the delivery of anthelmintic drugs to their target most anthelmintics are hydrophobic and if they do not distribute to their site of action within the parasites by simple diffusion across and along membranes, then the parasite s own carrier proteins may be involved. 

The cellular mechanism of action of hydrocortisone, a glucocorticoid, is also related to proteins but not by the enhancement of cAMP production. Hydrocortisone is transported by simple diffusion across the membrane of the cell into the cytoplasm and binds to a specific receptor The steroid-receptor complex is activated and enters the nucleus, where it regulates transcription of specific gene sequences into ribonucleic acid (RNA). Eventually, messenger RNA (mRNA) is translated to form specific proteins in the cytoplasm that are involved in the steroid-induced cellular response. 

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... 

Substances can be transported across epithelial membranes by simple passive diffusion, carrier-mediated diffusion, and active transport, in addition to other specialized mechanisms, including endocytosis. 

This refers to the transport across the epithelial cells, which can occur by passive diffusion, carrier-mediated transport, and/or endocytic processes (e.g., transcytosis). Traditionally, the transcellular route of nasal mucosa has been simply viewed as primarily crossing the lipoidal barrier, in which the absorption of a drug is determined by the magnitude of its partition coefficient and molecular size. However, several investigators have reported the lack of linear correlation between penetrant lipophilicity and permeability [9], which implies that cell membranes of nasal epithelium cannot be regarded as a simple lipoidal barrier. Recently, compounds whose transport could not be fully explained by passive simple diffusion have been investigated to test if they could be utilized as specific substrates for various transporters which have been identified in the... 

The fate of a drag in vivo is dictated by a variety of physiochemical properties, including size, lipophilicity, and charge. These properties determine how a drag is absorbed into the blood, distributed throughout the body, metabolized, and eventually eliminated. While movement of a drug molecule can occur through simple diffusion, there are many transporter proteins expressed on cell membranes to assist... 

The resorption process is facilitated by the large inner surface of the intestine, with its brush-border cells. Lipophilic molecules penetrate the plasma membrane of the mucosal cells by simple diffusion, whereas polar molecules require transporters (facilitated diffusion see p. 218). In many cases, carrier-mediated cotransport with Na"" ions can be observed. In this case, the difference in the concentration of the sodium ions (high in the intestinal lumen and low in the mucosal cells) drives the import of nutrients against a concentration gradient (secondary active transport see p. 220). Failure of carrier systems in the gastrointestinal tract can result in diseases. 

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... 

A parameter (usually symbolized by P, and often containing a subscript to indicate the specific ion) that is a measure of the ease with which an ion can cross a unit area of membrane by simple (or passive) diffusion through a membrane experiencing a 1.0 M concentration gradient. For a particular biological membrane, the permeabilities are dependent on the concentration and activity of various channel or transporter proteins. In an electrically active cell (e.g., a neuron), increasing the permeability of K+ or CF will usually result in hyperpolarization of the membrane. Increasing will cause depolarization. 

Any volatile material, irrespective of its route of administration, has the potential for pulmonary excretion. Certainly, gases and other volatile substances that enter the body primarily through the respiratory tract can be expected to be excreted by this route. No specialized transport systems are involved in the loss of substances in expired air simple diffusion across cell membranes is predominant. The rate of loss of gases is not constant it depends on the rate of respiration and pulmonary blood flow. 

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