Facilitated diffusion, sugars

Facilitated diffusion and active transport share many features. Both appear to involve carrier proteins, and both show specificity for ions, sugars, and amino acids. 

The phosphorylation of cytoplasmic sugar and the facilitated diffusion from the cytoplasm to the periplasm are catalyzed by the E-IIs under conditions where they are also active in the vectorial phosphorylation reaction. Therefore, the former two activities should be integral parts of any kinetic scheme representing the mechanism of E-IIs. Such a scheme should explain how vectorial phosphorylation, transport coupled to phosphorylation, is still achieved while the uncoupled pathways are integral parts of the scheme. 

In addition to the passive diffusional processes over lipid membranes or between cells, substances can be transferred through the lipid phase of biological membranes through specialized systems, i.e., active transport and facilitated diffusion. Until recently, the active transport component has been discussed only for nutrients or endogenous substances (e.g., amino acids, sugars, bile acids, small peptides), and seemed not to play any major role in the absorption of pharmaceuticals. However, sufficient evidence has now been gathered to recognize the involvement of transporters in the disposition of pharmaceuticals in the body [50, 127]. 

Special carrier molecules exist for certain substances that are important for cell function and too large or too insoluble in lipid to diffuse passively through membranes, eg, peptides, amino acids, glucose. These carriers bring about movement by active transport or facilitated diffusion and, unlike passive diffusion, are saturable and inhibitable. Because many drugs are or resemble such naturally occurring peptides, amino acids, or sugars, they can use these carriers to cross membranes. 

Facilitated diffusion involves carrier-mediated transport down a concentration gradient. The existence of the carrier molecules means that diffusion down the concentration gradient is much greater than would be expected on the basis of the physicochemical properties of the drag. A much larger number of substances are believed to be transported by facilitated diffusion than active transport, including vitamins such as thiamine, nicotinic acid, riboflavin and vitamin B6, various sugars and amino acids. 

Initially, hexoses are transported inside the cell by facilitated diffusion (Lagunas 1993). As the inner sugar concentration is lower than the external sugar concentration, no energy is necessary for this process. 

Facilitated diffusion is a simple mechanism proposed to explain transport of water soluble compounds. The main characteristics of this transport system are that membrane permeability exceeds that predicted from partition coefficients, transport occurs down a concentration gradient, transport is saturable, and competition occurs between isomers. Facilitated diffusion has been used to explain cellular uptake of sugars and amino acids. 

Carrier-mediated movement of sugars across the plasmalemma of yeasts involves the combination of the sugar with a protein on one side of the plasmalemma, followed by release of the sugar into the cytoplasm on the other side. Such movement is described either as (t) facilitated diffusion, when the movement requires no metabolic energy, or (ii) active transport, which involves the expenditure of metabolic energy. Sugars entering yeast cells by active transport may be accumulated within the cells to a concentration many hundred times the external level. This subject has been reviewed by... 

Fructose is found in the diet as a component of sucrose in fruit, as a free sugar in honey, and in high-fructose com symp (see Fig. 29.1). Fmctose enters epithelial cells and other types of cells by facilitated diffusion on the GLUT V transporter. It is metabolized to intermediates of glycolysis. Problems with fructose absorption and metabolism are relatively more common than with other sugars. 

Xylose is taken up in S. cerevisiae by the glucose transporters [108]. These are permeases that transport sugars by facilitated diffusion [109] (Fig. 3), and have about two orders of magnitude lower affinities towards xylose than glucose (Table 2), which leads to competition between glucose and xylose when simultaneously present in the fermentation medium. When these two sugars were cofermented by recombinant S. cerevisiae the uptake of xylose (15 g 1" ) was severely retarded until the glucose concentration fell below 10 g 1" [110]. 

Figure 7. Sugar permeability plot for bilayer lipid membrane (egg lecithin-cholesterol in n-decane) at 25 °C. The slope of the plot before and after addition of extract is equal to the permeability coefficient. Passive diffusion of D-[ C]glucose (O) and facilitated diffusion ( ) on addition of band 4.5 (sugar transporter) at a concentration of 0.99 (Jig cm to the trans side of the bilayer. (Reproduced with permission from Ref. 44. Copyright 1982 Elsevier Science.)...

With the exception of the phosphotransferase system that is responsible for uptake of several sugars by bacteria, the active uptake of organic solutes is secondary active and coupled via cotransport to the downhill transport of a cation, Na in animal cells and H ions in microorganisms. In transcellular transport in epithelia, such as small intestine and proximal tubule of the kidney, the solutes are accumulated inside the cell via a cotransport mechanism at the luminal membrane, and leave the cell passively presumably by facilitated diffusion at the eontraluminal side. 

Simple diffusion probably accounts for the uptake of undissociated organic acids by the yeast cell. Facilitated diffusion may be involved in the transport of sugars [17], although the fact that some are taken up against a concentration gradient could indicate that active transport occurs [18]. Active transport processes are used to transport amino acids and the ions of potassium, magnesium, phosphorus and sulphate. 

The endothelial cells possess mitoehondria which probably provide the necessary energy for facilitated diffusion of sugars and other transported metabolites, e. g. amino acids. In the absence of a specific transport mechanism, ions and low M, polar nonelectrolytes are also unable to cross the endothelial cells of eerebral capillaries. 

Amino acids, glucose and certain other sugars are taken up by carrier-mediated mechanisms which may be either passive or active according to the type of cell. Active transport processes are particularly highly developed in the cells of the intestinal mucosa and kidney tubules which are specialized for the absorption of material and its transport across the cell. Most other types of cell, e.g. liver, muscle and erythrocytes, take up glucose and amino acids by facilitated diffusion rather than by active transport. 

Table 6. Facilitated Diffusion Systems for Amino Acids and Sugars...

A system in which transport (active or by facilitated diffusion) takes place only when a complex between substrate (amino acid, sugar, or anion), sodium ion, and carrier is formed. Within the cell, dissociation of substrate and sodium ion from the carrier occurs freely. 

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) ... 

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