Monosaccharide transport system

Several attempts have been made to facilitate the intestinal absorption and tissue distribution of less permeable componnds by ntilizing monosaccharide transport systems, throngh modification of the parent componnds to sngar analogs. The intestinal brnsh border membrane transport of hexose can be attributed to a Na" /glucose cotransporter (SGLTl) for D-glucose,... 

Antiparasitic activities have been demonstrated for cytochalasins B (1088), D (1091), E (1096), and for dihydrocytochalasin B, which inhibit growth and differentiation and influence excystation/encystation of the dimoeha. Entamoeba invadens (720). Cytochalasin B (1088) is able also to influence monosaccharide transport systems (721-725) and hormone release (726, 727). Moreover, in 1992, the antiviral cytochalasan L-696,474 (1139, Scheme 14.3) was discovered, exhibiting an inhibitory effect on HIV-1-protease (728-730). 

F. C. Battaglia and P.J. Randle, Regulation of Glucose Uptake by Muscle. IV. The Specificity of Monosaccharide Transport Systems in Rat Diaphragm Muscle, Biochem. J. 75, 408-416 (1960). 

Carbohydrates mainly occur in food in the form of polymers (starches and glycogen). They are cleaved by pancreatic amylase into oligosaccharides and are then hydrolyzed by glycosidases, which are located on the surface of the intestinal epithelium, to yield monosaccharides. Glucose and galactose are taken up into the enterocytes by secondary active cotransport with Na"" ions (see p. 220). In addition, monosaccharides also have passive transport systems in the intestine. 

Glucose cannot diffuse directly into cells, but enters by one of two transport mechanisms a Na+-independent, facilitated diffusion transport system or a Na+-monosaccharide co-transporter system. 

Glucuronic acid and sialic acid are normally present in conjugated forms. After degradation of these components in lysosomes, the free monosaccharides are released by a specific membrane transport system. The lysosomal sialic acid transporter from rat liver has been purified to apparent homogeneity in a reconstitutively active form. The transporter recognized structurally different types of acidic monosaccharides such as sialic acid, glucuronic acid, and iduronic acid. The transport was proton gradient dependent, and saturable with a of approximately 0.4mM [211]. 

Glucose and galactose compete for a common transport system. This system is an active transport system i.e., the monosaccharides are absorbed against a concentration gradient, it is saturable and obeys Michaelis-Menten... 

The dietary carbohydrates also include sucrose and lactose. Specific disaccharidases which convert these sugars into their constituent monosaccharides are present in the brush border of the intestinal epithelial cells. Only monosaccharides can be absorbed and an active transport system ensures that glucose, galactose and other sugars having the structural features shown below... 

Synthesis. The synthases are present at the endomembrane system of the cell and have been isolated on membrane fractions prepared from the cells (5,6). The nucleoside diphosphate sugars which are used by the synthases are formed in the cytoplasm, and usually the epimerases and the other enzymes (e.g., dehydrogenases and decarboxylases) which interconvert them are also soluble and probably occur in the cytoplasm (14). Nevertheless some epimerases are membrane bound and this may be important for the regulation of the synthases which use the different epimers in a heteropolysaccharide. This is especially significant because the availability of the donor compounds at the site of the transglycosylases (the synthases) is of obvious importance for control of the synthesis. The synthases are located at the lumen side of the membrane and the nucleoside diphosphate sugars must therefore cross the membrane in order to take part in the reaction. Modulation of this transport mechanism is an obvious point for the control not only for the rate of synthesis but for the type of synthesis which occurs in the particular lumen of the membrane system. Obviously the synthase cannot function unless the donor molecule is transported to its active site and the transporters may only be present at certain regions within the endomembrane system. It has been observed that when intact cells are fed radioactive monosaccharides which will form and label polysaccharides, these cannot always be found at all the membrane sites within the cell where the synthase activities are known to occur (15). A possible reason for this difference may be the selection of precursors by the transport mechanism. 

In the mammal, complex polysaccharides which are susceptible to such treatment, are hydrolyzed by successive exposure to the amylase of the saliva, the acid of the stomach, and the disaccharidases (e.g., maltase, invertase, amylase, etc.) by exposure to juices of the small intestine. The last mechanism is very important. Absorption of the resulting monosaccharides occurs primarily in the upper part of the small intestine, from which the sugars are earned to the liver by the portal system. The absorption across die intestinal mucosa occurs by a combination of active transport and diffusion. For glucose, the aclive transport mechanism appears to involve phosphorylation The details are not yet fully understood. Agents which inhibit respiration (e.g., azide, fluoracetic acid, etc.) and phosphorylation (e.g., phlorizin), and those which uncouple oxidation from phosphorylation (e.g., dinitrophenol) interfere with the absorption of glucose. See also Phosphorylation (Oxidative). Once the various monosaccharides pass dirough the mucosa, interconversion of the other... 

The demonstration by Crane (1960, 1965) that Na+ ions were essential for the translocation of monosaccharides by segments of the intestine brought in a new era of understanding of the central role of ion coupled transport, particularly in higher organisms. While Na+ is clearly the predominant cation involved in cation driven solute accumulation in mammalian systems, current work has provided examples of H+ driven solute transport in intestine and kidney (Jessen et al., 1989 Ganapathy and Leibach, 1986). Conversely, in yeast and bacteria, H+ driven mechanisms are in the majority (Seaston et al., 1973 Hirata et al., 1973), but examples of Na+-cou-pled fluxes exist, e.g., proline transport (Dibrov, 1991). 

D) monosaccharides are transported to adipose tissue via the lymphatic system. 

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