Na+-glucose symporter

Predict the effects of the following on the initial rate of glucose transport into vesicles derived from animal cells that accumulate this sugar by means of Na+ symport. Assume that initially A P = 0, ApH = 0 (pH = 7), and the outside medium contains 0.2MNa+, whereas the vesicle interior contains an equivalent amount of K+. 

In E. coli, lactose is taken up by means of proton symport, maltose by means of a binding (ABC-type) protein-dependent system, melibiose by means of Na+ symport, and glucose by means of the phosphotransferase system (PTS). Although this bacterium normally does not transport sucrose, suppose that you isolated a strain that does. How do you determine whether one of the four mechanisms just listed is responsible for sucrose transport in this mutant strain ... 

Amino acids, dipeptides, and some tripeptides are transported from the lumen of the intestine through the membrane of the brush border of the mucosal cells and into the cytoplasm, where the peptides are hydrolyzed to amino acids. Transport of peptides and amino acids is active and analogous to glucose transport i.e., they are transported, together with Na+, across the gut-cell membrane by specific transport proteins called Na+ symports. Between the gut lumen and the cytoplasm of the cell there is a concentration gradient of Na+ that is maintained by Na+/K+ ATPase at the base of the cell adjacent to the blood capillaries this Na+/K ATPase pumps Na+ from the cell into the blood. 

Transport systems can be described in a functional sense according to the number of molecules moved and the direction of movement (Figure 41-10) or according to whether movement is toward or away from equilibrium. A uniport system moves one type of molecule bidirectionally. In cotransport systems, the transfer of one solute depends upon the stoichiometric simultaneous or sequential transfer of another solute. A symport moves these solutes in the same direction. Examples are the proton-sugar transporter in bacteria and the Na+ -sugar transporters (for glucose and certain other sugars) and Na -amino acid transporters in mammalian cells. Antiport systems move two molecules in opposite directions (eg, Na in and Ca out). 

Figure 41-14. The transcellular movement of glucose in an intestinal cell. Glucose follows Na+ across the luminal epithelial membrane. The Na+ gradient that drives this symport is established by Na+ -K+ exchange, which occurs at the basal membrane facing the extra-ceiiuiarfiuid compartment. Glucose at high concentration within the ceii moves "downhill" into the extracel-iuiarfiuid by fadiitated diffusion (a uniport mechanism).

Brain capillary endothelial cells and some neurons also express a Na+-dependent D-glucose symporter, SGLT1 91... 

Brain capillary endothelial cells and some neurons also express a Na+-dependent D-glucose symporter, SGLT1. SGLT1 (SLC5A1) was the first characterized of the large SLC5 family of Na-dependent symporters (SSSF) which transport various solutes and ions into cells [77, 78]. SGLT1 is found mainly in the intestine, trachea,... 

Figure 9.7 (a) The epithelial brush border cells of the small intestine concentrate glucose from the intestinal lumen in symport with Na+ this is driven by the (Na+-K+)-ATPase located on the capillary side of the cell. The glucose is then exported by a passive uniport system. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.) (b) Two Na+-binding sites in the LeuT Na+-dependent pump. (From Gouax and MacKinnon, 2005. Copyright (2005) American Association for the Advancement of Science.)... 

Na+ co-transporter (symport) allows uptake of X (e.g. amino acid or glucose)... 

Co-transport, also known as symport, is the transport of one compound that is obligatorily linked to that of another. An example is the transport of glucose and Na ions (see below). In counter-transport, also known as antiport, the transporter transports one compound in one direction and... 

Some cells couple the pure transport forms discussed on p. 218—i.e., passive transport (1) and active transport (2)—and use this mechanism to take up metabolites. In secondary active transport (3), which is used for example by epithelial cells in the small intestine and kidney to take up glucose and amino acids, there is a symport (S) located on the luminal side of the membrane, which takes up the metabolite M together with an Na" ion. An ATP-dependent Na transporter (Na /lC ATPase see p. 350) on the other side keeps the intracellular Na+ concentration low and thus indirectly drives the uptake of M. Finally, a uniport (U) releases M into the blood. 

Na+-glucose symporter in epithelial cells 2.A.73. HCOsT transporters HCOi -CF antiporter... 

In intestinal epithelial cells, glucose and certain amino acids are accumulated by symport with Na+, down the Na+ gradient established by the Na+K+ ATPase of the plasma membrane (Fig. 11-44). The apical surface of the intestinal epithelial cell is covered with microvilli, long thin projections of the plasma membrane... 

That is, the cotransporter can pump glucose inward until its concentration within the epithelial cell is about 9,000 times that in the intestine. As glucose is pumped from the intestine into the epithelial cell at the apical surface, it is simultaneously moved from the cell into the blood by passive transport through a glucose transporter (GLUT2) in the basal surface (Fig. 11-44). The crucial role of Na+ in symport and antiport systems such as these requires the continued outward pumping of Na+ to maintain the transmembrane Na+ gradient. 

Energetics of Symport Suppose that you determined experimentally that a cellular transport system for glucose, driven by symport of Na+, could accumulate glucose to concentrations 25 times greater than in the external medium, while the external [Na+] was only 10 times greater than the intracellular [Na+]. Would this violate the laws of thermodynamics If not, how could you explain this observation ... 

Active transport of a molecule across a membrane against its concentration gradient requires an input of metabolic energy. In the case of ATP-driven active transport, the energy required for the transport of the molecule (Na+, K+, Ca2+ or H+) across the membrane is derived from the coupled hydrolysis of ATP (e.g Na+/K+-ATPase). In ion-driven active transport, the movement of the molecule to be transported across the membrane is coupled to the movement of an ion (either Na+ or H+) down its concentration gradient. If both the molecule to be transported and the ion move in the same direction across the membrane, the process is called symport (e.g. Na+/glucose transporter) if the molecule and the ion move in opposite directions it is called antiport (e.g. erythrocyte band 3 anion transporter). 

Fig. 4. Ion-driven cotransport mechanisms, (a) Symport process involving a symporter (e.g. Na+/glucose transporter) (b) antiport process involving an antiporter (e.g. erythrocyte band 3 anion transporter).

These indirect approaches suggest that a 75 kDa polypeptide is involved in Na+/glucose symport and a carrier of this size is consistent with cloning data (see below). Procedures involving transporter purification, using reconstitution to follow Na+/glucose symport activity, have not been very successful (Koepsell et al., 1983 Malathi and Takahashi, 1990). Moreover, the sequence identity (or similarity) of the partly purified 75 kDa peptide to the cloned glucose transporter has yet to be established (as of 1995). 

Answer No the symport may be able to transport more than one equivalent of glucose per Na+. 

MDR (blocks efflux of Doxorubicin) T MDR-TR expression (Na+/glucose symport TR PKC) [AI] MDR-TR (mouse H,rNBD2 domain) [34] (cAMP PDE, COX, 5-LOX) [AI, APA, antifungal, inhibits basophil histamine release, pro-apoptotic]... 

The provision of salt and glucose allows for the symport transport of glucose and Na+ (see Figure 4.9) and therefore restoration of a higher osmotic potential in extracellular fluid that draws water in from the gut lumen. 

SGLT-1 and SGLT-2 are Na+-glucose symporters they concentrate glucose (and related hexoses) inside the cell using the energy provided by co-transport of Na+ ions down their electrochemical gradient. 

Sodium Na+-H+ antiport and Na -glucose symport Re-absorbed, 65% Re-absorbed, 25%, ascending loop, Na+-K+ symport Re-absorbed, 5%, Na+-Cr symport Re-absorbed, 5%... 

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