Sodium cotransport system

The biotin-dependent decarboxylases of anerobic microorganisms are transmembrane proteins. In addition to their roles in the metabolism of ox-aloacetate, methylmalonyl CoA, and glutaconyl CoA, they serve as energy transducers. They tr ansport 2 mol of sodium out of the cell for each mole of substrate decarboxylated. The resultant sodium gradient is then used for active tremsport of substrates by sodium cotransport systems, or maybe used to drive ATP synthesis in a similar manner to the proton gradient in mammalian mitochondria (Buckel, 2001). 

Tyrosine hydroxylase 1 Thiazide diuretics, a group of drugs with moderate diuretic activity, includes hydrochlorothiazide, chlorthalidone, and xipamide. They decrease active reabsorption of sodium and accompanying chloride by binding to the chloride site of the electroneutral Na+/CF cotransport system in the distal convoluted tubule and inhibiting its action. 

The melibiose carrier MelB of E. coli is a well-studied sodium symport system. This carrier is of special interest, because it can also use protons or lithium ions for cotransport. The projection structure of MelB has been solved at 8 A resolution [107]. The 12 TM helices are arranged in an asymmetrical pattern similar to the previously solved structure of NhaA, which, however, follows an antiport mechanism (Na+ ions out of the cell and H+ into the cell). 

By application of the whole-cell mode of the patch clamp technique to freshly isolated cells of convoluted proximal tubules, the sodium-alanine cotransport system could be investigated in detail (Hoyer and Gogelein 1991). 

The brush border of the kidney cortex has a sodium-biotin cotransport system similar to that in the intestinal mucosa, thus providing for reabsorption of free biotin filtered into the urine. It is only when this mechanism is saturated (it has a relatively low K n) that there will be a significant excretion of biotin. 

About 70% of the filtered Na and K is resorbed in the proximal tubule. Sodium is cotransported with glucose and the amino adds, resulting in the resorption of over 99% of these nutrients. Cotransport of Na with bicarbonate results in resorption of 80 to 90% of the filtered bicarbonate. The uptake of these nutrients at the apical membrane occurs by Na mino acid and Na-glucose cotransport systems. One of two sodium ions are cotransported with each glucose. Seven Na-amino acid cotransport systems have been found in the renal tubule. These include systems specific for acidic amino acids, basic amino acids, glycine, neutral amino acids, cysteine, and cystine. One or more sodium ions are cotransported with each amino acid. 

Lithium also enters the chloride-dependent sodium-potassium cotransport system, inhibited by furosemide (129). Lithium and rubidium in the external medium can be simultaneously transported, and it is thought that they can replace sodium and potassium, respectively... 

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. 

Bussolati, O., Laris, P.C., Rotoli, B.M., DalFAsta, V., Gazzola, G.C. (1992). Transport system ASC for neutral amino acids. An electroneutral sodium/amino acid cotransport sensitive to the membrane potential. J. Biol. Chem. 267, 8330-8335. 

Synthesis of acetylcholine Choline is transported from the extracellular fluid into the cytoplasm of the cholinergic neuron by a carrier system that cotransports sodium and can be inhibited by the drug hemicholinium. Choline acetyltransferase (CAT) catalyzes the reaction of choline with acetyl CoA to form acetylcholine in the cytosol. 

Sodium is also required in many nutrient transport systems. The transport of glucose, amino acids, and various ions across membranes may require the cotransport of sodium ions. The transport proteins that mediate the passage of these nutrients across the membrane recognize and bind both sodium and the nutrient. Na and K are both used by Na,K-ATPase. Na,K-ATPase is a membrane-boimd protein whose function is intimately involved with the functioning of the Na-de-pendent nutrient transport systems, as described in Chapter 2. Sodium ions have proven effective in supporting the activity of thrombin, a protein of the blood clotting cascade (Cera et ah, 1995). 

Most of the filtered sodium is resorbed, not by the distal tubule, but by more proximal segments of the renal tubule. Sodium resorption in these regions can be regulated, though the adjustments that occur are not as important to maintaining Na balance as those occurring in the distal tubule. The transport systems to be described involve the resorption of glucose, amino acids, bicarbonate, potassium, and chloride. Sodium ions are resorbed, or cotransported, with all of these nutrients. 

---