Sodium-dependent transporter

Although absolute proof is still lacking it seems clear that NTCP is the major sodium-dependent transporter of bile acids, although a minor role for other proteins cannot be excluded. It has now been isolated from rat, mouse, rabbit and human. The rat polypeptide was first expressed in Xenopus laevis oocytes and shown to be a 362 amino acid glycoprotein with 7 or 9... 

In the human body choline is needed for the synthesis of phospholipids in cell membranes, methyl metabolism, transmembrane signaling and lipid cholesterol transport and metabolism [169]. It is transported into mammalian cells by a high-affinity sodium-dependent transport system. Intracellular choline is metabolized to phosphorylcholine, the reaction being catalyzed by the enzyme choline... 

Biotin is essential for cell proliferation. Peripheral blood mononuclear cells appear to take up biotin by a system that is distinct from the sodium-dependent multivitamin transporter that is responsible for intestinal and renal uptake of biotin (Section 11.1). In response to mitogenic stimuli the uptake of biotin increases several-fold, with no change in the activity of the sodium-dependent transporter. At the same time, there is an increase in the rate of expression of methylcrotonyl CoA, propionyl CoA carboxylases, and holocarboxylase... 

Ascorbate enters cells byway of sodium-dependent transporters. 

Mohrmann M, Pauli A, RItzer M, Schonfeld B, Seifert B and Brandis M. Inhibition of sodium-dependent transport systems in EEC-PK1 cells by metabolites of Ifosfamide. Renal Physiol Blochem 15, 289-301,1992... 

Absorption of vitamin C from the small intestine is a carrier-mediated process that requires sodium at the luminal surface. Transport is most rapid in the ileum and resembles the sodium-dependent transport of sugars and amino acids, but the carrier is distinct for each class of compound. Some ascorbate may also enter by simple diffusion. With dietary intake less than 100 mg/d, efficiency of absorption is 80-90%. With intake equal to the RDA, plasma ascorbate is 0.7-1.2 mg/dL, and the ascorbate pool size is 1500 mg. Scurvy becomes evident when the pool is less than 300 mg, at which point plasma ascorbate is 0.13-0.24 mg/dL. Highest tissue concentrations of ascorbate are in the adrenal gland (cortex > medulla). 

Transporter proteins that regulate the synaptic concentrations of Glu are essential in keeping the basal levels of this EAA neurotransmitter low and in helping to terminate the responses to neuronally released Glu. These high-affinity, sodium-dependent transporters are so efficient at sequestering Glu from the synaptic cleft that the concentration of Glu inside the presynaptic terminal usually is several thousand-fold greater than that found in the synapse (5). 

Membrane chloride transport (e.g. sodium-dependent transport. Renal brush-border, GABAa receptor),... 

The mechanism of DHAA uptake by luminal membranes of human jejunum has pharmacological characteristics that clearly differ from those of ascorbate uptake. Sodium-independent carriers take up DHAA by facilitated diffusion, and these are distinct from the sodium-dependent transporters of ascorbate. Glucose inhibits ascorbate uptake but not DHAA uptake, which raises the possibility that glucose derived from food may increase the bioavailability of DHAA relative to ascorbate (Malo and Wilson, 2000). Human enterocytes contain reductases that convert DHAA to ascorbate (Buffinton and Doe, 1995). This conversion keeps the intracellular level of DHAA low, and the resulting concentration gradient favors uptake of oxidized AA across the enterocyte plasma membrane. 

Transcellular transport mechanisms are responsible for the transport of free amino acids through epithelial cells and are mainly present in cells of the intestinal mucosa and the renal tubules. Most amino acids are transported via a sodium-dependent transport system. However, sodium-independent transport and passive diffusion exist. Transmembrane transporters may be specific for single amino acids (e.g. histidine, glycine) or for groups of amino acids (e.g. dibasic amino acids, dibasic amino acids and cystine, neutral amino acids or dicarboxylic amino acids). 

Active transport is the accumulation of a higher concentration of a compound on one side of a cell membrane than on the other, without chemical modification such as phosphorylation. The process is dependent on hydrolysis of ATP to ADP and phosphate, either directly, as in the case of ion pumps, or indirectly, as is the case when metabolites are transported by sodium-dependent transporters. 

Figure 3.8 The role of ATP in active transport — generation of a proton gradient linked to the sodium pump and sodium-dependent transporters.

Synonymously called the solute carrier 6 family (SLC-6), NSS members include the sodium-and chloride-dependent transporters for GABA, dopamine, serotonin, norepanephrine and glycine, but also just sodium-dependent transporters of amino acids. Thus, the protein family is of particular medical importance, as many CNS diseases like depression, anxiety or epilepsy can be targeted by inhibiting transporters (Iversen, 1971). 

The amormt of absorbed riboflavin that can remain within the body and the circulation (in blood plasma) is strictly regulated by glomerular and tubular filtration and tubular reabsorption in the kidneys. The latter is an active, saturable, sodium-dependent transport process, with characteristics similar to those of active transport in the gastrointestinal tract. It is responsible for the very sharp and characteristic transition between minimal urinary excretion of riboflavin at low intakes, and a much higher level of excretion, proportional to intake, at higher intakes. This transition point has been extensively used to define and to measure riboflavin status and requirements (see below), and to permit studies of intestinal absorption in vivo (see above). Excretion of riboflavin is affected by some chemicals (such as boric acid, which complexes with it), and by certain diseases and hormone imbalances. 

---