Sodium phosphate cotransporter

Fig. 11.4. H uman duodenal expression variability of phosphate and ABC transporters (unpublished data). Shaded box indicates 25-75% of expression range, the line within the box marks the median, and error bars indicate 10-90% of expression range. SLC17A4, sodium phosphate cotransporter SLC25A3,...

X-linked hypophosphatemic rickets is caused by abnormal reabsorption of phosphate in the proximal renal tubule, resulting in excessive excretion of phosphate and hence hypophosphatemia. There may also be blunting of the normal increase in calcidiol 1 -hydroxylase activity in response to hypophosphatemia. The gene responsible for the condition has been identified (the PHEX gene) its product is a membrane-bound endopeptidase that normally acts to clear the hormone phosphatonin from the circulation. Phosphatonin acts to decrease the activity of the sodium/phosphate cotransporter in the kidney (Drezner, 2000). 

Foscarnet competitively inhibits Na -Pj cotransport in animal and human kidney proximal tubule brush border membrane vesicles, reversibly inhibiting sodium-dependent phosphate transport [48, 49]. Renal cortical Na-K-ATPase and alkaline phosphatase activity are not inhibited by foscarnet, nor is proline, glucose, succinate, or Na" transport [48,49]. Foscarnet induces isolated phosphaturia without hypophosphatemia in thyroparathyroidectomized rats maintained on a low phosphorus diet, without affecting glomerular filtration rate, urinary adenosine 3 5 -cyclic monophosphate (cAMP) activity, or urinary calcium, sodium or potassium excretion [48,50]. Sodium-Pj cotransport in brush border membrane vesicles from human renal cortex was reported to be even more sensitive to inhibition by foscarnet than in rat renal brush border membrane vesicles [49]. 

About 85% of the body s phosphate occurs in bones, with 14% in soft tissues and about 1.0% in the extracellular fluids. The normal range of phosphate intake is 20 to 50 mmol/day (0-6-1.5 g phosphorus/day). Phosphate is absorbed throughout the small intestines. In the duodenum, it is absorb by an Na-dependent transport mechanism. Here, transport of the phosphate is coupled with die cotransport of a sodium ion. The rate of Na-dependent transport of phosphate is enhanced by 1,25-(0H)2D3, Phosphate transport in the jejunum and ileum occurs by a passive mechanism. The rate of phosphate transport in this case is dependent mainly on the concentration of phosphate in the lumen and is independent of the levels of other nutrients and independent of energy-using processes. About 200 mg of phosphorus is excreted per day in fluids of the gastnointeslinai tract. About two-thirds of this phosphorus is reabsorbed by the gut. 

Pi ions are thought to be absorbed primarily by transcellular mechanisms that involve cotransport with cations, especially sodium (Na ). These rapid mechanisms account for the uptake of Pi ions in blood within Ih after ingestion of a meal. The blood concentration of Pi is less tightly regulated than the serum calcium concentration. Wider fluctuations in serum Pi concentrations reflect both dietary intakes and cellular releases of inorganic phosphates. 

---