Regulatory mechanisms of inorganic phosphate homeostasis

Inorganic phosphate (phosphate) is an essential nutrient in the processes of glycolysis, glyconeogenesis, energy metabolism and skeletal mineralization. It serves as the source of phosphate for organic cell constituents such as DNA, RNA, a variety of phosphorylated metabolic intermediates, and the phospholipid constituents of cellular membranes. In addition, phosphorylation of cellular proteins is a major mechanism by which cell function is controlled. The metabolism of phosphate in the body represents a complex interplay between various factors that can affect the digestion, absorption, distribution and excretion of this element. About 80% of phosphate is absorbed from a typical mixed diet. Phosphate absorption in humans has been shown to be linearly related to phosphate intake over the range of 10 to 30 mg/kg body weight per day. Regulation of total body phosphate over long periods requires the coordinated efforts of the kidney and intestine. Under conditions of low dietary phosphate intake, the intestine increases its absorptive effciency to maximize phosphate absorption and the kidney increases renal phosphate transport to minimize urinary phosphate losses. Physiologic conditions associated with life cycle changes, such as growth, pregnancy and lactation, are associated with increased phosphate need and a corresponding increase in phosphate absorption. It is well known that the rate of phosphate excretion and adaptation to dietary phosphate is changed with aging. Absorbed phosphate is either eliminated by the kidney, incorporated into organic forms in proliferating cells, or deposited as a component of bone mineral (hydroxyapatite). The crucial regulated step in phosphate homeostasis is the transport of phosphate across the renal proximal tubule. Type IIa sodium-dependent phosphate (Na/Pi) cotransporter (NPT2a) is the major molecule in the renal proximal tubule and is regulated by hormones and nonhormonal factors.