The basics of phosphate metabolism

Abstract

Phosphorus is an essential mineral that is, in the form of inorganic phosphate (Pi), required for building cell membranes, DNA and RNA molecules, energy metabolism, signal transduction and pH buffering. In bone, Pi is essential for bone stability in the form of apatite. Intestinal absorption of dietary Pi depends on its bioavailability and has two distinct modes of active transcellular and passive paracellular absorption. Active transport is transporter mediated and partly regulated, while passive absorption depends mostly on bioavailability. Renal excretion controls systemic Pi levels, depends on transporters in the proximal tubule and is highly regulated. Deposition and release of Pi into and from soft tissues and bone has to be tightly controlled. The endocrine network coordinating intestinal absorption, renal excretion and bone turnover integrates dietary intake and metabolic requirements with renal excretion and is critical for bone stability and cardiovascular health during states of hypophosphataemia or hyperphosphataemia as evident from inborn or acquired diseases. This review provides an integrated overview of the biology of phosphate and Pi in mammals.

Keywords: bone; cell metabolism; endocrine regulation; intestine; kidney.

Figure 1:

Daily phosphate fluxes. Average dietary intake of phosphorus is ≈1.4 g, of which ≈0.9 g are net absorbed by the intestine. Absorbed Pi enters the plasma pool, which is in constant exchange with soft tissue and bone. Blood also undergoes constant filtration and kidneys reabsorb 80–90% of filtered Pi. Net renal excretion plus faecal excretion matches daily intake of Pi in subjects in Pi balance. Numbers are average numbers for a 70-kg adult person on a mixed standard diet.

Figure 2:

Functions of phosphate. Pi is a building block for phospholipids in biological membranes, for nucleotides in DNA and RNAs, to form ATP, is involved in intracellular signaling events and is critical for the stability of bone under the form of hydroxyapatite.

Figure 3:

Intestinal absorption of Pi. Phosphate is delivered by diet either as inorganic salt or as organic phosphates that can be cleaved by intestinal alkaline phosphatases or by bacteria-derived phytases. Active absorption is mediated by Na⁺-dependent Pi transporters NaPi-IIb, PiT1 and PiT2 while passive absorption proceeds via the paracellular route.

Figure 4:

Renal reabsorption of Pi. Reabsorption of Pi in the proximal tubule is mediated by three Na⁺-dependent Pi transporters located in the luminal membrane: NaPi-IIa, NaPi-IIc and PiT2. Efflux of Pi at the basolateral membrane occurs through unknown mechanisms. Na⁺/K⁺-ATPases energize transport of Pi across the luminal membrane.

Figure 5:

Endocrine regulation of phosphate homeostasis. The three major endocrine factors regulating phosphate homeostasis and its link to calcium metabolism. For details, see the text.