Phosphorus Metabolism

Phosphorus plays a pivotal role in various biological processes. Therefore, a deeper understanding of Phosphorus Homeostasis is essential for management and treatment of conditions causing an imbalance in phosphate metabolism. The widely understood parathyroid hormone (PTH) and vitamin D axis that governs this phosphate homeostasis has been critiqued for its inability to explain a few rare genetic and acquired conditions associated with phosphate imbalance. Such conditions are characterized by normal PTH and activated vitamin D hormone. For example, Tumor Induced osteomalacia, Autosomal Dominant hypophosphatemic rickets, and X-linked hypophosphatemic rickets. Recent studies of such conditions have led to the discovery of additional factors that play an important role in phosphorus homeostasis. These phosphaturetic factors, called “Phosphatonins” include Fibroblast Growth Factor 23 (FGF-23), Fibroblast Growth Factor 7 (FGF7), Frizzled related protein 4 (FRP4), and matrix extracellular phosphoglycoprotein (MEPE).Out of these phosphatonins, FGF-23 has been extensively studied. This article aims to summarize the importance of phosphatonins in hypoand hyperphosphatemic conditions along with the physiological and clinical importance of such factors. Furthermore, we tried to summarize current knowledge regarding diagnosis and management of such conditions. *Corresponding author: Rupesh Raina, Fellow at Rainbow Babies and Children Hospital, Case Western Reserve, Cleveland, OH, USA, E-mail: Rupesh.Raina@ uhhospitals.org Received April 12, 2012; Accepted July 20, 2012; Published July 25, 2012 Citation: Raina R, Garg G, Sethi SK, Schreiber MJ, Simon JF, et al. (2012) Phosphorus Metabolism. J Nephrol Therapeutic S3:008. doi:10.4172/2161-0959. S3-008 Copyright: © 2012 Raina R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Phosphorus is the second most abundant essential mineral in the human body after calcium. It not only plays a role in numerous biologic processes, including energy metabolism and bone mineralization, but also provides the structural framework for DNA and RNA. It is synthesized through various biochemical pathways such as glycolysis and beta oxidation. As a part of signal transduction, phosphate is used in cyclic AMP and products of deoxyribonucleoside diphosphates like dADP, dCDP, dGDP, and dUDP [1]. Approximately 80% to 90% of phosphorus is present in the bones and teeth in the form of hydroxyapatite (Ca10(PO4)6(OH)2) [2]. The remainder is present in extracellular fluid (ECF), soft tissues and erythrocytes. Serum and plasma contain only a small fraction of total body phosphorus in the form of inorganic phosphate, lipid phosphorus, and phosphoric ester phosphorus. Thus, changes in serum phosphate levels do not necessarily reflect the body’s total store of phosphorus. Phosphate Homeostasis A normal diet provides approximately 20 mg/kg/day of phosphorus of which 16 mg/kg/day is absorbed in the small intestine (predominantly in the jejunum) by both para-cellular and intracellular processes. The intra-cellular process is mediated via SodiumPhosphate co-transport present on villi of small intestine. The paracellular pathway is a concentration gradient-dependent, passive transport system. Increase in dietary phosphorus leads to an increase in phosphate absorption with little evidence of an upper limit or saturation of absorption process [2]. Three mg/kg/day of phosphorus is secreted into the intestine via pancreatic and intestinal secretions, giving a net phosphorus absorption of around 13 mg/kg/day. Once absorbed, phosphate/phosphorus enters the ECF and circulation where it is taken up by bones, teeth, and other soft tissues via the action of sodium phosphate co-transporters [1]. Three sodium-phosphate cotransporters have been described: NaPi-I, NaPi-II (a, b, and c) and NaPi-III. NaPi-IIb is localized in the small intestine whereas NaPi-IIa and NaPi-IIc are found in the kidneys, with the former responsible for at least 85% of renal phosphate absorption through intracellular processes (Tables 1 and 2). The rate of reabsorption and mineralization is important in determining the serum phosphorus concentration. Approximately 3 mg/kg/day of phosphorus is exchanged between mineralized bones and the ECF. Phosphate is filtered freely across the glomerulus-about 13 mg/ kg/day in a normal adult-and 60% to 70% of filtered phosphate is reabsorbed in the proximal tubule (with 10% to 15% reabsorbed in the distal tubule). This transport is mediated via a sodium-gradient dependent process and sodium-phosphate co-transporters (type I and type IIa/IIc) on the luminal brush border membrane of the proximal tubules [3]. Seven mg/kg/day of phosphorus is excreted through the feces. Alterations in the expression of co-transporters on the luminal brush border membrane and microvilli of the small intestine determine the rate of phosphate reabsorption. Parathyroid Hormone (PTH) and a diet high in phosphate result in the endocytosis of these transporters, thus leading to decreased absorption and phosphaturia. PTH binds to specific receptors in the basolateral membrane resulting in the activation of a protein kinase a pathway that leads to phosphorylation of the sodium hydrogen exchange regulatory factor I (NHERF-1), which plays a role in transcriptional regulation of NaPi-IIa. The dissociation of NHERF-1/ NaPi-IIa results in endocytosis of NaPi-IIa and decreased reabsorption of phosphate. On the other hand, PTH deficiency and a diet low in phosphate lead to the insertion of transporters in the membrane, Journal of Nephrology & Therapeutics Citation: Raina R, Garg G, Sethi SK, Schreiber MJ, Simon JF, et al. (2012) Phosphorus Metabolism. J Nephrol Therapeutic S3:008. doi:10.4172/21610959.S3-008