ABSTRACT
Inorganic phosphate (Pi) is fundamental to cellular metabolism and, in vertebrates, to skeletal mineralization. To accomplish these functions, transport systems evolved to permit the efficient transfer of negatively charged Pi ions across hydrophobic membranes. Ingested Pi is absorbed by the small intestine, deposited in bone, and filtered
6.1 Introduction .................................................................................................. 137 6.2 Phosphate Homeostasis ................................................................................ 138
6.2.1 Distribution and Chemistry .............................................................. 138 6.2.2 Extracellular Phosphate Homeostasis ............................................... 138 6.2.3 Intestinal Phosphate Reabsorption ................................................... 141
6.3 Renal Phosphate Absorption......................................................................... 141 6.3.1 Physiology and Tubular Localization ............................................... 141
6.3.1.1 Proximal Tubules ............................................................... 143 6.3.1.2 Henle’s Loop, Distal Convoluted Tubules, and
Connecting Tubules ........................................................... 143 6.3.1.3 Collecting Tubules ............................................................. 143
6.3.2 Cellular and Molecular Aspects ....................................................... 143 6.3.2.1 Effect of NPT2a and NPT2c Gene Disruption .................. 145
6.3.3 Regulation of Renal Phosphate Transport ........................................ 145 6.3.3.1 Dietary Phosphate .............................................................. 146 6.3.3.2 Parathyroid Hormone ......................................................... 147 6.3.3.3 Fibroblast Growth Factor 23 .............................................. 148 6.3.3.4 Klotho ................................................................................ 149 6.3.3.5 Other Hormonal Regulators ............................................... 150 6.3.3.6 Non-Hormonal Regulators ................................................. 151
6.4 Disorders of Phosphate Homeostasis ............................................................ 152 6.4.1 Genetic and Acquired Human Disorders ......................................... 152 6.4.2 Chronic Kidney Disease (CKD) ....................................................... 153
References .............................................................................................................. 156
by the kidney where it is reabsorbed and excreted in amounts determined by the specific organism. The kidney is a major determinant of Pi homeostasis due to its ability to increase or decrease its Pi reabsorptive capacity to accommodate Pi need. Recent significant advances have been made in our understanding of the molecular mechanisms involved in renal tubular Pi reabsorption and its hormonal regulation and modulation by dietary Pi intake. This chapter describes the mechanisms regulating Pi homeostasis and the cellular and molecular aspects of renal Pi transport and their regulation.
