Page last updated: 2024-10-24

sodium-dependent phosphate transport

Definition

Target type: biologicalprocess

The directed movement of phosphate into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore, by a mechanism dependent upon sodium ions. [GOC:BHF, GOC:jl]

Sodium-dependent phosphate transport is a crucial process that enables cells to absorb and utilize inorganic phosphate (Pi), a vital component of essential biological molecules like ATP, DNA, and RNA. This transport system is primarily mediated by a family of transmembrane proteins known as sodium-phosphate cotransporters (NaPi). These cotransporters utilize the electrochemical gradient of sodium ions (Na+) to drive the uptake of Pi against its concentration gradient. The process typically involves the following steps:

1. **Binding of Na+ and Pi:** NaPi cotransporters possess binding sites for both Na+ and Pi on their extracellular surface. The binding of Na+ to these sites initiates a conformational change in the transporter, creating a high-affinity binding site for Pi.
2. **Cotransport:** Once Pi binds, the transporter undergoes another conformational change, allowing both Na+ and Pi to move across the cell membrane. This simultaneous movement of Na+ and Pi is driven by the electrochemical gradient of Na+, which is maintained by the Na+/K+ ATPase pump.
3. **Release of Na+ and Pi:** On the intracellular side of the membrane, Na+ and Pi are released from the transporter. The release of Na+ is facilitated by the lower intracellular Na+ concentration. Pi is then available for intracellular metabolic processes.

The NaPi cotransporter family comprises several isoforms, each with distinct tissue distribution and kinetic properties. For instance, NaPi-IIa is highly expressed in the proximal tubules of the kidneys, playing a critical role in renal phosphate reabsorption. NaPi-IIb is predominantly found in the intestines, mediating dietary phosphate absorption.

Sodium-dependent phosphate transport is subject to complex regulation by various factors, including hormonal signals, dietary phosphate intake, and intracellular phosphate levels. For example, the hormone parathyroid hormone (PTH) promotes phosphate excretion by reducing the activity of NaPi cotransporters in the kidneys. Conversely, vitamin D increases phosphate absorption in the intestines by upregulating the expression of NaPi cotransporters.

Dysregulation of sodium-dependent phosphate transport can lead to various pathological conditions. For instance, mutations in NaPi genes can result in inherited disorders of phosphate metabolism, such as hypophosphatemic rickets and osteomalacia. Conversely, excessive phosphate retention due to impaired NaPi transporter function can contribute to hyperphosphatemia, a condition associated with increased risk of cardiovascular disease and kidney stones.'
"

Proteins (1)

ProteinDefinitionTaxonomy
Sodium-dependent phosphate transport protein 2BA sodium-dependent phosphate transport protein 2B that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95436]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
crizotinibcrizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.
3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amineantineoplastic agent;
biomarker;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
pf-06463922lorlatinib : A cyclic ether that is 16,17-dihydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecin-15(10H)-one substituted by methyl groups at positions 2 and 10R, and by cyano, amino and fluoro groups at positions 3, 7 and 12 respectively. It is a small molecule inhibitor of ALK and ROS1 kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer.

lorlatinib: inhibits both anaplastic lymphoma kinase and c-ros oncogene 1 (ROS1) protein
aminopyridine;
aromatic ether;
azamacrocycle;
benzamides;
cyclic ether;
monofluorobenzenes;
nitrile;
organic heterotetracyclic compound;
pyrazoles
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor