Phosphate homeostasis
Editor-In-Chief: Henry A. Hoff
Overview
In the extracellular region near the plasma membrane, portions of membrane-associated molecules wait to capture phosphate and transport it into the cell. The phosphate may occur as inorganic orthophosphate particles or be part of an organic molecule. Bringing phosphate in any form into the cell and when needed transporting phosphate out of the cell is a necessary activity of phosphate homeostasis for that cell.
Homeostasis
Homeostasis is a relatively stable state of equilibrium or a tendency toward such a state of an open or closed system, especially a living organism. An organism that can regulate its internal environment so as to maintain equilibrium has the property of homeostasis.
Phosphate
A phosphate can occur as a salt of phosphoric acid or an ester of phosphoric acid (an organophosphate). Phosphates are found pervasively in biology. Phosphorus (as phosphate usually) is an essential macromineral for plants, which is studied extensively in soil conservation in order to understand plant uptake from soil systems. In ecological terms, phosphorus is often a limiting nutrient in many environments; i.e. the availability of phosphorus governs the rate of growth of many organisms. In ecosystems an excess of phosphorus can be problematic, especially in aquatic systems, see eutrophication and algal blooms.
Inside a cell, phosphate may be structural to a nucleic acid or phospholipid, form high-energy ester bonds (e.g., in adenosine triphosphate), or participate in signaling.
Outside the cell, phosphate may be dissolved in extracellular fluid (ECF) or form structures such as bone and teeth.
Extracellular fluid (ECF)
Extracellular fluid usually denotes all body fluid outside of cells. It is frequently contained within organs. The skin, for example, is an organ often referred to as the largest organ of the human body as it covers the body, appearing to have the largest surface area of all the organs. But it is a major container for ECF and other organs. ECF includes interstitial fluid (ISF) and transcellular fluid (TCF).
Cardiovascular systems are usually closed, meaning that the blood never leaves the network of blood vessels. In contrast, oxygen and nutrients diffuse across the blood vessel layers and enter interstitial fluid (ISF), which carries oxygen and nutrients to cells, and carbon dioxide and wastes in the opposite direction. Also, the digestive system, which contains TCF, works with the cardiovascular system to provide the nutrients the system needs to keep a heart, when present, pumping.
Blood
Blood is a specialized body fluid contained within the cardiovascular system that is composed of blood cells suspended in plasma. A slight increase of pH in blood plasma above 7.4 causes precipitation of calcium phosphate and resulting turbidity, whereas, in the case of blood serum (plasma without proteins) of the same inorganic composition, the pH may vary fairly widely without precipitation occurring.[1]
It is the proteins that tend to keep calcium salts in solution or at least in suspension.[1] Blood serum is supersaturated with tricalcium phosphate from about pH 6.8 up to about pH 9.25, with a maximum dissolution at pH 7.3.[1] The stability of calcium phosphate in suspension may be improved by reduction of phosphate ion in proportion to calcium in the mixture. With increasing alkalinity above pH 6.3 monocalcium phosphate is converted into dicalcium phosphate. At about pH 6.7 tricalcium phosphate begins to form yet remains in suspension in the presence of proteins.
Hydroxide ions and protein exert antagonistic effects on the suspension of tricalcium phosphate so that with increasing alkalinity the size of the suspension depends on the protein concentration present. Increasing serum concentration decreases turbidity. Protein exerts an inhibitory effect on the precipitation of calcium phosphate both by holding it in solution against other physical factors and by supporting it in suspension.[1]
Phosphate in
A low dietary inorganic phosphate (Pi) intake can lead to an almost 100% absorption of filtered Pi, whereas a high dietary Pi intake leads to a decreased Pi absorption.[2] These changes can occur independent of changes in the ECF concentration of different phosphaturic hormones.[2]
In the upper small intestine Vitamin D3 stimulates Pi cotransport.[2]
Growth hormone, at least in part mediated by insulin-like growth factor I (IGF-I), stimulates Pi cotransport.[2] Thyroid hormone stimulates Pi absorption via a specific increase in Pi cotransport.[2]
Phosphaturic factors reduce the expression of Pi transporters or cotransporters in the cell membrane.[3]
Insulin enhances Pi absorption by stimulation of Pi cotransport and prevents the phosphaturic action of parathyroid hormone (PTH).[2] Calcitonin reduces membrane Pi cotransport in a PTH- and cAMP-independent manner.[2]
Some factors that increase Pi absorption increase the number of the transporters or cotransporters in the cell membrane.[3] Knowledge of the mechanisms that control transporter expression and membrane retrieval of the transporters is essential to understanding how Pi homeostasis is achieved.[3]
Physiological regulation of Pi absorption involves, as far as they have been studied at the molecular level, an altered expression of cotransporter protein that is related most cases to changes in the maximum velocity (Vmax) of Pi cotransport activity.[2]
Phosphate out
Under normal or steady-state physiological conditions, urinary Pi excretion corresponds roughly to phosphate intake in the gastrointestinal tract, mainly via the upper small intestine.[2] To fulfill Pi homeostasis, i.e., keeping extracellular Pi concentration within a narrow range, urinary Pi excretion is under strong physiological control.[2] In contrast to intestinal Pi absorption, which adjusts rather slowly, renal Pi excretion can adjust very rapidly to altered physiological conditions.[2]
Parathyroid hormone (PTH) induces phosphaturia by inhibiting Pi cotransport activity.[2] Glucocorticoids increase phosphate excretion by an inhibition of membrane Pi cotransport, independent of an increase in PTH.[2]
Stanniocalcin 2 (STC2) may suppress Pi cotransport.[2]
References
- ↑ 1.0 1.1 1.2 1.3 Joseph Csapo (1927). "The Influence of Proteins on the Solubility of Calcium Phosphate". J Biol Chem. 75 (2): 509–15.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 Murer H, Hernando N, Forster I, Biber J (2000). "Proximal tubular phosphate reabsorption: molecular mechanisms". Physiol Rev. 80 (4): 1373–409. PMID 11015617. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 3.2 Hernando N, Gisler SM, Pribanic S, Déliot N, Capuano P, Wagner CA, Moe OW, Biber J, Murer H (2005). "NaPi-IIa and interacting partners". J Physiol. 567 (1): 21–6. doi:10.1113/jphysiol.2005.087049. PMID 15890704. Unknown parameter
|month=ignored (help)