Phosphate homeostasis: Difference between revisions
(→Bone) |
|||
| Line 92: | Line 92: | ||
==[[Bone]]== | ==[[Bone]]== | ||
During [[bone resorption]] high levels of phosphate are released into the ECF as | During [[bone resorption]] high levels of phosphate are released into the ECF as [[osteoclast]]s tunnel into mineralized bone, breaking it down and releasing phosphate, that results in a transfer of phosphate from bone fluid to the blood. During [[Child development|childhood]], bone formation exceeds resorption, but as the [[Ageing|aging process]] occurs, resorption exceeds formation. | ||
=References= | =References= | ||
Revision as of 03:47, 21 April 2009
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.
Orthophosphate (Pi)
Pi occurs in blood, blood plasma and blood serum.[1]
Pyrophosphate (PPi)
PPi occurs in synovial fluid, plasma, and urine at levels sufficient to block calcification and may be a natural inhibitor of hydroxyapatite formation in ECF.[2]
Blood
Blood is a specialized body ECF contained within the cardiovascular system that is composed of blood cells suspended in plasma.
Orthophosphate
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 clotting 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]
Pyrophosphate
Blood plasma levels of PPi in normal human children can range from approximately 300-700 pmol/µg protein.[3]
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.[4] These changes can occur independent of changes in the ECF concentration of different phosphaturic hormones.[4]
In the upper small intestine Vitamin D3 stimulates Pi cotransport.[4]
Growth hormone, at least in part mediated by insulin-like growth factor I (IGF-I), stimulates Pi cotransport.[4] Thyroid hormone stimulates Pi absorption via a specific increase in Pi cotransport.[4] Stanniocalcin 1 (STC1) stimulates membrane Pi cotransport.[4]
Phosphaturic factors reduce the expression of Pi transporters or cotransporters in the cell membrane.[5]
Insulin enhances Pi absorption by stimulation of Pi cotransport and prevents the phosphaturic action of parathyroid hormone (PTH).[4] Calcitonin reduces membrane Pi cotransport in a PTH- and cAMP-independent manner.[4]
Some factors that increase Pi absorption increase the number of the transporters or cotransporters in the cell membrane.[5] Knowledge of the mechanisms that control transporter expression and membrane retrieval of the transporters is essential to understanding how Pi homeostasis is achieved.[5]
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.[4]
Phosphate out
Orthophosphate
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.[4] To fulfill Pi homeostasis, i.e., keeping extracellular Pi concentration within a narrow range, urinary Pi excretion is under strong physiological control.[4] In contrast to intestinal Pi absorption, which adjusts rather slowly, renal Pi excretion can adjust very rapidly to altered physiological conditions.[4] Specifically, membrane Pi cotransporter protein content, and thus Pi absorption, responds within hours to alterations in dietary Pi intake.[4]
Parathyroid hormone (PTH) induces phosphaturia by inhibiting Pi cotransport activity.[4] Glucocorticoids increase phosphate excretion by an inhibition of membrane Pi cotransport, independent of an increase in PTH.[4]
Stanniocalcin 2 (STC2) may suppress Pi cotransport.[4]
Pyrophosphate
Cells may channel intracellular PPi into ECF.[3] ANK is a nonenzymatic plasma-membrane PPi channel that supports extracellular PPi levels.[3] Defective function of the membrane PPi channel ANK is associated with low extracellular PPi and elevated intracellular PPi.[2] Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) may function to raise extracellular PPi.[3]
Phosphate reserves
PPi-generating nucleoside triphosphate pyrophosphohydrolase (EC 3.1.4.1) activities of a group of ecto-enzymes in the phosphodiesterase nucleotide pyrophosphatase (PDNP) family have been recognized to contribute to the regulation of intracellular and extracellular PPi levels in several tissues.[3]
Intracellular phosphate
Although ENPP3 regulates intracellular PPi concentrations it does not seem to significantly regulate extracellular PPi.[3]
Extracellular phosphate
PPi inhibits hydroxyapatite deposition in bone and cartilage.[3] Many studies have shown that PPi is a potent inhibitor of calcification, bone mineralization, and bone resorption.[2] Human defects in alkaline phosphatase, an enzyme that degrades PPi, lead to an increase in PPi levels and a severe block in skeletal mineralization.[2] Genetic defects in a cell surface ectoenzyme that normally generates extracellular PPi from nucleotide triphosphate cause ectopic mineralization of joints and ligaments and may be associated with spinal ligament ossification in humans.[2]
Bone
During bone resorption high levels of phosphate are released into the ECF as osteoclasts tunnel into mineralized bone, breaking it down and releasing phosphate, that results in a transfer of phosphate from bone fluid to the blood. During childhood, bone formation exceeds resorption, but as the aging process occurs, resorption exceeds formation.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Joseph Csapo (1927). "The Influence of Proteins on the Solubility of Calcium Phosphate". J Biol Chem. 75 (2): 509–15.
- ↑ 2.0 2.1 2.2 2.3 2.4 Ho AM, Johnson MD, Kingsley DM (2000). "Role of the mouse ank gene in control of tissue calcification and arthritis". Science. 289 (5477): 265–70. doi:10.1126/science.289.5477.265. PMID 10894769. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Rutsch F, Vaingankar S, Johnson K, Goldfine I, Maddux B, Schauerte P, Kalhoff H, Sano K, Boisvert WA, Superti-Furga A, Terkeltaub R (2001). "PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification". Am J Pathol. 158 (2): 543–54. PMID 11159191. Unknown parameter
|month=ignored (help) - ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 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) - ↑ 5.0 5.1 5.2 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)