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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 (organophosphate). 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.

Introduction

Due to its high reactivity, phosphorus is never found as a free element in nature. Phosphates are found pervasively in biology. Phosphate is a component of DNA and RNA and an essential element for all living cells. Phosphate metabolism is the complete set of phosphate chemical reactions that occur in living cells. Phosphorus (as phosphate usually) is often a limiting nutrient in many environments; i.e. the availability of phosphorus governs the rate of growth of many organisms. Living cells also use phosphate to transport cellular energy via adenosine triphosphate (ATP). Nearly every cellular process that uses energy obtains it in the form of ATP. 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.

In medicine, low phosphate syndromes are caused by malnutrition, by failure to absorb phosphate, and by metabolic syndromes which draw phosphate from the blood or pass too much of it into the urine. All are characterized by hypophosphatemia (see article for medical details). Symptoms of low phosphate include muscle and neurological dysfunction, and disruption of muscle and blood cells due to lack of ATP.

In ecosystems an excess of phosphorus can be problematic, especially in aquatic systems, see eutrophication and algal blooms.

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. An organism that can regulate its internal environment so as to maintain equilibrium has the property of homeostasis. ATP is important for phosphorylation, a key regulatory event in cells.

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.

Phosphate metabolism

With respect to the complete set of phosphate chemical reactions that occur in living cells, there are approximately 1385 such reactions.^[1] Indeed, concerning polyphosphate there are approximately 10 such reactions.^[2]

In pyrimidine metabolism, EC 3.6.1.2 (trimetaphosphatase) can convert trimetaphosphate into triphosphate per the reaction:

trimetaphosphate + H₂O <=> triphosphate (ultimately leading to the production of 2'-Deoxy-5-hydroxy-methylcytidine-5'-triphosphate).^[3]

Trimetaphosphatase activity has been found to be localized in the mouse testis during acrosomal formation.^[4] Osteoclasts secrete trimetaphosphatase towards the resorbing bone surfaces.^[5]

Phosphate bioenergetics

Bioenergetics concerns energy flow through living systems. This area of biological research includes the study of cellular processes such as cellular respiration that can lead to production and utilization of energy in forms such as ATP molecules. Living cells use phosphate to transport cellular energy via nucleotides such as adenosine triphosphate (ATP). Nearly every cellular process that uses energy obtains it in the form of ATP.

Protons in aqueous solution function in the production of ATP in cell organelles such as mitochondria^[6]. Other cellular sources of ATP such as glycolysis for direct coupling of enzyme activity to ATP production are not the major source of useful chemical energy in most cells. Chemiosmotic coupling is the major energy producing process in most cells, being utilized in chloroplasts and many single celled organisms in addition to mitochondria.

Structural phosphate

Inside a cell, phosphate may be structural to a nucleic acid such as DNA and RNA or phospholipid. Outside the cell, phosphate may be dissolved in extracellular fluid (ECF) or form structures such as bone and teeth. Bringing phosphate in any form into the cell from a phosphate containing structure or for such a structure and when needed transporting phosphate out of the cell perhaps to a structure is a necessary activity of phosphate homeostasis for that cell.

Signaling

Lipid signaling involves G-protein coupled receptors to which lysophosphatidic acid (LPA) binds, through which sphingosine-1-phosphate (S1P) acts, and platelet-activating factor (PAF) signals. The key event of diacylglycerol (DAG) signaling is the hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2) to DAG and inositol triphosphate (IP3). IP3 is soluble and diffuses freely into the cytoplasm. It can be recognised by the inositol triphosphate receptor (IP3R). IP3 contributes to the activation of protein kinase C (PKC).^[7]^[8]

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.

Phosphatidate

Lysophosphatidic acid (LPA) is an intermediate in the synthesis of phosphatidic acid (PA). ENPP2 functions as a phospholipase, which catalyzes the transformation of lysophosphatidylcholine into LPA in ECF.^[9] LPA has been detected in plasma, ascitic fluid, follicular fluid, and aqueous humor.^[9]

ECF Orthophosphate (P_i)

The level of inorganic orthophosphate (P_i) is tightly balanced inside the cell and in the whole vertebrate organism.^[10] The concentration of free P_i is balanced in the millimolar range in ICF and ECF.^[10] Bacteria, yeast, plants, and vertebrates have developed their own strategies to control P_i homeostasis.^[10] The daily need for P_i is covered by intestinal absorption from the diet, the major storage compartment is bone, and the metabolic and structural intracellular need is met in part by phosphate cotransporters.^[10] The ECF concentration of P_i is controlled by tightly regulating renal excretion.^[10] Principal properties of mammalian renal P_i reabsorption are pH-dependency, regulation by parathyroid hormone (PTH), and P_i availability.^[10] These properties are expressed by SLC34A1-3 (sodium-dependent phosphate transporter 2, NPT2), whereas NPT3 (SLC17A2) mediates Na⁺-dependent P_i transport.^[10] NPT1 (SLC17A1) does not have a prominent role in regulating body P_i homeostasis.^[10] Insulin stimulates NPT1 expression and Na⁺/P_i uptake which is reversed by glucagon.^[10] NPT3 may have a housekeeping role at the cellular level per its broad range of expression and its ability to adapt to changes in extracellular P_i concentration.^[10] The expression of NPT3 is compatible with the presence of other NPT.^[10] Members of the NPT1 family are linked with insulin-stimulated glucose metabolism.^[10] NPT2 in the kidney and small intestine are responsible for intracellular P_i accumulation in order to establish a transepithelial flux of P_i.^[10] NPT4 (SLC17A3) is expressed in the small intestine, kidney, liver, and testis.^[11]

ECF Pyrophosphate (PP_i)

PP_i occurs in synovial fluid, plasma, and urine at levels sufficient to block calcification and may be a natural inhibitor of hydroxyapatite formation in ECF.^[12]

Blood

Blood is a specialized body ECF contained within the cardiovascular system that is composed of blood cells suspended in plasma. Its phosphate content is in many forms. Per the list of human blood components: adenosine triphosphate (ATP) concentration in whole blood is 3.1-5.7 x 10^-4 g/cm³, which is the equivalent of 5-10 x 10^-5 g/cm³ of phosphorus; diphosphoglycerate is 8-16 x 10^-5 g/cm³; cGMP is 0.6-4.4 x 10^-9 g/cm³; hexosephosphate P is 1.4-5 x 10^-5 g/cm³ (0-2 x 10^-6 g/cm³ in plasma or serum); DNA is 0-1.6 x 10^-5 g/cm³ in plasma or serum; phospholipid is 2.25-2.85 x 10^-3 g/cm³ (5-12 x 10^-5 g/cm³ in plasma or serum); pyrimidine nucleotide is 2.6-4.6 x 10^-5 g/cm³ (2-12 x 10^-7 g/cm³ in plasma or serum); and RNA is 5-8 x 10^-4 g/cm³ (4-6 x 10^-5 g/cm³ in plasma or serum). P_i occurs in blood, blood plasma and blood serum.^[13] The total phosphorus content is 2-3.9 x 10^-5 g/cm³ as inorganic phosphate and 3.5-4.3 x 10^-4 g/cm³ total (2.3-4.5 x 10^-5 g/cm³ and 1-1.5 x 10^-4 g/cm³ in plasma or serum, respectively).

Blood 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.^[13]

It is the proteins that tend to keep calcium salts in solution or at least in suspension.^[13] 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.^[13] 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.^[13]

Blood Pyrophosphate

Blood plasma levels of PP_i in normal human children can range from approximately 300-700 pmol/µg protein.^[14]

Phosphate in

Bringing phosphate in any form into a cell possibly from a phosphate containing structure, for such a structure, or whatever the need, may require phagocytosis, endocytosis, or a phosphate-importing protein or symporter.

EC 3.6.3.20 is a phosphate-importing enzyme that catalyzes the chemical reaction

ATP + H₂O + glycerol-3-phosphateout <=> ADP + phosphate + glycerol-3-phosphatein.

EC 3.6.3.27 is a phosphate-importing enzyme that catalyzes the chemical reaction

ATP + H₂O + phosphateout <=> ADP + phosphate + phosphatein.

Orthophosphate in

Growth hormone, at least in part mediated by insulin-like growth factor I (IGF-I), stimulates P_i cotransport.^[15] Thyroid hormone stimulates P_i absorption via a specific increase in P_i cotransport.^[15] Stanniocalcin 1 (STC1) stimulates membrane P_i cotransport.^[15]

Phosphaturic factors reduce the expression of P_i transporters or cotransporters in the cell membrane.^[16]

Insulin enhances P_i absorption by stimulation of P_i cotransport and prevents the phosphaturic action of parathyroid hormone (PTH).^[15] Calcitonin reduces membrane P_i cotransport in a PTH- and cAMP-independent manner.^[15]

Some factors that increase P_i absorption increase the number of the transporters or cotransporters in the cell membrane.^[16] Knowledge of the mechanisms that control transporter expression and membrane retrieval of the transporters is essential to understanding how P_i homeostasis is achieved.^[16]

Physiological regulation of P_i absorption involves, as far as it has been studied at the molecular level, an altered expression of cotransporter protein that is related in most cases to changes in the maximum velocity (V_max) of P_i cotransport activity.^[15]

ISF P_i absorption

PiT1 is likely to be a major carrier of phosphate from ISF into most cell types.^[17] V_max can go approximately from 39 to 121, with ISF phosphate to phosphate-free ISF.^[17] Mammaliam cell internal phosphate levels (75 milliequivalents per liter) are maintained at higher levels than ISF (4 milliequivalents per liter) in opposition to an electrochemical gradient that favors phosphateout.^[17]

Low ECF P_i levels can result in upregulated PiT1 and PiT2 expression in mammalian cells.^[18] PiT1 and PiT2 exhibit positve cooperative P_i uptake. PiT2 supports Na⁺-independent P_i uptake.^[18] Ca²⁺ or Ca²⁺ and Mg²⁺ increase PiT1- and PiT2-mediated NaP_i import.^[18] V_max for PiT1 and PiT2 are approximately 453 and 450 pmol·cell^-1·h^-1, respectively.^[18] The average P_i uptake for PiT2 and PiT1 at pH 7.5 is approximately 118 and 115 pmol·cell^-1·h^-1, respectively.^[18] P_i transport has similar average P_i uptake at different pH values: 5.5 to 8.5.^[18] The Na⁺-independent P_i uptake of PiT2 is in acidic ECF conditions.^[18] With physiological Na⁺ concentration in the human body in the range of 130–145 mM, there is always plenty to sustain P_i uptake via PiT1 and PiT2.^[18]

Small intestine P_i absorption

A low dietary inorganic phosphate (P_i) intake can lead to an almost 100% absorption of filtered P_i, whereas a high dietary P_i intake leads to a decreased P_i absorption.^[15] These changes can occur independent of changes in the ECF concentration of different phosphaturic hormones.^[15]

In the upper small intestine Vitamin D₃ stimulates P_i cotransport.^[15] Matrix extracellular phosphoglycoprotein (MEPE), a phosphatonin, promotes phosphaturia.^[19] Short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum.^[19] The short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurs without any changes in circulating levels of parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, or fibroblast growth factor 23 (FGF23).^[19] MEPE may be involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract.^[19]

Renal P_i reabsorption

NPT2 dominates in renal P_i reabsorption, which is exclusive under non-pathological conditions in the mammalian kidney.^[10] Na⁺ interacts in a cooperative way with NPT2 with a stoichiometry of 3Na⁺ to 1P_i.^[10] Protons (H⁺) decrease the affinity of NPT2 for Na⁺.^[10]

There is a link between the action of PTH, P_i availability, and renal cell membrane integration/retrieval of NPT2.^[10] Changes in dietary P_i content have a major regulatory effect on P_i reabsorption.^[20] Dietary P_i restriction is associated with an adaptive increase of the overall capacity for P_i uptake mediated by an increase of V_max of sodium gradient-dependent phosphate transport.^[20] In response to chronic (8 day) dietary P_i restriction, the adaptive increase in sodium-P_i cotransport activity is associated with parallel increases in NPT2 and its mRNA abundances.^[20] However, in response to acute (2 h) dietary P_i restriction, the rapid adaptive increase in sodium-P_i cotransport activity is associated with parallel increases in NPT2, but without change in its mRNA abundance.^[20]

The role of intracellular NPT2 in the rapid adaptation to dietary P_i is correlated with the localization of the Golgi membrane protein 58 kDa and the lysosomal membrane glycoprotein Igp120, as follows^[20]: after chronic adaptation to a high P_i diet, NPT2 is in the subcell membrane portion and perinuclear region where in part it spatially coincides with the Golgi-like compartment but not with the lysosomal compartment. Acute adaptation from a high P_i diet to low P_i leads to depletion of intracellular NPT2, with NPT2 only in the Golgi-like compartment. After chronic adaptation to a low P_i diet, intracellular NPT2 is predominantly localized in the region of the Golgi-like compartment and additional sub cell membrane and central cell portions, with minimal localization to Igp120. Acute adaptation from a low P_i to a high P_i diet leads to increased abundance of intracellular NPT2 in the sub cell membrane and central portions, with considerable spatial localization to the lysosomal compartment.

The chronic adaptive response to a low P_i diet is characterized by an increase in NPT2 mRNA abundance.^[20]

Role of microtubules

In the presumable rapid translocation of NPT2 in response to acute administratiion of a low P_i diet, microtubules (tubulin) are involved with upregulation of NPT2 activity and translocation from intracellular compartments in the vicinity of the nucleus to the cell membrane, but uninvolved in NPT2 expression.^[20] Regarding response to an acute administration of a high P_i diet after chronic administration of a low P_i, microtubules are not involved in rapid downregulation of NPT2 activity or NPT2 abundance.^[20]

The rapid adaptive increase in sub cell membrane NPT2 with chronic feeding of a high P_i diet, after an acute administration of a low P_i diet, is probably mediated by translocation of presynthesized NPT2 to this portion by microtubule-dependent mechanisms.^[20]

The targeting of NPT2 to the cell membrane seems to be dependent on the microtubule network.^[20]

Role of microfilaments

Microfilaments (actin cytoskeleton) may play a central role in the rapid downregulation of Na⁺-P_i cotransport.^[20] The dependence of endocytosis on intact microfilaments in polarized epithelial cells has been demonstrated.^[20]

Organophosphates in

Phosphatidic acid phosphatases (PAPs) transport phosphatidic acid (PA), lysophosphatidic acid (LPA), ceramide 1-phosphate (C1P), and sphingosine 1-phosphate (S1P) from ECF through the plasma membrane at different V_max.^[21] Once inside the cell, these PAPs (PPAP2A, PPAP2B, and PPAP2C) hydrolyze each phosphate per EC 3.1.3.4:

a 3-sn-phosphatidate + H₂O <=> a 1,2-diacyl-sn-glycerol + P_i.

PPAP2A displays comparable V_max values for all four substrates, with highest activity for LPA and PA. PPAP2B shows a similarly higher relative V_max activity with LPA, while PPAP2C displays significantly higher activity with S1P.^[21] For some cells PPAP2A may be an ectoenzyme that dephosphorylates PA to form diacylglycerol (DG) prior to DG transport into the cell.^[21]

Phosphate exchange

Glycerol phosphate transporter (GlpT) transports glycerol-3-phosphate (G3P) into the cytoplasm and P_i into the periplasm.^[22] While GlpT transports between cellular compartments through internal membranes, it can also transport across the cell membrane.^[23] GlpT functions for G3P uptake and is driven by a P_i gradient. Periplasmic (or ISF) release of P_i allows its replacement in the substrate-binding site by G3P, which has a higher affinity; on the cytoplasmic side of the membrane, P_i replaces G3P because of its higher cytosolic concentration.^[22]

Phosphate out

Orthophosphate out

Under normal or steady-state physiological conditions, urinary P_i excretion corresponds roughly to phosphate intake in the gastrointestinal tract, mainly via the upper small intestine.^[15] To fulfill P_i homeostasis, i.e., keeping extracellular P_i concentration within a narrow range, urinary P_i excretion is under strong physiological control.^[15] In contrast to intestinal P_i absorption, which adjusts rather slowly, renal P_i excretion can adjust very rapidly to altered physiological conditions.^[15] Specifically, membrane P_i cotransporter protein content, and thus P_i absorption, responds within hours to alterations in dietary P_i intake.^[15]

Parathyroid hormone (PTH) induces phosphaturia by inhibiting P_i cotransport activity.^[15] Glucocorticoids increase phosphate excretion by an inhibition of membrane P_i cotransport, independent of an increase in PTH.^[15]

Stanniocalcin 2 (STC2) may suppress P_i cotransport.^[15]

Pyrophosphate out

Cells may channel intracellular PP_i into ECF.^[14] ANK is a nonenzymatic plasma-membrane PP_i channel that supports extracellular PP_i levels.^[14] Defective function of the membrane PP_i channel ANK is associated with low extracellular PP_i and elevated intracellular PP_i.^[12] Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) may function to raise extracellular PP_i.^[14]

Phosphate reserves

A well-fed adult in the industrialized world consumes and excretes about 1-3 g of phosphorus per day in the form of phosphate. Per the elemental composition of the "standard man" of 70 kg, phosphorus is 780 g or 1.1%.^[24] Of this 1.4 g/kg is present in soft tissue with the remainder in mineralized tissue such as bone and teeth.^[25] Only about 0.1% of body phosphate circulates in the blood, but this amount reflects the amount of phosphate available to soft tissue cells. Blood plasma contains orthophosphate (as HPO₄^2-) and H₂PO₄^1- in the ratio of about 4:1.^[25]

The total quantity of ATP in the human body is about 0.1 mole. This ATP is constantly being broken down into ADP, and then converted back into ATP. At any given time, the total amount of ATP + ADP remains fairly constant. The energy used by human cells requires the hydrolysis of 100 to 150 moles of ATP daily which is around 50 to 75 kg. Typically, a human will use up their body weight of ATP over the course of the day.^[26] This means that each ATP molecule is recycled 1000 to 1500 times daily, or about once every minute.

PP_i-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 PP_i levels in several tissues.^[14]

Intracellular phosphate

With the number of cells in the human body of 10-100 trillion or 10¹³ to 10¹⁴, there are approximately 29-290 x 10⁹ atoms of phosphorus per cell or a concentration on the order of 10^-3 units of phosphorus probably as phosphate per cell. As computer simulation has shown the probability of finding a target decreases rapidly with distance and becomes <1% when the starting distance exceeds the target's 10-fold radius,^[27] which by assumption of a simple spherical volume would put the target's concentration on the order of 10^-3.

Although ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) regulates intracellular PP_i concentrations it does not seem to significantly regulate extracellular PP_i.^[14]

Extracellular phosphate

PP_i inhibits hydroxyapatite deposition in bone and cartilage.^[14] Many studies have shown that PP_i is a potent inhibitor of calcification, bone mineralization, and bone resorption.^[12] Human defects in alkaline phosphatase, an enzyme that degrades PP_i, lead to an increase in PP_i levels and a severe block in skeletal mineralization.^[12] Genetic defects in a cell surface ectoenzyme that normally generates extracellular PP_i from nucleotide triphosphate cause ectopic mineralization of joints and ligaments and may be associated with spinal ligament ossification in humans.^[12]

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.

Phosphate regulation

An organism that can regulate its internal environment so as to maintain equilibrium has the property of homeostasis. ATP is important for phosphorylation, a key regulatory event in cells.

Fibroblast growth factor 23 (FGF23) is essential for maintaining phosphate homeostasis. Klotho is integral to the plasma membrane^[28] and essential for endogenous FGF23 function^[29]. FGF23 regulates NPT2a independent of parathyroid hormone (PTH) and serum 1,25-dihydroxyvitamin D level by controlling renal expressions of key enzymes of vitamin D metabolism.^[30] FGF23 inhibits renal tubular phosphate transport.^[31] The secretion of FGF23 requires O-glycosylation, which is selectively directed by GALNT3, to block processing of FGF23.^[32]

Both NPT2a and NPT2c are regulated in a similar fashion by parathyroid hormone (PTH), FGF23, and dietary phosphate.^[33] Phosphate deprivation increases NPT2a and NPT2c expression.^[33] The relative expression of NPT2a is an order of magnitude higher than that of NPT2c in kidneys of organisms maintained on a normal phosphate diet.^[33] Normal animals exhibit a more robust increase in NPT2c than in NPT2a in response to phosphate deprivation.^[33] NPT2c is regulated by FGF23 and probably downregulated by PTH.

PHEX may regulate FGF23 expression as part of a potential hormonal axis between bone and kidney that controls systemic phosphate homeostasis and mineralization.^[34] PHEX is highly expressed in cartilage, bone, and teeth, where it is present in osteoblasts, osteocytes, and odontoblasts, especially at the transition between the maturation of pre-osteoblasts to mature osteoblasts when PHEX expression is normally up-regulated.^[34]

Phosphate transistasis

The power or tendency of a living thing to keep changing its phosphate needs according to the transformation of circumstances is phosphate transistasis; i.e., to reform its functions to maintain a meaningful condition, by means of multiple dynamic equilibrium adjustments, controlled by interrelated phosphate regulation mechanisms. Homeostasis and transistasis are needed to maintain stability and to survive. An organism has to endure, adapt, and evolve to modifications of the environment. It does this by testing which way its variables should be adjusted, by being ultraflexible.

Negative feedback is a reaction in which the system responds in such a way as to reverse the direction of change. Since this tends to keep things constant, it allows the maintenance of homeostasis.

In positive feedback, the response is to amplify the change in the variable, allowing the maintenance of transistasis.

Mathematical modeling of the rate kinetics of growth and acid phosphatase formation under varying degrees of phosphate limitation is concerned with (a) the time lag for exponential growth, (b) the biphasic growth on a substrate (glucose) and its product, (c) sustained growth on conservative phosphate, and (d) the derepression of acid phosphatase. The numerical calculations using appropriate parametric constants describes the variation in the cell mass, glucose, product, and inorganic phosphate concentrations, and the enzyme activity of acid phosphatase during aerobic growth under different conditions of phosphate starvation. Study by simulation revealed that the optimum initial phosphate concentration in the medium giving a high productivity of acid phosphate is 2.0 mg phosphorus/g glucose liter.^[35]

Phosphate medicine

Low phosphate syndromes are caused by malnutrition, by failure to absorb phosphate, and by metabolic syndromes which draw phosphate from the blood or pass too much of it into the urine. All are characterized by hypophosphatemia (see article for medical details). Symptoms of low phosphate include muscle and neurological dysfunction, and disruption of muscle and blood cells due to lack of ATP.

Hyperphosphoric acid can be added to blood to release CO₂.^[36]

Hyperphosphates (salts or esters) or oleophosphates can result from the use of hyperphosphoric acid. Hyperphosphate, when used to induce hyperphosphatemia, may directly promote calcium deposition and osteocalcin expression.^[37]

Two rare autosomal recessive metabolic disorders characterized by hyperphosphatemia: hyperphosphatemic familial tumoral calcinosis (HFTC) and hyperphosphatemia-hyperostosis syndrome (HHS) appear to be caused by mutations in GALNT3^[38]^[39] which in turn affects FGF23^[32].

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikipedia.

References

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↑ ^9.0 ^9.1 Ferry G, Tellier E, Try A, Grés S, Naime I, Simon MF, Rodriguez M, Boucher J, Tack I, Gesta S, Chomarat P, Dieu M, Raes M, Galizzi JP, Valet P, Boutin JA, Saulnier-Blache JS (2003). "Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity". J Biol Chem. 278 (20): 18162–9. doi:10.1074/jbc.M301158200. PMID 12642576. Unknown parameter |month= ignored (help)
↑ ^10.00 ^10.01 ^10.02 ^10.03 ^10.04 ^10.05 ^10.06 ^10.07 ^10.08 ^10.09 ^10.10 ^10.11 ^10.12 ^10.13 ^10.14 ^10.15 ^10.16 Werner A, Dehmelt L, Nalbant P (1998). "Na+-dependent phosphate cotransporters: the NaPi protein families". J Exp Biol. 201 (Pt 23): 3135–42. PMID 9808829. Unknown parameter |month= ignored (help)
↑ Ruddy DA, Kronmal GS, Lee VK, Mintier GA, Quintana L, Domingo R Jr, Meyer NC, Irrinki A, McClelland EE, Fullan A, Mapa FA, Moore T, Thomas W, Loeb DB, Harmon C, Tsuchihashi Z, Wolff RK, Schatzman RC, Feder JN (1997). "A 1.1-Mb transcript map of the hereditary hemochromatosis locus". 7 (5): 441–56. PMID 9149941. Unknown parameter |month= ignored (help)
↑ ^12.0 ^12.1 ^12.2 ^12.3 ^12.4 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)
↑ ^13.0 ^13.1 ^13.2 ^13.3 ^13.4 Joseph Csapo (1927). "The Influence of Proteins on the Solubility of Calcium Phosphate". J Biol Chem. 75 (2): 509–15.
↑ ^14.0 ^14.1 ^14.2 ^14.3 ^14.4 ^14.5 ^14.6 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)
↑ ^15.00 ^15.01 ^15.02 ^15.03 ^15.04 ^15.05 ^15.06 ^15.07 ^15.08 ^15.09 ^15.10 ^15.11 ^15.12 ^15.13 ^15.14 ^15.15 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)
↑ ^16.0 ^16.1 ^16.2 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)
↑ ^17.0 ^17.1 ^17.2 Kavanaugh MP, Miller DG, Zhang W, Law W, Kozak SL, Kabat D, Miller AD (1994). "Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters". Proc Natl Acad Sci U S A. 91 (15): 7071–5. PMID 8041748. Unknown parameter |month= ignored (help)
↑ ^18.0 ^18.1 ^18.2 ^18.3 ^18.4 ^18.5 ^18.6 ^18.7 Bøttger P, Hede SE, Grunnet M, Høyer B, Klaerke DA, Pedersen L (2006). "Characterization of transport mechanisms and determinants critical for Na+-dependent Pi symport of the PiT family paralogs human PiT1 and PiT2". Am J Physiol Cell Physiol. 291 (6): C1377–87. PMID 16790504. Unknown parameter |month= ignored (help)
↑ ^19.0 ^19.1 ^19.2 ^19.3 Marks J, Churchill LJ, Debnam ES, Unwin RJ (2008). "Matrix extracellular phosphoglycoprotein inhibits phosphate transport". J Am Soc Nephrol. 19 (12): 2313–20. PMID 19005008. Unknown parameter |month= ignored (help)
↑ ^20.00 ^20.01 ^20.02 ^20.03 ^20.04 ^20.05 ^20.06 ^20.07 ^20.08 ^20.09 ^20.10 ^20.11 Lötscher M, Kaissling B, Biber J, Murer H, Levi M (1997). "Role of microtubules in the rapid regulation of renal phosphate transport in response to acute alterations in dietary phosphate content". J Clin Invest. 99 (6): 1302–12. PMID 9077540. Unknown parameter |month= ignored (help)
↑ ^21.0 ^21.1 ^21.2 Roberts R, Sciorra VA, Morris AJ (1998). "Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform". J Biol Chem. 273 (34): 22059–67. PMID 9705349. Unknown parameter |month= ignored (help)
↑ ^22.0 ^22.1 Huang Y, Lemieux MJ, Song J, Auer M, Wang DN (2003). "Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli". Science. 301 (5633): 616–20. PMID 12893936. Unknown parameter |month= ignored (help)
↑ "Major Facilitator Superfamily".
↑ CRC Handbook of Chemistry and Physics (88th ed.). Boca Raton, Florida: CRC Press. 2007–2008. p. 7-18. Unknown parameter |editor-in-chief= ignored (help)CS1 maint: Date format (link)
↑ ^25.0 ^25.1 Schwartz MK. "Phosphate metabolism". McGraw-Hill Encyclopedia of Science & Technology (9th ed.). 13: 343–4.
↑ Buono MJ, Kolkhorst FW (2001). "Estimating ATP resynthesis during a marathon run: a method to introduce metabolism" (PDF). Adv Physiol Educ. 25 (2): 70–1.
↑ Guigas G, Weiss M (2008). "Sampling the Cell with Anomalous Diffusion—The Discovery of Slowness". Biophys J. 94 (1): 90–4. doi:10.1529/biophysj.107.117044. PMID 17827216. Unknown parameter |month= ignored (help)
↑ Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y (1998). "Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein". Biochem Biophys Res Commun. 242 (3): 626–30. PMID 9464267. Unknown parameter |month= ignored (help)
↑ Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T (2006). "Klotho converts canonical FGF receptor into a specific receptor for FGF23". Nature. 444 (7120): 770–4. PMID 17086194. Text "month-Dec " ignored (help)
↑ Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004). "FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis". J Bone Miner Res. 19 (3): 429–35. doi:10.1359/JBMR.0301264. PMID 15040831. Unknown parameter |month= ignored (help)
↑ "Entrez Gene: FGF23 fibroblast growth factor 23".
↑ ^32.0 ^32.1 Kato K, Jeanneau C, Tarp MA, Benet-Pagès A, Lorenz-Depiereux B, Bennett EP, Mandel U, Strom TM, Clausen H (2006). "Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation". J Biol Chem. 281 (27): 18370–7. PMID 16638743. Unknown parameter |month= ignored (help)
↑ ^33.0 ^33.1 ^33.2 ^33.3 Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H (2006). "SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis". Am J Hum Genet. 78 (2): 179–92. PMID 16358214. Unknown parameter |month= ignored (help)
↑ ^34.0 ^34.1 Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD (2003). "Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX". J Biol Chem. 278 (39): 37419–26. doi:10.1074/jbc.M304544200. PMID 12874285. Unknown parameter |month= ignored (help)
↑ Toda K, Yabe I (2004). "Mathematical model of cell growth and phosphatase biosynthesis in Saccharomyces carlsbergensis under phosphate limitation". Biotech Bioeng. 21 (3): 487–502. doi:10.1002/bit.260210310. Unknown parameter |month= ignored (help)
↑ Sidossis LS, Mittendorfer B, Chinkes D, Walser E, Wolfe RR (1999). "Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism". Am J Physiol. 276 ((3 Pt 1)): E427–34. PMID 10070006. Unknown parameter |month= ignored (help)
↑ Lu W, Wang X, Zhao X (2007). "Study of vascular smooth muscle cell calcification induced by hyperphosphate and intervented by phosphonoformic acid". J Nanjing Med Univ. 21 (6): 377–81. doi:10.1016/S1007-4376(07)60082-3. Unknown parameter |month= ignored (help)
↑ Specktor P, Cooper JG, Indelman M, Sprecher E (2006). "Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred". J Hum Genet. 51 (5): 487–90. PMID 16528452.
↑ Ichikawa S, Guigonis V, Imel EA, Courouble M, Heissat S, Henley JD, Sorenson AH, Petit B, Lienhardt A, Econs MJ (2007). "Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations". J Clin Endocrinol Metab. 92 (5): 1943–7. PMID 17311862. Unknown parameter |month= ignored (help)

External links

Template:SIB

Template:WH Template:WS

[phosphatereactions-1] "DBGET Search Result: REACTION phosphate".

[polyphosphatereactions-2] "DBGET Search Result: REACTION polyphosphate".

[trimetaphosphatase-3] "KEGG PATHWAY: Pyrimidine metabolism - Reference pathway (Reaction)".

[Jin-4] Jin QS, Kamata M, Garcia del Saz E, Seguchi H (1995). "Ultracytochemical study of trimetaphosphatase activity during acrosomal formation in the mouse testis". Histol Histopathol. 10 (3): 681–9. PMID 7579818. Unknown parameter |month= ignored (help)

[Shimizu-5] Shimizu T, Sasaki T (1991). "Ultrastructural Study of the Effects of Cytochalasin D Administration on the Structure and Acid Trimetaphosphatase Activity of Osteoclast". J Electron Microsc (Tokyo). 40 (5): 346–55. PMID 1666644. Unknown parameter |month= ignored (help)

[Mitchell-6] Mitchell PD (1961). "Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism". Nature. 191: 144–8. PMID 13771349. Unknown parameter |month= ignored (help)

[7] Irvine RF (1992). "Inositol lipids in cell signalling". Curr Opin Cell Biol. 4 (2): 212–19. PMID 1318060.

[8] Nishizuka Y (1995). "Protein kinase C and lipid signaling for sustained cellular responses". FASEB J. 9 (7): 484–96. PMID 7737456.

[Ferry-9] 9.0 ^9.1 Ferry G, Tellier E, Try A, Grés S, Naime I, Simon MF, Rodriguez M, Boucher J, Tack I, Gesta S, Chomarat P, Dieu M, Raes M, Galizzi JP, Valet P, Boutin JA, Saulnier-Blache JS (2003). "Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity". J Biol Chem. 278 (20): 18162–9. doi:10.1074/jbc.M301158200. PMID 12642576. Unknown parameter |month= ignored (help)

[Werner-10] 10.00 ^10.01 ^10.02 ^10.03 ^10.04 ^10.05 ^10.06 ^10.07 ^10.08 ^10.09 ^10.10 ^10.11 ^10.12 ^10.13 ^10.14 ^10.15 ^10.16 Werner A, Dehmelt L, Nalbant P (1998). "Na+-dependent phosphate cotransporters: the NaPi protein families". J Exp Biol. 201 (Pt 23): 3135–42. PMID 9808829. Unknown parameter |month= ignored (help)

[Ruddy-11] Ruddy DA, Kronmal GS, Lee VK, Mintier GA, Quintana L, Domingo R Jr, Meyer NC, Irrinki A, McClelland EE, Fullan A, Mapa FA, Moore T, Thomas W, Loeb DB, Harmon C, Tsuchihashi Z, Wolff RK, Schatzman RC, Feder JN (1997). "A 1.1-Mb transcript map of the hereditary hemochromatosis locus". 7 (5): 441–56. PMID 9149941. Unknown parameter |month= ignored (help)

[Ho-12] 12.0 ^12.1 ^12.2 ^12.3 ^12.4 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)

[Csapo-13] 13.0 ^13.1 ^13.2 ^13.3 ^13.4 Joseph Csapo (1927). "The Influence of Proteins on the Solubility of Calcium Phosphate". J Biol Chem. 75 (2): 509–15.

[Rutsch-14] 14.0 ^14.1 ^14.2 ^14.3 ^14.4 ^14.5 ^14.6 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)

[Murer-15] 15.00 ^15.01 ^15.02 ^15.03 ^15.04 ^15.05 ^15.06 ^15.07 ^15.08 ^15.09 ^15.10 ^15.11 ^15.12 ^15.13 ^15.14 ^15.15 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)

[Hernando-16] 16.0 ^16.1 ^16.2 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)

[Kavanaugh-17] 17.0 ^17.1 ^17.2 Kavanaugh MP, Miller DG, Zhang W, Law W, Kozak SL, Kabat D, Miller AD (1994). "Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters". Proc Natl Acad Sci U S A. 91 (15): 7071–5. PMID 8041748. Unknown parameter |month= ignored (help)

[Bottger-18] 18.0 ^18.1 ^18.2 ^18.3 ^18.4 ^18.5 ^18.6 ^18.7 Bøttger P, Hede SE, Grunnet M, Høyer B, Klaerke DA, Pedersen L (2006). "Characterization of transport mechanisms and determinants critical for Na+-dependent Pi symport of the PiT family paralogs human PiT1 and PiT2". Am J Physiol Cell Physiol. 291 (6): C1377–87. PMID 16790504. Unknown parameter |month= ignored (help)

[Marks-19] 19.0 ^19.1 ^19.2 ^19.3 Marks J, Churchill LJ, Debnam ES, Unwin RJ (2008). "Matrix extracellular phosphoglycoprotein inhibits phosphate transport". J Am Soc Nephrol. 19 (12): 2313–20. PMID 19005008. Unknown parameter |month= ignored (help)

[Lotscher-20] 20.00 ^20.01 ^20.02 ^20.03 ^20.04 ^20.05 ^20.06 ^20.07 ^20.08 ^20.09 ^20.10 ^20.11 Lötscher M, Kaissling B, Biber J, Murer H, Levi M (1997). "Role of microtubules in the rapid regulation of renal phosphate transport in response to acute alterations in dietary phosphate content". J Clin Invest. 99 (6): 1302–12. PMID 9077540. Unknown parameter |month= ignored (help)

[Roberts-21] 21.0 ^21.1 ^21.2 Roberts R, Sciorra VA, Morris AJ (1998). "Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform". J Biol Chem. 273 (34): 22059–67. PMID 9705349. Unknown parameter |month= ignored (help)

[Huang-22] 22.0 ^22.1 Huang Y, Lemieux MJ, Song J, Auer M, Wang DN (2003). "Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli". Science. 301 (5633): 616–20. PMID 12893936. Unknown parameter |month= ignored (help)

[cd06174-23] "Major Facilitator Superfamily".

[Lide-24] CRC Handbook of Chemistry and Physics (88th ed.). Boca Raton, Florida: CRC Press. 2007–2008. p. 7-18. Unknown parameter |editor-in-chief= ignored (help)CS1 maint: Date format (link)

[Schwartz-25] 25.0 ^25.1 Schwartz MK. "Phosphate metabolism". McGraw-Hill Encyclopedia of Science & Technology (9th ed.). 13: 343–4.

[Buono-26] Buono MJ, Kolkhorst FW (2001). "Estimating ATP resynthesis during a marathon run: a method to introduce metabolism" (PDF). Adv Physiol Educ. 25 (2): 70–1.

[Guigas2-27] Guigas G, Weiss M (2008). "Sampling the Cell with Anomalous Diffusion—The Discovery of Slowness". Biophys J. 94 (1): 90–4. doi:10.1529/biophysj.107.117044. PMID 17827216. Unknown parameter |month= ignored (help)

[Matsumura-28] Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y (1998). "Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein". Biochem Biophys Res Commun. 242 (3): 626–30. PMID 9464267. Unknown parameter |month= ignored (help)

[Urakawa-29] Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T (2006). "Klotho converts canonical FGF receptor into a specific receptor for FGF23". Nature. 444 (7120): 770–4. PMID 17086194. Text "month-Dec " ignored (help)

[Shimada-30] Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004). "FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis". J Bone Miner Res. 19 (3): 429–35. doi:10.1359/JBMR.0301264. PMID 15040831. Unknown parameter |month= ignored (help)

[FGF23-31] "Entrez Gene: FGF23 fibroblast growth factor 23".

[Kato-32] 32.0 ^32.1 Kato K, Jeanneau C, Tarp MA, Benet-Pagès A, Lorenz-Depiereux B, Bennett EP, Mandel U, Strom TM, Clausen H (2006). "Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation". J Biol Chem. 281 (27): 18370–7. PMID 16638743. Unknown parameter |month= ignored (help)

[Bergwitz-33] 33.0 ^33.1 ^33.2 ^33.3 Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H (2006). "SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis". Am J Hum Genet. 78 (2): 179–92. PMID 16358214. Unknown parameter |month= ignored (help)

[Liu-34] 34.0 ^34.1 Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD (2003). "Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX". J Biol Chem. 278 (39): 37419–26. doi:10.1074/jbc.M304544200. PMID 12874285. Unknown parameter |month= ignored (help)

[Toda-35] Toda K, Yabe I (2004). "Mathematical model of cell growth and phosphatase biosynthesis in Saccharomyces carlsbergensis under phosphate limitation". Biotech Bioeng. 21 (3): 487–502. doi:10.1002/bit.260210310. Unknown parameter |month= ignored (help)

[Sidossis-36] Sidossis LS, Mittendorfer B, Chinkes D, Walser E, Wolfe RR (1999). "Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism". Am J Physiol. 276 ((3 Pt 1)): E427–34. PMID 10070006. Unknown parameter |month= ignored (help)

[Lu-37] Lu W, Wang X, Zhao X (2007). "Study of vascular smooth muscle cell calcification induced by hyperphosphate and intervented by phosphonoformic acid". J Nanjing Med Univ. 21 (6): 377–81. doi:10.1016/S1007-4376(07)60082-3. Unknown parameter |month= ignored (help)

[Specktor-38] Specktor P, Cooper JG, Indelman M, Sprecher E (2006). "Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred". J Hum Genet. 51 (5): 487–90. PMID 16528452.

[Ichikawa-39] Ichikawa S, Guigonis V, Imel EA, Courouble M, Heissat S, Henley JD, Sorenson AH, Petit B, Lienhardt A, Econs MJ (2007). "Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations". J Clin Endocrinol Metab. 92 (5): 1943–7. PMID 17311862. Unknown parameter |month= ignored (help)

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@@ Line 74: / Line 74: @@
 =[[Blood]]=
-Blood is a specialized body ECF contained within the cardiovascular system that is composed of [[blood cell]]s [[Suspension (chemistry)|suspended]] in [[Blood plasma|plasma]]. Its phosphate content is in many forms. Per the [[list of human blood components]]: [[adenosine triphosphate]] (ATP) concentration in whole blood is 3.1-5.7 x 10<sup>-4</sup> g/cm<sup>3</sup>, which is the equivalent of 5-10 x 10<sup>-5</sup> g/cm<sup>3</sup> of phosphorus; diphosphoglycerate is 8-16 x 10<sup>-5</sup> g/cm<sup>3</sup>; [[cGMP]] is 0.6-4.4 x 10<sup>-9</sup> g/cm<sup>3</sup>; hexosephosphate P is 1.4-5 x 10<sup>-5</sup> g/cm<sup>3</sup> (0-2 x 10<sup>-6</sup> g/cm<sup>3</sup> in [[Blood plasma|plasma]] or [[serum]]); [[DNA]] is 0-1.6 x 10<sup>-5</sup> g/cm<sup>3</sup> in plasma or serum; [[phospholipid]] is 2.25-2.85 x 10<sup>-3</sup> g/cm<sup>3</sup> (5-12 x 10<sup>-5</sup> g/cm<sup>3</sup> in plasma or serum); pyrimidine nucleotide is 2.6-4.6 x 10<sup>-5</sup> g/cm<sup>3</sup> (2-12 x 10<sup>-7</sup> g/cm<sup>3</sup> in plasma or serum); [[RNA]] is 5-8 x 10<sup>-4</sup> g/cm<sup>3</sup> (4-6 x 10<sup>-5</sup> g/cm<sup>3</sup> in plasma or serum). P<sub>i</sub> occurs in blood, blood plasma and blood serum.<ref name=Csapo>{{ cite journal |author=Joseph Csapo |title=The Influence of Proteins on the Solubility of Calcium Phosphate |journal=J Biol Chem. |volume=75 |issue=2 |pages=509-15 |year=1927 }}</ref> The total phosphorus content is 2-3.9 x 10<sup>-5</sup> g/cm<sup>3</sup> as inorganic phosphate and 3.5-4.3 x 10<sup>-4</sup> g/cm<sup>3</sup> total (2.3-4.5 x 10<sup>-5</sup> g/cm<sup>3</sup> and 1-1.5 x 10<sup>-4</sup> g/cm<sup>3</sup> in plasma or serum, respectively).
+Blood is a specialized body ECF contained within the cardiovascular system that is composed of [[blood cell]]s [[Suspension (chemistry)|suspended]] in [[Blood plasma|plasma]]. Its phosphate content is in many forms. Per the [[list of human blood components]]: [[adenosine triphosphate]] (ATP) concentration in whole blood is 3.1-5.7 x 10<sup>-4</sup> g/cm<sup>3</sup>, which is the equivalent of 5-10 x 10<sup>-5</sup> g/cm<sup>3</sup> of phosphorus; diphosphoglycerate is 8-16 x 10<sup>-5</sup> g/cm<sup>3</sup>; [[cGMP]] is 0.6-4.4 x 10<sup>-9</sup> g/cm<sup>3</sup>; hexosephosphate P is 1.4-5 x 10<sup>-5</sup> g/cm<sup>3</sup> (0-2 x 10<sup>-6</sup> g/cm<sup>3</sup> in [[Blood plasma|plasma]] or [[serum]]); [[DNA]] is 0-1.6 x 10<sup>-5</sup> g/cm<sup>3</sup> in plasma or serum; [[phospholipid]] is 2.25-2.85 x 10<sup>-3</sup> g/cm<sup>3</sup> (5-12 x 10<sup>-5</sup> g/cm<sup>3</sup> in plasma or serum); pyrimidine nucleotide is 2.6-4.6 x 10<sup>-5</sup> g/cm<sup>3</sup> (2-12 x 10<sup>-7</sup> g/cm<sup>3</sup> in plasma or serum); and [[RNA]] is 5-8 x 10<sup>-4</sup> g/cm<sup>3</sup> (4-6 x 10<sup>-5</sup> g/cm<sup>3</sup> in plasma or serum). P<sub>i</sub> occurs in blood, blood plasma and blood serum.<ref name=Csapo>{{ cite journal |author=Joseph Csapo |title=The Influence of Proteins on the Solubility of Calcium Phosphate |journal=J Biol Chem. |volume=75 |issue=2 |pages=509-15 |year=1927 }}</ref> The total phosphorus content is 2-3.9 x 10<sup>-5</sup> g/cm<sup>3</sup> as inorganic phosphate and 3.5-4.3 x 10<sup>-4</sup> g/cm<sup>3</sup> total (2.3-4.5 x 10<sup>-5</sup> g/cm<sup>3</sup> and 1-1.5 x 10<sup>-4</sup> g/cm<sup>3</sup> in plasma or serum, respectively).
 ==Blood Orthophosphate==

Phosphate homeostasis: Difference between revisions