Calcium phosphate inhibition

Evaluation of the Copolymers The polymer solutions were evaluated for their deposit control and dispersant activities. The tests included calcium phosphate inhibition, calcium carbonate inhibition, iron oxide dispersion, and clay dispersion. The procedures for these tests have been previously reported (12). A commercially available polyacrylic acid was also tested for comparison. The results are shown in Tables II to V. 

The most commonly used scale inhibitors are low molecular weight acrylate polymers and organophosphoms compounds (phosphonates). Both classes of materials function as threshold inhibitors however, the polymeric materials are more effective dispersants. Selection of a scale control agent depends on the precipitating species and its degree of supersaturation. The most effective scale control programs use both a precipitation inhibitor and a dispersant. In some cases this can be achieved with a single component (eg, polymers used to inhibit calcium phosphate at near neutral pH). 

Sodium carboxymethyl chitin and phosphoryl chitin had most evident influences on the crystallization of calcium phosphate from supersaturated solutions. They potently inhibited the growth of hydroxyapatite and retarded the rate of spontaneous calcium phosphate precipitation. These chitin derivatives were incorporated into the precipitate and influenced both the phase and morphology of the calcium phosphate formed (flaky precipitate resembling octacalcium phosphate instead of spherical clusters in the absence of polysaccharide) [175]. 

Solubilities and stabilities of calcium phosphates in natural waters have been described (735), as have the nucleation and growth of calcium phosphate from solution (736). Several species have long been known to inhibit the precipitation of calcium phosphates, for example carbohydrates (646) and statherin, the tyrosine-rich peptide which occurs in saliva (737). The role of... 

Calcium phosphate precipitation may also be involved in the fixation of phosphate fertilizer in soils. Studies of the uptake of phosphate on calcium carbonate surfaces at low phosphate concentrations typical of those in soils, reveal that the threshold concentration for the precipitation of the calcium phosphate phases from solution is considerably increased in the pH range 8.5 -9.0 (3). It was concluded that the presence of carbonate ion from the calcite inhibits the nucleation of calcium phosphate phases under these conditions. A recent study of the seeded crystal growth of calcite from metastable supersaturated solutions of calcium carbonate, has shown that the presence of orthophosphate ion at a concentration as low as 10-6 mol L" and a pH of 8.5 has a remarkable inhibiting influence on the rate of crystallization (4). A seeded growth study of the influence of carbonate on hydroxyapatite crystallization has also shown an appreciable inhibiting influence of carbonate ion.(5). 

The percent inhibition was calculated according to the equation in Table II. As shown in Table II, the results indicated that when compared to the polyacrylic acid, copolymers of acrylic acid and N-(hydroxyalkyl)-acrylamide were quite effective in inhibiting calcium phosphate formation at the normal use dosage of 10 to 20 ppm. Among the three copolymers tested, acrylic acid/... 

Parathyroid hormone is a single-chain polypeptide of 84 amino acids which is produced in the parathyroid glands. It increases serum calcium and decreases serum phosphate. In bone it promotes resorption of calcium. It indirectly increases osteoclastic activity by promoting the action of osteoblasts. It has been shown that in low doses PTH may even increase bone formation without stimulating bone resorption. In the kidney PTH increases resorption of calcium and it increases excretion of phosphate. An other important activity in the kidney is the enhanced synthesis of 1,25-dihydroxyvitamin D. An increased serum calcium level inhibits PTH secretion and increased serum phosphate decreases free serum calcium and thus stimulates PTH secretion. 

Mechanism of Action Inhibits formation, growth, and dissolution of hydroxyapatite crystals and their amorphous precursors by chemisorption to calcium phosphate surfaces ... 

Cuervo, L. A., Pita, J. C., Howell, D. S. Inhibition of calcium phosphate mineral growth by proteoglycan aggregate fractions in a synthetic lymph. Calc. Tiss. Res. 13, 1 (1973)... 

The cytosolic concentration of free Ca2+ is generally at or below 100 mi, far lower than that in the surrounding medium, whether pond water or blood plasma. The ubiquitous occurrence of inorganic phosphates (Pj and I l ,) at millimolar concentrations in the cytosol necessitates a low cytosolic Ca2+ concentration, because inorganic phosphate combines with calcium to form relatively insoluble calcium phosphates. Calcium ions are pumped out of the cytosol by a P-type ATPase, the plasma membrane Ca2+ pump. Another P-type Ca2+ pump in the endoplasmic reticulum moves Ca2+ into the ER lumen, a compartment separate from the cytosol. In myocytes, Ca2+ is normally sequestered in a specialized form of endoplasmic reticulum called the sarcoplasmic reticulum. The sarcoplasmic and endoplasmic reticulum calcium (SERCA) pumps are closely related in structure and mechanism, and both are inhibited by the tumor-promoting agent thapsigargin, which does not affect the plasma membrane Ca2+ pump. 

For example, normal urine is supersaturated with calcium oxalate. To prevent formation of renal calculi (stones)719 an inhibitory glycoprotein is present and slows the formation and growth of crystals.720 Under some disease conditions calcium carbonate stones may form in pancreatic ducts. A17 kDa lectinlike glycoprotein called lithostatine has been proposed to inhibit stone formation by binding to certain planes on CaC03 microcrystals just as antifreeze proteins (Box 4-D) inhibit ice formation.721 However, this proposed function for lithostatine is doubtful.722 723 Pathological deposits of crystalline calcium pyrophosphate and basic calcium phosphates are sometimes present in joints,724 even in Neanderthal skeletons.725... 

ANTTCAKING AGENTS. Some products, particularly food products that contain one or more hygroscopic substanoes, require the addition of an anticaking agent to inhibit formation of aggregates and lumps and thus retain tile free-flowing characteristic of the products Calcium phosphate, for example, is commonly used in instant breakfast drinks and lemonade and other soft-dnnk mixes. 

The presence of phosphate increases the ability of the mitochondria to accumulate Ca2+, partly because of the buffering effect of the phosphate on the pH of the matrix, and partly because of the precipitation of insoluble calcium phosphate within the matrix. The formation of insoluble calcium phosphate lowers the internal free [Ca2+] and favours further influx. The amorphous nature of the precipitate is of interest as the formation of crystalline hydroxyapatite would be expected. Mitochondria must contain a factor that inhibits this process. 

The precipitation of calcium phosphate in the development of bone structure is a major topic beyond the scope of this discussion. It should be noted, however, that this process can be controlled by proteins and/or polysaccharides that provide sites for nucleation and that match features in the geometry of the crystal, such as repeat distances between certain groups. Other proteins can inhibit crystal development. Granular deposits of calcium involve small crystals so that deposition and reabsorption will be rapid. The size of the crystals can be controlled by their protein and/or polysaccharide environment, or even by a vesicular membrane which could act as a template. 

Osteocalcin has two high affinity and two or three low affinity sites for calcium. It limits growth of calcium phosphate crystals, and inhibits precipitation of hydroxyapatite. This cannot be achieved by the decarboxylated protein. Calcified tissue from various sources also contains gla proteins.459 Gla proteins are not found in invertebrates. 

Various smaller molecules and ions can also inhibit the growth of crystals of calcium phosphate such as phosphocitrate, proteoglycans and trimetaphosphate. Other compounds act as accelerators. 

In general, SS/MA and the other calcium phosphate inhibitors are not as good at inhibiting calcium carbonate scale as PMA or HEDP or as good at inhibiting calcium sulfate scale as PMA and 2000 MW PAA. 

FIG. 15 Effect of lycopene on resorption of the calcium phosphate substrate coating of osteologic multitest slides in the presence of osteoclasts (Rao et al., 2003). (Lycopene I -Effect on osteoclasts Lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in ray bone marrow cultures. Reprint from Journal of Medicinal Food. 2003 6, pp. 69-78 by permission of Mary Ann Liebert, Inc., Publishers.)... 

The regulatory role of calcium ions in intermediary metabolism is well documented. Calcium has been shown to be involved in activation or inhibition of specific enzyme systems [105], For example, it activates cyclic nucleotide phosphodiesterase, phosphofructokinase, fructose 1 6 biphosphatase, glycerol phosphate dehydrogenase, pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase. Calcium ions inhibit pyruvate kinase, pyruvate carboxylase, Na+/K+-AT-Pase and adenylate cyclase. 

Francis MD, Russell RGG, Fleisch H. Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science, 1969, 165, 1264-1266. 

Extensive seeded calclte growth experiments in the presence of phosphate ion indicate that the phosphate ion adsorbs onto the crystal surface as a monolayer. At a concentration of 10" M, phosphate ion can strongly inhibit calcite formation however, short term experiments show that this monolayer adsorption removes insignificant amounts of phosphorus from solution. In experiments lasting several days a further decrease in solution phosphate concentration occurs, presumably caused by nucleation of a surface calcium phosphate phase on the calcite seed. 

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