Calcium citrate, Inhibited

PHEMA into an SBF solution. At the higher released citric acid concentrations, the formation of calcium citrate crystals can bring about a depletion of the calcium ion concentration in the SBF solution, so less calcium phosphate will precipitate onto the polymer. At lower citric acid concentrations, the inhibition effect of citrate anions on formation of calcium phosphates has been attributed to the complex equilibria between calcium, citrate and phosphate ions (27-29). Precipitated calcium phosphates may undergo dissolution via surface exchange between phosphate and citrate ions (calcium citrate is much more soluble than calcium phosphate). 

Antinozzi ef al. [19] studied the inhibition of calcium oxalate in the presence of citrate ions. It is worth emphasizing that these authors were very careful to ensure that the addition of citrate ions in the form of calcium citrate did not influence the concentration of the calcium ions in the solution. In taking this approach, they could ensure that the observed effects can be correlated with the citrate concentrations alone and avoid any additional common ion effects. 

Antinozzi, P.A., Brown, C.M., and Purich, D.L. (1992) Calcium oxalate monohydrate crystallization citrate inhibition of nucleation and growth steps. J. Cryst. Growth, 125, 215-222. 

It is far from clear whether the incorporation of the citrate ion into calcified tissues is merely a consequence of the stability and solubility properties of calcium citrates or whether it plays an essential part in the mineralization process. It increases the solubility of apatite and inhibits alkaline phosphatase. Citrate accumulation in bone is influenced by both parathormone and vitamin D. High levels of vitamin D appear to stimulate osteocytes to produce citrate and this may play some part in the subsequent increase in resorption. Despite these observations no clear picture of the role of citrate in mineralization has emerged. 

Calcium is essential to several steps in the enzyme cascade of the blood clotting process, such as the conversion of prothrombin to thrombin (23). Clotting can be inhibited in stored blood suppHes by addition of complexing agents such as EDTA or citrate which reduce the levels of the free ion, Ca(Il). 

The most direct evidence for surface precursor complex formation prior to electron transfer comes from a study of photoreduc-tive dissolution of iron oxide particles by citrate (37). Citrate adsorbs to iron oxide surface sites under dark conditions, but reduces surface sites at an appreciable rate only under illumination. Thus, citrate surface coverage can be measured in the dark, then correlated with rates of reductive dissolution under illumination. Results show that initial dissolution rates are directly related to the amount of surface bound citrate (37). Adsorption of calcium and phosphate has been found to inhibit reductive dissolution of manganese oxide by hydroquinone (33). The most likely explanation is that adsorbed calcium or phosphate molecules block inner-sphere complex formation between metal oxide surface sites and hydroquinone. 

Resorption of the required mineral substances from food usually depends on the body s requirements, and in several cases also on the composition of the diet. One example of dietary influence is calcium (see p. 342). Its resorption as Ca is promoted by lactate and citrate, but phosphate, oxalic acid, and phytol inhibit calcium uptake from food due to complex formation and the production of insoluble salts. 

The mechanism of action for aluminum toxicity is not known, but the element is known to compete in biological systems with cations, especially magnesium (MacDonald and Martin 1988) despite an oxidation state difference, and to bind to transferrin and citrate in the blood stream (Gannot 1986). It may also affect second messenger systems and calcium availability (Birchall and Chappell 1988), and irreversibly bind to cell nucleus components (Crapper-McLachlan 1989 Dryssen et al. 1987). Aluminum has also been shown to inhibit neuronal microtubule formation. However, much more work is needed before a mechanism can be proposed. 

CAIs alter renal function primarily by inhibiting carbonic anhydrase in the proximal tubule, which results in decreased bicarbonate reabsorption. The net effect of the renal actions of acetazolamide therapy is alkaliniza-tion of the urine and metabolic acidosis. Metabolic acidosis results from the initial bicarbonate loss and persists with continued acetazolamide use. Moderate metabolic acidosis develops in most patients. Reabsorption of bicarbonate independent of carbonic anhydrase prevents severe acidosis. Initially, acetazolamide produces diuresis, but urinary output decreases with the development of metabolic acidosis. In addition, decreased urinary citrate excretion follows acetazolamide therapy and has been attributed to the metabolic acidosis it produces. A high urinary pH and low urinary citrate concentration are conducive to precipitation of calcium phosphate in both the renal papillae and the urinary tract. 

Calcareous stones result from hypercalciuria, hyperoxaluria and hypocitraturia. Hypercalciuria and hyperoxaluria render urine supersaturated in respect of calcium salts citrate makes calcium oxalate more soluble and inhibits its precipitation from solution. 

Smail crystals of calcium oxalate are a normal component of the urine. They form in the glomerular filtrate as water is reabsorbed and the urine is concentrated, Theurineofmostpersonscontainscompoundsthat inhibit the grow th of c rysta Is. These inhibitors include magnesium, citrate, pyrophosphate, and mucopolysaccharides. Apparently, persons who tend to form renal and bladder stones have reduced levels of these Inhibitors. Slone formation has a genetic component. The disease may "run in the family."... 

By inhibiting carbonic anhydrase, topiramate reduces the urinary excretion of citrate and increases urinary pH, leading to higher calcium phosphate saturation and a risk of nephrolithiasis. During 1074 patient-years of topiramate exposure in 1183 patients, 18 (1.5%) had 21 episodes of renal calcuh, suggesting an incidence of nephrohthiasis comparable to that reported for acetazol-amide (SEDA-20, 66). 

Sodium citrate solution, at a concentration of 34 to 38 g/L in a ratio of 1 part to 9 parts of blood, is widely used for coagulation studies because the effect is easily reversible by addition of Ca. Because citrate chelates calcium, it is unsuitable as an anticoagulant for specimens for measurement of this element. It also inhibits aminotransferases and alkaline phosphatase but stimulates acid phosphatase when phenylphosphate is used as a substrate. Because citrate complexes molybdate, it decreases the color yield in phosphate measurements that involve molybdate ions and produces low results. 

Binding of iron by dietary fiber is strongly inhibited by ascorbic acid, citrate, cysteine, EDTA or phytate in concentrations as lew as 100 >uMols/Liter (A3). The inhibitors have the common property of being able to form soluble complexes with iron. The decarbox-ylic amino acids and their amides inhibit binding moderately as do lysine and histidine. Other amino acids either do not interfere with binding of iron fiber or do so only weakly. Calcium (as acetate) and phosphate act as moderate inhibitors. The detergents sodium lauryl sulfonate or cetyltrimethylammonium bromide had no effect on iron binding by fiber (A2). 

Dissolved calcium and phosphate ions may remain soluble despite their concentrations exceeding the solubility product in blood plasma and stromal extracellular (interstitial) fluid where the pH is just above 7 (Sect. 3.3.1). In blood plasma, mineralization is prevented by polyanions, especially albumin, citrate, and pyrophosphate (PPi), which chelate calcium ions and prevent their precipitation with monohydrogen phosphate ions (orthophosphate, Pi, or HP042-). Pyrophosphate (PPi) inhibits the premature aggregation of calcium with monohydrogen phosphate ions in mineralizing tissues and interstitial fluid throughout the body (Fig. 9.1b). 

Osteoblasts secrete osteoid, a matrix rich in type I collagen fibers and vesicles. Precipitation of calcium phosphate is inhibited by a high concentration of pyrophosphate in stromal interstitial fluids, and a high concentration also of albumin and citrate in blood plasma. Pyrophosphate is derived from (1) transport out of the cytosol, and (2) synthesis from nucleoside triphosphates in the stromal interstitial fluid that permeates the osteoid matrix. Precipitation occurs only when calcium and phosphate ions are taken up into vesicles whose inner membrane is composed of phosphatidylserine. The high concentration of calcium and phosphate ions in the vesicle is mediated by annexin and type HI Pi Na-dependent transporters. This overwhelms the pyrophosphate and nucleation occurs. As the precipitate grows and ruptures the membrane, tissue-nonspecific alkaline phosphatase is activated to remove pyrophosphate from the osteoid matrix fluid so that calcium phosphate precipitates around phosphorylated serine residues within the collagen fibers. 

Sodium xylenesulfonate, sodium cumenesulfonate Sodium citrate, sodium tripolyphosphate Enzymes (stain remover), borax (cleaning aid), sodium formate, calcium chloride (enzyme stabilizing system), hydrogen peroxide (bleach), soil release polymers (soil release), polyvinylpyrrolidone (dye transfer inhibition)... 

Other reports (27-29) have focused on the role of citric acid, as a source of carboxylate anions, during precipitation of calcium phosphates from electrolyte solutions. It has been found that citrate anions inhibit the ciystal growth of calcium phosphates and hinder their transformation into hydroxyapatites. This was attributed to the adsorption of citrate anions into the crystals and the displacement of an equivalent amount of phosphate anions. Interestingly, Rhee and Tanaka (30) found that the presence of a collagen membrane in the medium changed the behavior of citrate anions from being an inhibitor to becoming a promoter of calcification, provided that the molar ratios of calcium to citric acid were between 2 and 12. 

The effect of vitamin D deficiency upon plasma calcium is not primarily due to malabsorption of calcium from the gastrointestinal tract. In addition to its well-known effect on calcium absorption, vitamin D contributes directly to the maintenance of plasma calcium by the skeleton by a direct action on bone similar to that of parathyroid hormone (C2, C16). The vitamin D effect may be mediated by an action on the Krebs glycolytic cycle, resulting in inhibition of citrate oxidation (S6). 

The results of dietary zinc analysis need to be considered in terms of the availability of the zinc in the food for intestinal absorption. The zinc content of whole meals and the total daily zinc intake are not sufficient information on their own, without knowledge of factors which inhibit or promote intestinal absorption (O Dell, 1984). Free ionic zinc probably does not exist in the intestinal tract, zinc being bound to molecular species such as protein, amino acids, phytic acid, citrate and others. The bioavailability of the metal is determined by the nature of these zinc binding ligands. When the zinc complex is insolubie as in Zn-phytate, the uptake from diet is poor, whereas zinc-protein or zinc-amino acid complexes are more easily dissociated and are a good source of available zinc. Other dietary components affect zinc absorption such as the amount of iron, calcium and phosphate. 

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