Calcium chelators

In the treatment of poisoning by lead or other metal ions, higher concentrations of chelant can be safely obtained in humans by administering Na2CaEDTA rather than Na EDTA. The metal ion is bound by displacing small amounts of Ca " that the body can tolerate. Use of Na EDTA would result in calcium chelation and thus serious depletion of calcium in the body fluids (44). Removal of iron in Cooley s anemia is accompHshed by using chelants that are relatively specific for iron (45). 

Calcium Chelates (Salicylates). Several successhil dental cements which use the formation of a calcium chelate system (96) were developed based on the reaction of calcium hydroxide [1305-62-0] and various phenohc esters of sahcyhc acid [69-72-7]. The calcium sahcylate [824-35-1] system offers certain advantages over the more widely used zinc oxide—eugenol system. These products are completely bland, antibacterial (97), facihtate the formation of reparative dentin, and do not retard the free-radical polymerization reaction of acryhc monomer systems. The principal deficiencies of this type of cement are its relatively high solubihty, relatively low strength, and low modulus. Less soluble and higher strength calcium-based cements based on dimer and trimer acid have been reported (82). 

The formulation of calcium chelate materials is based upon the formation of a low-solubiUty chelate between calcium hydroxide and a sahcylate. Dycal utilizes the reaction product of a polyhydric compound and sahcyhc acid. Other sahcyhc acid esters can be similarly used. Vehicles used to carry the calcium hydroxide, extenders, and fillers may include mineral oil, A/-ethyl- -toluenesulfonamide [80-39-7] and polymeric fluids. The filler additions may include titanium dioxide [13463-67-7] zinc oxide, sihca [7631-86-9], calcium sulfate, and barium sulfate [7727-43-7]. Zinc oxide and barium sulfate are useflil as x-ray opacifying agents to ensure a density greater than that of normal tooth stmcture. Resins, rosin, limed rosins, and modified rosins may serve as modifiers of the physical characteristics in both the unset and set states. 

The calcium chelate cements are limited to the use of a cavity liner. They may be placed directly over an exposed tooth pulp to protect the pulp and stimulate the growth of secondary dentin, or used as a therapeutic insulating base under permanent restorations. The high alkalinity and high solubihty of these materials prohibits use in close proximity to soft tissues or in contact with oral fluids. 

Fig. 4.1.8 Influence of various calcium chelators on the relationship between Ca2 " concentration and the luminescence intensity of aequorin, at 23-25°C (panel A) in low-ionic strength buffers (I < 0.005) and (panel B) with 150 mM KC1 added. Buffer solutions (3 ml) of various Ca2+ concentrations, pH 7.05, made with or without a calcium buffer was added to 2 pi of 10 pM aequorin solution containing 10 pM EDTA. The calcium buffer was composed of the free form of a chelator (1 or 2mM) and various concentrations of the Ca2+-chelator (1 1) complex to set the Ca2+ concentrations (the concentration of free chelator was constant at all Ca2+ concentrations). The curves shown are obtained with 1 mM MOPS (A), 1 mM gly-cylglycine ( + ), 1 mM citrate (o), 1 mM EDTA plus 2mM MOPS ( ), 1 mM EGTA plus 2 mM MOPS ( ), 2 mM NTA plus 2 mM MOPS (V), and 2 mM ADA plus 2 mM MOPS (A). In the chelator-free buffers, MOPS and glycylglycine, Ca2+ concentrations were set by the concentration of calcium acetate. Reproduced with permission, from Shimomura and Shimomura, 1984. the Biochemical Society.

Microtubules can be reconstituted in vitro at 37 °C from a solution that contains a physiological mixture of brain tubulin, MAPs, small amounts of guanosine 5 -triphosphate (GTP), magnesium ions, and the calcium-chelating agent EGTA [ethylene glycol-bis(2-aminoethyl ether) N, N -tetraacetic acid]. Tubulin assembly is inhibited by low temperature and by the presence of calcium ions. 

Cantoni, O., Sestili, P., Cattabeni, F., Bellomo, G., Pou, S., Cohen, M. and Cerutti, P. (1989). Calcium chelator quin 2 prevents hydrogen-peroxide-induced DNA breakage and cytotoxicity. Eur. J. Biochem. 181, 209-212. 

The interest in colour indicators has recently increased as they are used for the direct determination of pH (acid-base indicators) and free calcium ions (fluorescent derivatives based on the calcium chelator EGTA as metallochromic indicators) in biological systems at cellular level. 

If the ratio of the calcium chelate salt to the trihydrated barium salt in a mixture is above 2 1, the thermal decomposition during DTA/TG analysis may be explosive. See other metal perchlorates... 

Morgan JM, Navabi H, Jasani B. Role of calcium chelation in high-temperature antigen retrieval at different pH values. J. Pathol. 1997 182 233-237. 

EDTA salts are used for the treatment of heavy metal poisoning. Roosels and Vanderkeel142) were able to extract lead from urine in the presence of EDTA with dithizone by adding calcium to presumably release the lead from EDTA. In view of the fact that the formation constant of the lead-EDTA chelate is 20,000,000 times larger than that of the corresponding calcium chelate, it is doubtful that the calcium actually releases the EDTA from the lead. 

Adler EM, Augustine GJ, Duffy SN, Charlton MP 1991 Alien intracellular calcium chelators attenuate neurotransmiter release at the squid giant synapse. J Neurosci 11 1496-1507 Bayguinov O, Hagen B, Sanders KM 2001 Muscarinic stimulation increases basal Ca2+ and inhibits spontaneous Ca2+ transients in murine colonic myocytes. Am J Physiol 280 C689-C700... 

In calcium chelators Indo-1 (17) and Fura-3 (18b) (Figure 2.9),(18) the fluoropho-res have donor-acceptor stilbene-like structures rigidified so as to avoid photoisomerization. Based on the same principle, Fura-2 (18a)a8) is one of the most popular calcium indicator for microscopy of individual cells because, in contrast to Quin-2 (see Section 2.2.5.), the excitation spectrum is blue shifted on cation binding, thus allowing intensity-ratio measurements. On the other hand, there is almost no shift of the emission spectrum, which can be interpreted along the same line as DCM-crown (see earlier in this section). 

Most of the fluorescent calcium indicators and their cell-permeant acetoxymethyl (AM) esters are variations of the nonfluorescent calcium chelator BAPTA and have been proposed by Tsien/134-1365 Among them Fura-2 and Indo-1 (Figure 5.22) are particularly used formeasuring Ca2+in single cells by imaging or flow cytometry/65... 

K. M. Hirshfeld, D. Toptygin, B. S. Packard, andL. Brand, Dynamic fluorescence measurements of two-state systems Applications to calcium chelating probes, Anal. Biochem. 209, 209-218 (1993). 

A UV laser is needed for exciting the blue-fluorescing agents, 4, 6-diamidino-2-phenyhndole (DAPI) and Hoechst 33342, which are DNA-intercalating stains, and for indo-1, a fluorescent calcium chelator dye. Violet diode lasers that are offered in some newer instruments accommodate fluorochromes such as Cascade Blue, Pacific Blue, and cyan fluorescent protein, and are also capable of exciting DAPI (Shapiro and Perlmutter 2001 Telford et al., 2003). 

Peter-Witt E, Wolf V. 1985. Comparison of diethylenetriaminepentaacetic acid calcium chelate and diethylenetriaminepentaacetic acid zinc chelate in removing thorium-234 from the rat. Health Phys 49 395-404. 

It is also important to note that the coagulation mechanism in vivo does not occur in solution, but is localized to activated cell surfaces expressing anionic phospholipids such as phosphatidylserine, and is mediated by Ca2+ bridging between the anionic phospholipids and 7-carboxyglutamic acid residues of the clotting factors. This is the basis for using calcium chelators such as ethylenediamine tetraacetic acid (EDTA) or citrate to prevent blood from clotting in a test tube. 

Carboxylates are weaker cheiants and are mainly used for calcium chelation, for example, in cleaning and food applications. These include gluconates, glucohepto-nates, and citrates (Figure 10.4). 

In the absence of a calcium gradient the energy required for the incorporation of phosphate must be provided by the removal of calcium from the protein alone. Since the protein and the calcium chelator EGTA have approximately the same affinity for calcium, the driving force for phosphate binding originates from the reduction of the concentration of ionized calcium alone. 

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