Calcium, chelation release

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

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... 

Removal of calcium ions makes unfolding of a-lactalbumin irreversible. The denaturation temperature of a-lactalbumin decreased 20 °C when calcium ions were removed by a chelator (Bemal and Jelen 1984). Hillier et al (1979) found that an increase in the calcium concentration up to 0.4 mg/ml slowed the heat denaturation of a-lactalbumin, but additional calcium had little effect. There is a slow conformational change at pH 4 as calcium is released from carboxyl groups on the protein surface (Kronman et al 1964). Failure to measure the heat of denaturation for a-lactalbumin at pH 3 shows the protein chain is already unfolded at low pH (de Wit and Klarenbeek 1984). 

Calcium chelate compound that releases free calcium ion within cells upon irradiation with ultraviolet light.Pl... 

Based on this observation, calcium released from this complex requires high-temperature heating in combination with a calcium chelating and/or precipitating agent such as EDTA, EGTA, citrate buffer, or urea. Because these reagents are chelators of divalent... 

Ca2+ levels, with one of the intracellular calcium-chelating, fluorescent probes, quin-2, fura-2 or indo-1, demonstrates that, in both cases, there is a rapid rise in intracellular Ca2+ as this ion is released from intracellular stores. Analysis of stimulated B lymphocytes, using the probe fura-2, indicates that if Ca2+ in the external medium is removed the intracellular Ca2+ level returns to basal levels in 5 to 7 minutes, but if there is Ca2+ present in the external media a sustained increase in intracellular Ca2+ is detected [36]. Such analysis suggests the opening of a plasma membrane calcium channel but the nature of the channel or mechanism of its opening are not presently known. It is possible that the opening of this channel could be stimulated by one of the inositol phosphates. 

Actions. These compounds are effective calcium chelators that rapidly target exposed bone mineral surfaces in vivo, where they can be released by bone-resorbing osteoclasts, resulting in inhibition of osteoclast function and osteoclast apoptosis. The bisphosphonates (alendronate, clodronate, etidronate, pamidronate, risedronate, tiludronate and zoledronate) inhibit the activation and function of osteoclasts and possibly directly stimulate formation of bone by the osteoblasts. They also bind strongly to hydroxyapatite crystals and, in high doses, can inhibit the mineralisation of bone. The doses at which effects on mineralisation occur are not related to antiresorptive efficacy. There is wide variation between these compoimds in terms of their capacity to inhibit... 

The tetracyclines produce a small effect, partly by calcium chelation, thus reducing transmitter release. Reversal is usually, but inconsistently, obtained with calcium or neostigmine. 

Edetic acid and edetate salts are used in pharmaceutical formulations, cosmetics, and foods as chelating agents. They form stable water-soluble complexes (chelates) with alkaline earth and heavy metal ions. The chelated form has few of the properties of the free ion, and for this reason chelating agents are often described as removing ions from solution this process is also called sequestering. The stability of the metal-edetate complex depends on the metal ion involved and also on the pH. The calcium chelate is relatively weak and will preferentially chelate heavy metals, such as iron, copper, and lead, with the release of calcium ions. For this reason, edetate calcium disodium is used therapeutically in cases of lead poisoning see also Section 18. 

Figure 15.4 Examples of caged compounds and other photoactivatable drugs, (a) and (b) on photolysis the o-nitrobenzyl protecting group detaches and releases ATP and cAMP, respectively (c) photosensitive chelator. The cis form of the molecule binds Zn2+ but the trans form does not (d) frequently used photosensitive calcium chelators. Nitr-2 (R = CH3), Nitr-5 (R = H) (e) ICYP-diazirine, a photoaffinity reagent that becomes covalently attached to p-adrenergic receptors upon photolysis.

Selected entries from Methods in Enzymology [vol, page(s)] Chelation, 238, 74, 76, 297 buffers [for analysis of exocytosis, 221, 132 preparation, 219, 186 modulation of cytosolic buffering capacity with quin2, 221, 159] fluorescence assay, 240, 724-725, 740-742 fluorescence imaging, 225, 531 238, 303-304, 322-325, 334-335 free intracellular levels after bacterial invasion, 236, 482-489 free calcium in solutions for membrane fusion analysis, calculation and control, 221, 149 homeostasis mechanisms, 238, 80 hormonal elevation, 238, 79 inositol phosphate effect on release, 238, 207 determination of cytosolic levels [computer methods, 238, 73-75 with fura-2, 238, 73, 146 with indo-1, 238, 298, 316-317 with quin-2, 238, 297] hormone effects, 238, 79 ionomycin effects, 238, 79 membrane depolarization effects,... 

A calcium ion indicator dye (based on the structure of the chelator EGTA) that exhibits a strong fluorescence at 385 nm and can be used to measure changes in intracellular Ca concentration. The approximate dissociation constant for the Ca -Fura-2 complex is 0.1 juM, depending on cellular ion composition and pH. An esteri-fied derivative of Fura-2 readily crosses the peripheral membrane of many cells and, after hydrolysis, the release of Fura-2 permits calcium ion measurements within cells. See Calcium Ion Indicator Dyes Metal Ion Complex-ation... 

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