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Titolo:
Refinement and evaluation of a model of Mg2+ buffering in human red cells
Autore:
Raftos, JE; Lew, VL; Flatman, PW;
Indirizzi:
Monash Univ, Dept Physiol, Clayton, Vic 3168, Australia Monash Univ Clayton Vic Australia 3168 siol, Clayton, Vic 3168, Australia Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England Univ Cambridge Cambridge England CB2 3EG Lab, Cambridge CB2 3EG, England Univ Edinburgh, Sch Med, Dept Biomed Sci, Membrane Biol Grp, Edinburgh, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland burgh, Midlothian, Scotland
Titolo Testata:
EUROPEAN JOURNAL OF BIOCHEMISTRY
fascicolo: 3, volume: 263, anno: 1999,
pagine: 635 - 645
SICI:
0014-2956(199908)263:3<635:RAEOAM>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTRACELLULAR FREE MAGNESIUM; NUCLEAR-MAGNETIC-RESONANCE; ADENOSINE 5'-TRIPHOSPHATE; HUMAN HEMOGLOBIN; BLOOD-CELLS; ERYTHROCYTE-MEMBRANES; CALCIUM EXTRUSION; IONIZED MAGNESIUM; ATP DEPENDENCE; ION;
Keywords:
computer simulation; erythrocyte; hemoglobin; human; magnesium ions;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Raftos, JE Monash Univ, Dept Physiol, Clayton, Vic 3168, Australia Monash Univ Clayton Vic Australia 3168 on, Vic 3168, Australia
Citazione:
J.E. Raftos et al., "Refinement and evaluation of a model of Mg2+ buffering in human red cells", EUR J BIOCH, 263(3), 1999, pp. 635-645

Abstract

The total Mg2+ content of human red cells ([Mg](T,i)) is partitioned between free and bound forms. The main cytoplasmic Mg2+ buffers are ATP and 2,3 bisphosphoglycerate. Haemoglobin binds free ATP and bisphosphoglycerate, preferentially in the deoxygenated state. Thus, the free ionized Mg2+ concentration ([Mg2+](i)) oscillates with the oxy-deoxy condition of the cells. The binding reactions are also modulated by the pH changes that accompany theoxygenation-deoxygenation transitions. The complex interactions between Mg2+, its ligands and Hb can be encoded in a set of equilibrium equations representing all the known binding reactions of the system. To develop a comprehensive understanding of the Mg2+ homeostasis of intact red cells it is necessary to correct and refine the equations and parameters of the model by systematic comparisons between model predictions and measured cytoplasmic Mg2+ buffering curves under a variety of experimental conditions. Earlier models largely underestimated total Mg2+ binding in intact cells. We carried out experiments in which [Mg](T,i) and [Mg2+](i) were controlled over a wide range ([Mg](T,i) between 0.1 and 23 mM) by the use of the ionophore A23187, under diverse metabolic conditions, and the results were used to interpret the adjustments required for good model fits. By the inclusion of low-affinity Mg2+ binding to ATP and bisphosphoglycerate, and also binding of Mg2 to haemoglobin (four ions per tetramer) with an apparent dissociation constant of 45 mM we were able to realistically model, for the first time, allthe experimentally observed changes in [Mg2+](i) in human red cells under diverse metabolic conditions.

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Documento generato il 01/06/20 alle ore 02:33:03