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Titolo:
Familial phosphofructokinase deficiency is associated with a disturbed calcium homeostasis in erythrocytes
Autore:
Ronquist, G; Rudolphi, O; Engstrom, I; Waldenstrom, A;
Indirizzi:
Univ Uppsala Hosp, Dept Clin Chem, S-75185 Uppsala, Sweden Univ Uppsala Hosp Uppsala Sweden S-75185 n Chem, S-75185 Uppsala, Sweden Norrlands Univ Hosp, Dept Clin Chem, S-90185 Umea, Sweden Norrlands Univ Hosp Umea Sweden S-90185 Clin Chem, S-90185 Umea, Sweden Norrlands Univ Hosp, Dept Internal Med, S-90185 Umea, Sweden Norrlands Univ Hosp Umea Sweden S-90185 ternal Med, S-90185 Umea, Sweden
Titolo Testata:
JOURNAL OF INTERNAL MEDICINE
fascicolo: 1, volume: 249, anno: 2001,
pagine: 85 - 95
SICI:
0954-6820(200101)249:1<85:FPDIAW>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATPASE ACTIVITY; ENZYME COMPLEX; MUSCLE; DEFORMABILITY; INHIBITION; ACTIVATION; GLYCOLYSIS; TRANSPORT; MEMBRANE;
Keywords:
ATPase; calcium ion; energy metabolism; erythrocyte; phosphofructokinase deficiency; Tarui's disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Ronquist, G Univ Uppsala Hosp, Dept Clin Chem, S-75185 Uppsala, Sweden Univ Uppsala Hosp Uppsala Sweden S-75185 185 Uppsala, Sweden
Citazione:
G. Ronquist et al., "Familial phosphofructokinase deficiency is associated with a disturbed calcium homeostasis in erythrocytes", J INTERN M, 249(1), 2001, pp. 85-95

Abstract

Objectives. To critically evaluate whether an altered calcium homeostasis in erythrocytes could be contributing to the symptomatology of the Tarui's disease, which is an inherited phosphofructokinase (PFK) deficiency of the muscle isoenzyme, PFK is a tetrameric enzyme with three different isoenzymes, muscle (M), liver (L), and platelet (P). Erythrocytes contain a 50:50 hybrid of M and L type. The deficiency of the muscle isoenzyme displays a symptomatology which is mainly characterized by myopathy, and a compensated haemolytic anaemia. Design. Erythrocyte deformability was assessed before and after autoincubation. Energy related metabolites and energy charge was determined in erythrocytes under various experimental conditions. Setting. The clinical part of the study was performed at the Departments of Cardiology and Clinical Chemistry, Umea University Hospital, and the experimental investigation was carried out at the Department of Clinical Chemistry of the University Hospital of Uppsala, Sweden. Subjects. Four family members with Tarui's disease participated in the study: the proband (patient 1), a 39-year-old male and two siblings, patient 2(male, aged 46 years) and patient 3 (female, 30 pears). Patient 4 (male, 16 years) was the sun of the patient 3. Five healthy persons served as controls (controls 1-5). Interventions. None. Main outcome measures. Cell-physiological variables were determined after autoincubation of erythrocytes (i.e. incubation in their own plasma at 37 degreesC) and after incubation in a composite buffered medium. Results. Erythrocyte deformability as assessed by the erythrocyte fluiditywas substantially decreased in patients compared to the moderate decrease in the control after 24 h of autoincubation, in presence of endogenous Ca2(heparin plasma). Moreover, autoincubation of erythrocytes shows that the patient's erythrocytes, although being moderately deficient in PFK activity, exhibit a normal (or slightly increased) lactate production compared to controls. Despite this, we show an increased ATP turnover with an Ca2+-induced AMP deaminase (and 5'-nucleotidase) activation leading to an increase inhypoxanthine content in patients' erythrocytes of about 100% after 24 h ofautoincubation in heparin plasma, when compared to controls. A loss of volume in patient's erythrocytes after 2 4 h of autoincubation (in presence ofCa2+), as revealed by a diminished MCV, was consistent with an increased metabolic pool of intracellular calcium ions with a selective loss of K+ dueto the activation of the K+ channel by intracellular Ca2+ (Gardos-effect). Conclusion. We conclude that the different calcium ion-induced effects on energy metabolism, structure and function of patients' erythrocytes are dueto an augmented membrane leakage of Ca2+ and therefore an accumulated intracellular Ca2+ pool. This will result in an increased energy demand by the Ca2+ stimulated ATPase (calcium pump) to compensate for the dissipated Ca2gradient across the plasma membrane. The concomitant haemolysis may be explained by a diminished erythrocyte deformability due to Ca2+ overload.

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Documento generato il 29/11/20 alle ore 00:46:25