Human erythrocyte metabolism is modulated by the O2‐linked transition of hemoglobin

The metabolic behaviour of human erythrocytes has been investigated with particular regard to the effect of their oxygenation state. Experiments performed at high phosphate concentration (80 mM) within the pH range 7.0–7.8 on erythrocytes at high (HOS) and low (LOS) oxygen saturation showed that at any pH value: (1) glucose consumption was independent of the oxygenation state; (2) pentose phosphate pathway (PPP) flux was about 2 times higher in the HOS than in the LOS state. At low phosphate concentration (1.0 mM) the PPP flux doubled in HOS as well as in LOS erythrocytes, whereas the decrease in glucose consumption was more marked in the HOS state. Metabolism of LOS erythrocytes approached that of HOS erythrocytes under the following conditions: (1) erythrocytes having band 3 modified by 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid; (2) CO‐saturated erythrocytes. These data support the hypothesis of a modulation of the relative rates of PPP and glycolysis achieved through competition between deoxy‐hemoglobin (deoxy‐Hb) and glycolytic enzymes for the cytoplasmic domain of band 3.

[1]  G. Chetrite,et al.  Affinity of hemoglobin for the cytoplasmic fragment of human erythrocyte membrane band 3. Equilibrium measurements at physiological pH using matrix-bound proteins: the effects of ionic strength, deoxygenation and of 2,3-diphosphoglycerate. , 1985, Journal of molecular biology.

[2]  I. Messana,et al.  The multiple functions of hemoglobin. , 1995, Critical reviews in biochemistry and molecular biology.

[3]  P. Low Structure and function of the cytoplasmic domain of band 3: center of erythrocyte membrane-peripheral protein interactions. , 1986, Biochimica et biophysica acta.

[4]  R. Labotka Measurement of intracellular pH and deoxyhemoglobin concentration in deoxygenated erythrocytes by phosphorus-31 nuclear magnetic resonance. , 1984, Biochemistry.

[5]  P. Low,et al.  The interaction of hemoglobin with the cytoplasmic domain of band 3 of the human erythrocyte membrane. , 1984, The Journal of biological chemistry.

[6]  N. Hamasaki,et al.  Effect of oxygen tension on glycolysis in human erythrocytes. , 1970, Journal of biochemistry.

[7]  J. Murphy Erythrocyte metabolism. II. Glucose metabolism and pathways. , 1960, The Journal of laboratory and clinical medicine.

[8]  M. Jennings,et al.  Anion transport across the erythrocyte membrane, in situ proteolysis of band 3 protein, and cross-linking of proteolytic fragments by 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonate. , 1979, Biochimica et Biophysica Acta.

[9]  J. M. Salhany Band 3 quaternary states and allosteric control of function , 1992 .

[10]  S. Rapoport,et al.  Response of the glycolysis of human erythrocytes to the transition from the oxygenated to the deoxygenated state at constant intracellular pH. , 1976, Biochimica et biophysica acta.

[11]  P. Low,et al.  Regulation of glycolysis via reversible enzyme binding to the membrane protein, band 3. , 1993, The Journal of biological chemistry.