In vivo metabolic studies of glucose, ATP and 2,3‐DPG in β‐thalassaemia intermedia, heterozygous β‐thalassaemic and normal erythrocytes: 13C and 31P MRS studies

Summary. 13 C and 31 P magnetic resonance spectroscopy was used to characterize the in vivo kinetics of glucose metabolism and intracellular ATP and 2,3‐DPG concentrations in erythrocytes obtained from β‐thalassaemia intermedia, heterozygous β‐thalassaemic and normal individuals and maintained in suspension. Except for an upfield chemical shift in the 2P and 3P resonance of 2,3‐DPG in the thalassaemia intermedia erythrocytes, the 31 P spectra were comaparable between all three blood types, showing similar concentrations of ATP (from 4.5 to 5.2 μmol/g Hb) and 2,3‐DPG (from 17.2 to 19.7 μmol/g Hb). However, the profile of glucose metabolism was quite different in β‐thalassaemia intermedia erythrocytes, where glucose was consumed at a rate of 0.089 ± 0.035 fmol/cell/h, significantly higher than that of normal (0.032 ± 0.018 fmol/cell/h; P = 0.01) and heterozygous (0.025 ± 0.004 fmol/cell/h; P = 0.01) erythrocytes. This near 3‐fold faster rate of glucose metabolism in the thalassaemia intermedia erythrocytes could not be accounted for by any increase in glucose flux via the Embden‐Meyerhof pathway, since no significant difference in 3‐ 13 C‐lactate synthesis was observed among the three blood types (in units of fmol/cell/h, normal, 0.021 ± 0.013; heterozygous, 0.021 ± 0.006; β‐thalassaemia intermedia 0.045 ± 0.025). These results reflect an accelerated rate of glucose metablolism in thalassaemia intermedia erythrocytes because the contribution of reticulocytes to this altered pattern of metabolism could be excluded. As the only other route of glucose metabolism in erythrocytes is the pentose phosphate pathway (PPP), these results indicate that the PPP is more active in β‐thalassaemia intermedia erythrocytes, perhaps as a consequence of their elevated intracellular oxidative state.