IN-VIVO METABOLIC STUDIES OF GLUCOSE, ATP AND 2,3-DPG IN BETA-THALASSEMIA-INTERMEDIA, HETEROZYGOUS BETA-THALASSEMIC AND NORMAL ERYTHROCYTES- C-13 AND P-31 MRS STUDIES

C-13 and P-31 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 beta-thalassaemia intermedia, heterozygous beta-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 erythro cytes, the P-31 spectra were comparable between all three blood types, showing similar concentrations of ATP (from 4.5 to 5.2 mu mol/g Hb) a nd 2,3-DPG (from 17.2 to 19.7 mu mol/g Hb). However, the profile of gl ucose metabolism was quite different in beta-thalassaemia intermedia e rythrocytes, where glucose was consumed at a rate of 0.089 +/- 0.035 f mol/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 metabo lism in the thalassaemia intermedia erythrocytes could not be accounte d for by any increase in glucose flux via the Embden-Meyerhof pathway, since no significant difference in 3-C-13-lactate synthesis was obser ved among the three blood types (in units of fmol/cell/h, normal, 0.02 1 +/- 0.013; heterozygous, 0.021 +/- 0.006; beta-thalassaemia intermed ia 0.045 +/- 0.025). These results reflect an accelerated rate of gluc ose metabolism in thalassaemia intermedia erythrocytes because the con tribution of reticulocytes to this altered pattern of metabolism could be excluded. As the only other route of glucose metabolism in erythro cytes is the pentose phosphate pathway (PPP), these results indicate t hat the PPP is more active in beta-thalassaemia intermedia erythrocyte s, perhaps as a consequence of their elevated intracellular oxidative state.