Favism: Erythrocyte Metabolism during Haemolysis and Reticulocytosis

Abstract

The reduced activity of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate; NADP+ I-oxidoreductase; G6PD) in Mediterranean erythrocytes explains the precarious equilibrium of the hexose monophosphate pathway (HMP) and the susceptibility of these cells to hemolytic agents. G6PD-deficient erythrocytes, in steady-state conditions, have a low NADPH/NADP+ ratio, allowing the HMP to operate at its maximal intracellular rate and to compensate the intrinsic erythrocyte enzyme deficiency. Studies started soon after accidental intake of fava beans by sensitive G6PD-deficient subjects demonstrate a decrease of NADPH/NADP+ ratio and reduced glutathione. The metabolic effects induced by fava beans may be attributed to oxidative stress probably associated with an inhibitor effect of some unknown metabolite on the HMP. The availability of erythrocytes from subjects recovering from hemolysis with high reticulocyte counts and increased G6PD activity, provided new information on the rate of synthesis and on the in vivo decay of the mutant enzyme. Correlation of G6PD activity to reticulocyte count and extrapolation to an ideally homogenous population of reticulocytes revealed that the mutant enzyme was synthesized at a nearly normal rate. The present correlation allows an estimate of the in vivo half-life of Mediterranean G6PD. The rate of decline of about 8 days observed in this study well correlates to the intracellular metabolic aspects of G6PD Mediterranean erythrocytes.