Erythroid glucose transport in health and disease

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INVITED REVIEW

Erythroid glucose transport in health and disease Hélène Guizouarn 1

&

Benoit Allegrini 1

Received: 6 February 2020 / Revised: 15 May 2020 / Accepted: 22 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Glucose transport is intimately linked to red blood cell physiology. Glucose is the unique energy source for these cells, and defects in glucose metabolism or transport activity are associated with impaired red blood cell morphology and deformability leading to reduced lifespan. In vertebrate erythrocytes, glucose transport is mediated by GLUT1 (in humans) or GLUT4 transporters. These proteins also account for dehydroascorbic acid (DHA) transport through erythrocyte membrane. The peculiarities of glucose transporters and the red blood cell pathologies involving GLUT1 are summarized in the present review. Keywords Erythrocyte . Glucose . GLUT1 . Red blood cell . Stomatocytosis

Introduction What makes red blood cell glucose transport relevant to dedicate a review on this topic? Red blood cells could be described as corpuscles devoted to organism respiration, carrying and delivering oxygen to tissues and simultaneously transporting a significant part of the CO2 produced in these tissues back to the lung. This simplified vision of erythrocyte physiology does not preclude the complexity of this cell, which is able to withstand considerable physical constraints throughout cardiovascular circulation and is interacting with various cells, but it helps to understand which role glucose plays in its physiology. Binding, transporting and delivering oxygen is largely improved if this oxygen is not dissipated by metabolism. Red blood cells (RBCs), whether nucleated as in most vertebrates or not, like in mammals, are devoid of mitochondria and have developed to obtain energy only through glycolysis and pentose phosphate pathway (PPP) (Fig. 1). Glycolysis provides the ATP, essential to fuel the ion pumps Na+/K+ ATPase and calcium ATPase but also to control the phosphorylation of cytoskeleton a crucial determinant of RBC shape. In addition This article is part of the special issue on Glucose Transporters in Health and Disease in Pflügers Archiv—European Journal of Physiology * Hélène Guizouarn [email protected] 1

Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose, 28 av. Valrose, 06100 Nice, France

to ATP, glycolysis yields the nicotinamide adenine dinucleotide, NADH, a powerful reducing agent that prevents haem oxidation, keeping ferrous in its reduced Fe2+ state. RBCs are particularly exposed to reactive oxygen species (ROS), and besides NADH, their major defence against ROS is given by the anti-oxidant glutathione, which redox state depends on the PPP. The shuttle between glycolysis and pentose pathway is regulated by the enzyme glucose-6-phosphate dehydrogenase (G6PD) that diverts the glucose-6-phosphate from glycolysis to yield other hexose monophosphates (Fig. 1). This conversion allows the reduction of nicotinamide adenine dinucleotide phosph