The Energy-Less Red Blood Cell Is Lost: Erythrocyte Enzyme Abnormalities Of Glycolysis

From bloodjournal.hematologylibrary.org by guest on August 26, 2011. For personal use only.

2005 106: 4034-4042 Prepublished online July 28, 2005; doi:10.1182/blood-2005-04-1622

The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis
Richard van Wijk and Wouter W. van Solinge

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From bloodjournal.hematologylibrary.org by guest on August 26, 2011. For personal use only.

Review article

The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis
Richard van Wijk and Wouter W. van Solinge

The red blood cell depends solely on theanaerobic conversion of glucose by the Embden-Meyerhof pathway for the generation and storage of high-energy phosphates, which is necessary for the maintenance of a number of vital functions. Many red blood cell enzymopathies have

been described that disturb the erythrocyte’s integrity, shorten its cellular survival, and result in hemolytic anemia. By far the majority of these enzymopathies arehereditary in nature. In this review, we summarize the current knowledge regarding the genetic, biochemical, and struc-

tural features of clinically relevant red blood cell enzymopathies involved in the Embden-Meyerhof pathway and the Rapoport-Luebering shunt. (Blood. 2005;106: 4034-4042)
© 2005 by The American Society of Hematology

Introduction
The moment the mature red blood cell leaves thebone marrow, it is optimally adapted to perform the binding and transport of oxygen and its delivery to all tissues. This is the most important task of the erythrocyte during its estimated 120-day journey in the bloodstream. The membrane, hemoglobin, and proteins involved in metabolic pathways of the red blood cell interact to modulate oxygen transport, protect hemoglobin from oxidant-induceddamage, and maintain the osmotic environment of the cell. The biconcave shape of the red blood cell provides an optimal area for respiratory exchange. The latter requires passage through microcapillaries, which is achieved by a drastic modification of its biconcave shape, made possible only by the loss of the nucleus and cytoplasmic organelles and, consequently, the ability to synthesize proteins.1During their intravascular lifespan, erythrocytes require energy to maintain a number of vital cell functions. These include (1) maintenance of glycolysis; (2) maintenance of the electrolyte gradient between plasma and red cell cytoplasm through the activity of adenosine triphosphate (ATP)–driven membrane pumps; (3) synthesis of glutathione and other metabolites; (4) purine and pyrimidine metabolism;(5) maintenance of hemoglobin’s iron in its functional, reduced, ferrous state; (6) protection of metabolic enzymes, hemoglobin, and membrane proteins from oxidative denaturation; and (7) preservation of membrane phospholipid asymmetry. Because of the lack of nuclei and mitochondria, mature red blood cells are incapable of generating energy via the (oxidative) Krebs cycle. Instead, erythrocytes...