Glucose is the major carbohydrate on Earth, the backbone and monomer unit of cellulose and starch. It is also the only fuel that is used by all cells in our body. All of these cells, even the microbes in our intestines, begin the metabolism of glucose by a pathway termed glycolysis, i.e. carbohydrate (glyco) splitting (lysis). Glycolysis is catalyzed by soluble cytosolic enzymes and is the ubiquitous, central metabolic pathway for glucose metabolism. The erythrocyte, commonly known as the red blood cell (RBC), is unique among all cells in the body - it uses glucose and glycolysis as its sole source of energy. Thus, the RBC is a useful model for an introduction to glycolysis.
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| Pyruvate, a three-carbon acid, is the end product of glycolysis; 2 moles of pyruvate are formed per mole of glucose. In cells with mitochondria and oxidative metabolism, pyruvate is converted completely into CO2 and H2O - glycolysis in this oxidative setting is termed aerobic glycolysis. In RBCs, which lack mitochondria and oxidative metabolism, pyruvate is reduced to lactic acid, a three-carbon hydroxyacid, the product of anaerobic glycolysis. Each mole of glucose yields 2 moles of lactate, which are then excreted into blood. Two molecules of lactic acid contain exactly the same number of carbons, hydrogens, and oxygens as one molecule of glucose (Fig. 11.1); however, there is sufficient free energy available from the cleavage and rearrangement of the glucose molecule to produce 2 moles of ATP per mole of glucose converted into lactate. The RBC uses most of this ATP to maintain electrochemical and ion gradients across its plasma membrane.
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| In the red cell, 10-20% of the glycolytic intermediate, 1,3-bisphosphoglycerate, is diverted to the synthesis of 2,3-bisphosphoglycerate (2,3-BPG), an allosteric regulator of the O2 affinity of Hb. The pentose phosphate pathway, a shunt from glycolysis, accounts for about 10% of glucose metabolism in the red cell. In the red cell this pathway has a special role in protection against oxidative stress, while in nucleated it also serves as a source of NADPH for biosynthetic reactions and pentoses for nucleic acid synthesis.
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