Glucose enters the RBC by facilitated diffusion, via the insulin-independent glucose transporter, GLUT-1. The glucose concentration in the RBC is not significantly different from that in plasma, and clinical laboratory measurements of glucose concentration in plasma, serum and whole blood are essentially identical.
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Glycolysis proceeds through a series of phosphorylated intermediates, starting with the synthesis of glucose-6-phosphate (Glc-6-P). During this process, which involves 10 distinct enzymatically catalyzed steps, two molecules of ATP are expended (investment stage) to build up a nearly symmetric intermediate, fructose-1,6-bisphosphate (Fru-1,6-BP), which is then cleaved (splitting stage) to two three-carbon triose phosphates. These are eventually converted into lactate during the yield stage of glycolysis. The yield stage includes both redox and phosphorylation reactions, leading to formation of four molecules of ATP during the conversion of the two triose phosphates into lactate. Two moles of ATP are formed from each mole of triose phosphate, yielding a net 2 moles of ATP per mole of glucose converted into lactate. Glycolysis is a relatively inefficient pathway for extracting energy from glucose: the yield of 2 moles of ATP per mole of glucose is only about 5% of the 36-38 ATP that are available by complete oxidation of glucose to CO2 and H2O in other tissues.
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One might ask why a 10-step pathway is required to convert glucose to lactate - couldn't it have been done in fewer steps? The answer, from a metabolic point of view, is that glycolysis is a central pathway and most glycolytic intermediates serve as branch points to other metabolic pathways. In this way, the metabolism of glucose intersects with the metabolism of fats, proteins and nucleic acids, as well as other pathways of carbohydrate metabolism. Some of these metabolic interactions are shown in Figure 11.2.
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