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Glycolysis

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Glycolysis
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true for glycogen synthesis (glycogenesis) and degradation (glycogenolysis). Many cells store glycogen for the purpose of having glucose available for later use. The liver is less selfish, storing glycogen not for its own use, but for maintenance of blood glucose levels that ensure that other tissues, especially the brain, have an adequate supply of this important substrate. Regulation of the synthesis and degradation of glycogen is a model for our understanding of how hormones work and how other metabolic pathways may be regulated. This subject contributes to our understanding of the diabetic condition, starvation, and how tissues of the body respond to stress, severe trauma, and injury. The Appendix presents the nomenclature and chemistry of the carbohydrates.
Figure 7.2 Overall balanced equation for the sum of the reactions of the glycolytic pathway.
7.2— Glycolysis
Glycolysis Occurs in All Human Cells
The Embden–Meyerhof or glycolytic pathway represents an ancient process, possessed by all cells of the human body, in which anaerobic degradation of glucose to lactate occurs. This is one example of anaerobic fermentation, a term used to refer to pathways by which organisms extract chemical energy from high­energy fuels in the absence of molecular oxygen. For many tissues glycolysis is an emergency energy­yielding pathway, capable of yielding 2 mol of ATP from 1 mol of glucose in the absence of molecular oxygen (Figure 7.2). Thus when the oxygen supply to a tissue is shut off, ATP levels can still be maintained by glycolysis for at least a short period of time. Many examples could be given, but the capacity to use glycolysis as a source of energy is particularly important to the human being at birth. With the exception of the brain, circulation of blood decreases to most parts of the body of the neonate during delivery. The brain is not normally deprived of oxygen during delivery, but other tissues must depend on glycolysis for their supply of ATP until circulation returns to normal and oxygen becomes available again. This conserves oxygen for use by the brain, illustrating one of many mechanisms that have evolved to assure survival of brain tissue in times of stress. Glycolysis sets the stage for aerobic oxidation of carbohydrate. Oxygen is not necessary for glycolysis, and the presence of oxygen can indirectly suppress glycolysis, a phenomenon called the Pasteur effect that is considered later. Nevertheless, glycolysis can and does occur in cells with an abundant supply of molecular oxygen. Provided cells also contain mitochondria, the end product of glycolysis in the presence of oxygen is pyruvate rather than lactate. Pyruvate can then be completely oxidized to CO2 and H2O by enzymes housed within the mitochondria. The overall process of glycolysis plus the subsequent mitochondrial oxidation of pyruvate to CO2 and H2O has the following equation:
Much more ATP is produced in complete oxidation of glucose to CO2 and H2O than in the conversion of glucose to lactate. This has important consequences, which are considered in detail later. For glucose to be completely oxidized to CO2 and H2O, it must first be converted to pyruvate by glycolysis (Figure 7.3). The importance of glycolysis as a preparatory pathway is best exemplified by
Figure 7.3 Glycolysis is a preparatory pathway for aerobic metabolism of glucose. TCA refers to the tricarboxylic acid cycle.
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the brain. This tissue has an absolute need for glucose and processes most of it via glycolysis. Pyruvate produced is then oxidized to CO2 and H2O in mitochondria. An adult human brain uses approximately 120 g of glucose each day in order to meet its need for ATP. In contrast, glycolysis with lactate as the end product is the major mechanism of ATP production in a number of other tissues. Red blood cells lack mitochondria and therefore are unable to convert pyruvate to CO2 and H2O. The cornea, lens, and regions of the retina have a limited blood supply and also lack mitochondria (because mitochondria would absorb and scatter light) and depend on glycolysis as the major mechanism for ATP production. Kidney medulla, testis, leukocytes, and white muscle fibers are almost totally dependent on glycolysis as a source of ATP, because these tissues have relatively few mitochondria. Tissues dependent primarily on glycolysis for ATP production consume about 40 g of glucose per day in a normal adult.
Major dietary sources of glucose are indicated in Chapter 26. Starch is the storage form of glucose in plants and contains a ­1,4­glycosidic linkages along with a ­1,6­
glycosidic branches. Glycogen is the storage form of glucose in animal tissues and contains the same type of glycosidic linkages and branches. Exogenous glycogen refers to that which we eat and digest; endogenous glycogen is that synthesized or stored in our tissues. Exogenous starch or glycogen is hydrolyzed in the intestinal tract with the production of glucose, whereas stored glycogen endogenous to our tissues is converted to glucose or glucose 6­phosphate by enzymes present within the cells. Disaccharides that serve as important sources of glucose in our diet include milk sugar (lactose) and grocery store sugar (sucrose). Hydrolysis of these sugars by enzymes of the brush border of the intestinal tract is discussed on page 1075. Glucose can be used as a source of energy for cells of the intestinal tract. However, these cells do not depend on glucose to any great extent; most of their energy requirement is met by glutamine catabolism (see p. 450). Most of the glucose passes through the cells of the intestinal tract into the portal blood, then the general circulation, to be used by other tissues. Liver is the first major tissue to have an opportunity to remove glucose from the portal blood. When blood glucose is high, the liver removes glucose for the glucose­consuming processes of glycogenesis and glycolysis. When blood glucose is low, the liver supplies the blood with glucose by the glucose­producing processes of glycogenolysis and gluconeogenesis. The liver is also the first organ exposed to the blood flowing from the pancreas and therefore is exposed to the highest concentrations of the hormones released from this endocrine tissue—glucagon and insulin. These important hormonal regulators of blood glucose levels have effects on enzyme­catalyzed steps in the liver.
Glucose Is Metabolized Differently in Various Cells
After penetrating the plasma membrane by mediated transport on the glucose transport protein GLUT­1, glucose is metabolized mainly by glycolysis in red blood cells (Figure 7.4a). Since red blood cells lack mitochondria, the end
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Figure 7.4 Overviews of the major ways in which glucose is metabolized within cells of selected tissues of the body. (a) Glucose transport into the cell by a glucose transport protein (GLUT); (b) glucose phosphorylation by hexokinase; (c) the pentose phosphate pathway; (d) glycolysis; (e) lactic acid transport out of ther cell; (f) pyruvate decarboxylation by pyruvate dehydrogenase; (g) TCA cycle; (h) glycogenesis; (i) glycogenolysis; (j) lipogenesis; (k) gluconeogenesis; (l) hydrolysis of glucose 6­phosphate and release of glucose from the cell into the blood; (m) formation of glucuronides (drug and bilirubin detoxification by conjugation) by the glucuronic acid pathway.
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