Carbohydrate Metabolism
The metabolic processes that are ultimately responsible for the eventual production of energy from glucose include glycogenolysis, glycolysis, the pyruvate dehydrogenase © 2009 by Taylor & Francis Group, LLC 30 Nutritional Concerns in Recreation, Exercise, and Sport complex, Krebs cycle, and the electron transport chain. Complete catabolism of glucose for energy yields adenosine triphosphate (ATP), carbon dioxide, and water. Along with that provided by fat catabolism, the energy produced by carbohydrate metabolism is critical for the metabolic processes and muscle contraction needed during the performance of exercise.
General Metabolic Processes of Carbohydrate Metabolism
Carbohydrate for metabolism comes from a variety of sources. These include the diet, via absorption through the intestinal mucosa, glycogen stored primarily in the liver and muscle, and glucose produced from non-glucose precursors via gluconeogenesis. A very limited supply of glucose is also found in the circulation at any given time; however, the concentration of glucose in the bloodstream must be kept relatively constant, so while the glucose present is a critical source of energy for working muscles, it is not a large depot for storage. Glucose serves as a primary fuel for the body and a highly preferred fuel for many cells including the central nervous system and red blood cells. The catabolism of glucose to pyruvate for energy in these cells and all others is called glycolysis.
When athletes need to rapidly produce energy from glucose during very strenuous exercise that can last for only a short time, a large proportion of that glucose will be metabolized anaerobically to produce ATP and the final product, lactic acid (lactate). Lactate is obtained by an anaerobic reaction catalyzed by lactic acid dehydrogenase, which converts pyruvate to lactate. During exercise of a lower intensity, aerobic glucose metabolism will predominate, and although ATP will be produced less rapidly, the final product of glycolysis will be pyruvic acid, which can undergo further metabolism via the pyruvate dehydrogenase complex, followed by Krebs cycle and ultimately the electron transport system to produce additional ATP. If the glucose to be catabolized is found in its storage form as glycogen, the glycogen must first be broken down to glucose derivatives via glycogenolysis. When pyruvate is produced from glucose during aerobic glycolysis, it must first be converted to acetyl CoA prior to further metabolism via Krebs cycle. The pyruvate dehydrogenase (PDH) complex is responsible for this conversion, which along with glycolysis occurs in the cytosol of a cell. The PDH complex requires many enzymes and cofactors to accomplish this process. Cofactors involved include coenzyme A, which includes pantothenic acid as part of its structure, nicotinamide adenine dinucleotide (NAD, a coenzyme form of niacin), flavin adenine dinucleotide (FAD, a coenzyme form of riboflavin), thiamin diphosphate (TDP, coenzyme form of thiamin) as well as magnesium and lipoic acid. During the series of reactions, carbon dioxide is eliminated and NADH H(reduced NAD) is produced, which can be used for ATP synthesis through the electron transport system. Krebs cycle, also known as the citric acid cycle or the tricarboxylic acid (TCA) cycle, is a metabolic pathway that is instrumental in obtaining energy from all macronutrients. In this cyclic pathway, oxaloacetate, produced from pyruvate, accepts the two carbons of acetate from acetyl CoA (produced primarily from carbohydrates and fats via glycolysis and beta-oxidation, respectively) yielding the 6-carbon molecule citrate. Following several intermediate steps, citrate is ultimately converted back to © 2009 by Taylor & Francis Group, LLC Carbohydrates and Fats 31 the 4-carbon molecule oxaloacetate with the loss of two carbons as carbon dioxide. The oxaloacetate is now available to accept two more carbons from acetyl CoA and continue the cycle. Also produced in Krebs cycle is guanosine triphosphate (GTP) and the energy producing equivalents NADH Hand FADH2 (reduced FAD). Like ATP, GTP possesses a high energy bond that when cleaved can produce free energy similarly to that of ATP. NADH Hand FADH2 are further metabolized via the electron transport system to produce ATP. The electron transport system (ETS) accounts for the vast majority of ATP production in the body. The role of the “chain” of molecules in the ETS is to shuttle electrons from one component in the inner mitochondrial membrane to another via a series of oxidation-reduction reactions with the ultimate production of water and ATP from ADP and inorganic phosphorus.
This process has also been termed oxidative phosphorylation. Coenzyme forms of niacin and riboflavin as NADH Hand FADH2 are particularly instrumental in the process, since they serve as the initial electron donators. As described, these molecules are produced in the metabolism of macronutrients by several metabolic pathways including glycolysis, beta-oxidation and Krebs cycle. Glucose that is not needed for energy production can be stored until a time for which it is needed. Glycogen, is a very compact, highly branched chain of glucose molecules linked together by both a-1,4 and a-1,6 glycosidic bonds. The majority of glycogen stored in the body is located in the muscles and liver. In times of energy need, glycogen is broken down via glycogenolysis to produce glucose or glucose derivatives. Glycogen within a muscle cell must be used for energy within that cell, since glycogenolysis continues only until the production of the molecule glucose-6-phosphate in the muscle cell, because muscles lack the enzyme glucose- 6-phosphatase, which produces free glucose from glucose-6-phosphate. Glucose-6- phosphate cannot exit the cell, but can enter the glycolytic pathway within the muscle cell for the production of energy. Glycogen within liver cells can be broken down to free glucose molecules, because the liver produces glucose-6-phosphatase, which removes the phophate molecule. Free glucose can leave the liver cell and travel via the circulation to tissues requiring energy production. During rest, glucose enters the cells via the action of glucose transporters. The GLUT4 transporter is responsible for entry of glucose into muscle cells (as well as the heart and adipose cells) and is activated by the action of the hormone insulin. When activated by insulin, GLUT4 migrates to the cellular membrane to allow for the facilitated diffusion of glucose into the cell. Exercise stimulates the function of GLUT4 transporters thereby enhancing insulin sensitivity; thus, serum concentrations of insulin usually drop during exercise when food is not eaten. Because the demand for glucose by the muscles increases during exercise, glucose is released from the liver in the circulation to allow for uptake by the tissues and production of energy.5 During intensive exercise, blood glucose utilization increases sharply with time and can supply up to 30% of the total energy needed by the muscle, with muscle glycogen supplying most of the remaining energy requirements.6 During prolonged exercise, blood glucose becomes a major contributor as muscle glycogen availability is diminished. Once the liver’s output of glucose fails to sustain the muscle’s glucose uptake, blood glucose levels decrease significantly and might even fall to hypoglycemic values. When carbohydrate stores are depleted work capacity decreases as well.
it can be an important contributor to total glucose availability. Precursors of gluconeogenesis include glycerol (the 3-carbon backbone to acylglycerides such as TGs), lactic acid, pyruvic acid, and many amino acids. The rate of gluconeogenesis is stimulated during exercise to provide glucose to working muscles and other cells. The majority of gluconeogenesis occurs in the liver, as the cells of most tissues do not possess all of the enzymes needed for this process. Other tissues are important providers of gluconeogenic precursors, however. For example, muscles can provide the highly gluconeogenic amino acid alanine from protein catabolism or transamination from pyruvate and glutamate to the liver via the circulation by way of the alanine cycle, and adipose tissue provides fats that contribute glycerol to gluconeogenesis.
The alanine cycle is a series of reactions in which alanine obtained in the muscle from pyruvate through a transamination (pyruvate accepts an amino group from a different amino acid) reaction enters the bloodstream and is taken up by the liver for conversion to glucose. Glucose can be secreted from the liver and then taken up by the muscle, where it again produces pyruvate through glycolysis, which is now available once again for transamination to alanine or for energy production.
During rest, glucose enters the cells via the action of glucose transporters. The GLUT4 transporter is responsible for entry of glucose into muscle cells (as well as the heart and adipose cells) and is activated by the action of the hormone insulin. When activated by insulin, GLUT4 migrates to the cellular membrane to allow for the facilitated diffusion of glucose into the cell. Exercise stimulates the function of GLUT transporters thereby enhancing insulin sensitivity; thus, serum concentrations of insulin usually drop during exercise when food is not eaten. Because the demand for glucose by the muscles increases during exercise, glucose is released from the liver in the circulation to allow for uptake by the tissues and production of energy.
During intensive exercise, blood glucose utilization increases sharply with time and can supply up to 30% of the total energy needed by the muscle, with muscle glycogen supplying most of the remaining energy requirements. During prolonged exercise, blood glucose becomes a major contributor as muscle glycogen availability is diminished. Once the liver’s output of glucose fails to sustain the muscle’s glucose uptake, blood glucose levels decrease significantly and might even fall to hypoglycemic values. When carbohydrate stores are depleted work capacity decreases as well. As carbohydrate stores become depleted, the production of glucose via gluconeogenesis increases. While the rate of gluconeogenesis is typically not considered to be adequate for optimal exercise performance as a sole source of glucose, it can be an important contributor to total glucose availability. Precursors of gluconeogenesis include glycerol (the 3-carbon backbone to acylglycerides such as TGs), lactic acid, pyruvic acid, and many amino acids. The rate of gluconeogenesis is stimulated during exercise to provide glucose to working muscles and other cells. The majority of gluconeogenesis occurs in the liver, as the cells of most tissues do not possess all of the enzymes needed for this process. Other tissues are important providers of gluconeogenic precursors, however.
For example, muscles can provide the highly gluconeogenic amino acid alanine from protein catabolism or transamination from pyruvate and glutamate to the liver via the circulation by way of the alanine cycle, and adipose tissue provides fats that contribute glycerol to gluconeogenesis. The alanine cycle is a series of reactions in which alanine obtained in the muscle from pyruvate through a transamination (pyruvate accepts an amino group from a different amino acid) reaction enters the bloodstream and is taken up by the liver for conversion to glucose. Glucose can be secreted from the liver and then taken up by the muscle, where it again produces pyruvate through glycolysis, which is now available once again for transamination to alanine or for energy production.
