Chapter 34 Carbohydrate Metabolism Carbohydrate metabolism is important for both plants and animals. Introduction to General, Organic, and Biochemistry, 10e John Wiley & Sons, Inc Morris Hein, Scott Pattison, and Susan Arena
Course 34.1 Metabolic Pathways 34.2 Exercise and Energy Metabolism 34.3 Carbohydrate Metabolism and Cooperation 34.4 Anaerobic Sequence 34.5 Citric Acid Cycle (Aerobic Sequence) 34.6 Gluconeogenesis 34.7 Overview of Complex Metabolic Pathways 2
Course 34.8 Hormones 34.9 Blood Glucose and Hormones Chapter 34 Summary 3
Metabolic Pathways Biochemists define a metabolic pathway as a series of biochemical reactions that serve a specific purpose. Every cell contains thousands of reactions comprising many metabolic pathways. A select group of pathways provides cellular energy using carbohydrates as the energy source. 4
Metabolic Pathways Sunlight provides the energy that is stored in carbohydrates. The equation below summarizes the production of glucose (a carbohydrate) and oxygen by the endothermic process called photosynthesis. During photosynthesis carbon atoms from carbon dioxide are reduced and oxygen atoms from water are oxidized. Light energy is used to cause a net movement of electrons from water to carbon dioxide. 5
Metabolic Pathways The equation below represents the oxidation of glucose and corresponds to the reversal of the overall photosynthesis process. Electrons move from carbohydrate carbons to oxygen. Energy stored in the reduced carbon atoms in glucose is released (2820 kj) and can be used by the cell to do work. 6
Metabolic Pathways Like photosynthesis, the overall process of glucose oxidation proceeds by a series of enzyme-catalyzed reactions. These reactions channel the liberated energy into heat production and into the formation of ATP. 7
Your Turn! Fill in the blanks with oxidized or reduced in the statements below. Carbon atoms in carbohydrates are and oxygen atoms in oxygen are to form carbon dioxide and water during the production of cellular energy. During photosynthesis carbon atoms in carbon dioxide are and oxygen atoms in water are to form carbohydrates and oxygen. 8
Your Turn! Fill in the blanks with oxidized or reduced in the statements below. Carbon atoms in carbohydrates are oxidized and oxygen atoms in oxygen are reduced to form carbon dioxide and water during the production of cellular energy. During photosynthesis carbon atoms in carbon dioxide are reduced and oxygen atoms in water are oxidized to form carbohydrates and oxygen. 9
Exercise and Energy Metabolism The basal metabolic rate is the rate of energy consumption for an individual that is at rest. We use more energy than the basal metabolic rate when we carry out any mental or physical work. Typically the basal metabolic rate may represent roughly 70% of the total energy expenditure on a day-to-day basis. 10
Exercise and Energy Metabolism The basal metabolic rate for skeletal muscle is about 13 kcal/kg muscle mass/day. Muscle tissue is able to maintain a small reserve of high-energy phosphate bonds in the form of ATP. Muscle tissue can contract for no more than a few seconds before the supply of high-energy phosphate bonds is depleted. Muscles use glycogen as the next energy source. This polymer breaks down to glucose which is oxidized to replenish the ATP supply. 11
Exercise and Energy Metabolism The energy from glycogen is useful only for about two minutes of work. Muscles build up lactic acid when glycogen stores are depleted. In humans the liver organ replenishes the muscle glucose supply and removes lactic acid. Muscle contractions can continue with help from the liver, but the rate of contraction is slowed further as muscle cells wait for glucose transport. Carbohydrates, and glucose in particular, are key components of overall energy metabolism. 12
Carbohydrate Metabolism and Cooperation Carbohydrate metabolism is the sum of all chemical reactions found in living organisms that form, destroy, and interconvert carbohydrates. A proper functioning of carbohydrate metabolism requires both coordination among many different metabolic pathways within cells and cooperation among many different cell types. Glucose is the most important carbohydrate in metabolism. 13
Carbohydrate Metabolism and Cooperation Glucose can be metabolized either with oxygen (aerobically) or without oxygen (anaerobically). In the presence of molecular oxygen glucose is oxidized to carbon dioxide. This process is the most efficient means of energy production and provides greater than 90% of all ATP for a typical cell. Glucose can also be used to make ATP when little or no oxygen is available. In humans this anaerobic process produces lactic acid. 14
Carbohydrate Metabolism and Cooperation All human cells can use glucose for energy but each cell type, tissue, or organ may use glucose in a different way. Most important the brain is almost totally dependent on glucose for energy. Skeletal muscle also has a requirement for glucose but only when the muscle is contracting under anaerobic conditions. Other organs use other molecules such as fatty acids, lactate, amino acids for energy. 15
Carbohydrate Metabolism and Cooperation A good example of organ cooperation in carbohydrate metabolism occurs between skeletal muscle and the lungs during skeletal muscle work. The production of CO2 by skeletal muscle increases blood acidity. Energy use at the muscle Gas balance restored at the lungs - O 2 removed from the bloodstream - O 2 inhaled - More O 2 released from hemoglobin - More O 2 binds to hemoglobin - CO 2 released into the bloodstream - CO 2 exhaled - Blood acidity increases - Blood acidity decreases 16
Carbohydrate Metabolism and Cooperation Another example of organ cooperation occurs between skeletal muscle and the liver. The production of lactic acid also increases blood acidity. Energy use at the muscle Nutrient balance restored at the liver - Glucose removed from the bloodstream - Glucose released to bloodstream - Lactate released to the bloodstream - Lactate removed from bloodstream 17
Carbohydrate Metabolism and Cooperation A diagram describing the cooperation between the liver, lungs, and muscle during carbohydrate metabolism is below. 18
Carbohydrate Metabolism and Cooperation Carbohydrate metabolism can be significantly impaired if coordination among organs fails. Loss of the hormone insulin, in diabetes mellitus results in severe damage to glucose metabolism and can result in abnormally high blood glucose levels (hyperglycemia). Coordination also may be lost when the liver is damaged which can result in low blood sugar (hypoglycemia). 19
Carbohydrate Metabolism and Cooperation Every cell contains chemical reactions that use and/or produce glucose. These chemical reactions join together to form pathways that serve a common purpose. Some pathways are used to provide ATP. Catabolic pathways are shown in red in the diagram. Others are used to synthesize glucose and are anabolic shown in green in the diagram. 20
Carbohydrate Metabolism and Cooperation Under anaerobic conditions, a sequence of reactions known as the Embden Meyerhof pathway oxidizes glucose. If molecular oxygen is available (under aerobic conditions), the citric acid cycle works with this pathway to completely oxidize glucose to carbon dioxide. 21
Carbohydrate Metabolism and Cooperation The anabolic pathway gluconeogenesis responsible for making glucose. This pathway is particularly important in the liver. When blood glucose is in excess, it is converted to glycogen in the liver and muscle tissue in a process called glycogenesis. When glucose is needed glycogen is broken down in a process known as glycogenolysis. 22
Carbohydrate Metabolism and Cooperation These processes are shown together here. 23
Your Turn! Label the following processes as catabolic or anabolic. Glycogenesis The Embden Meyerhof pathway or glycolysis Gluconeogenesis Glycogenolysis Formation of CO 2 during the citric acid cycle 24
Your Turn! Label the following processes as catabolic or anabolic. Glycogenesis (glycogen produced from glucose): anabolic The Embden Meyerhof pathway or glycolysis (anaerobic conversion of glucose to pyruvate): catabolic Gluconeogenesis (formation of glucose from lactate): anabolic Glycogenolysis (formation of glucose from glycogen): catabolic Formation of CO 2 during the citric acid cycle: catabolic 25
Your Turn! Skeletal muscle produces carbon dioxide and lactic acid during contraction which causes the blood to become more acidic. Why does this cause the blood to become acidic? 26
Your Turn! Skeletal muscle produces carbon dioxide and lactic acid during contraction which causes the blood to become more acidic. Why does this cause the blood to become acidic? Carbon dioxide reacts with water in the blood to form carbonic acid which is an acid. Lactic acid is a carboxylic acid. 27
Anaerobic Sequence The anaerobic conversion of glucose to pyruvate is known as the Embden Meyerhof pathway. The sequence of ten steps is catabolic during which glucose is oxidatively degraded to form pyruvate. 28
Anaerobic Sequence During the Embden Meyerhof pathway glucose is oxidized and broken down and two NAD + coenzymes are reduced to two NADH. In addition the net production of ATP during this pathway is two ATP molecules. This pathway can be broken down into three parts as shown on the following slide. Preparatory phase Oxidation reaction ATP production phase 29
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Anaerobic Sequence The Embden Meyerhof pathway is the only means for human cells to produce ATP in the absence of molecular oxygen. In the absence of oxygen, pyruvate is converted to lactate in muscle cells to regenerate NAD + for the pathway. When lactate is the final product of anaerobic glucose catabolism, the pathway is termed glycolysis. 31
Anaerobic Sequence In yeast cells, pyruvate is converted to acetaldehyde instead of lactate which is then reduced to ethanol to regenerate NAD + for the Embden Meyerhof pathway. 32
Anaerobic Sequence The net result of the Embden Meyerhof pathway is shown below. This anaerobic pathway is not very efficient. We see that this pathway releases less than one-tenth of the total energy available in glucose when compared to the complete oxidation of glucose under aerobic conditions. 33
Your Turn! Overall two molecules of ATP are produced from one glucose molecule during the Embden Meyerhof pathway. Indicate the number of ATP molecules consumed and produced during each part of this pathway to result in this net ATP production. Preparatory phase: Oxidation reaction: ATP production phase: 34
Your Turn! Preparatory phase: Two ATP consumed 35
Your Turn! Oxidation reaction: ATP neither consumed nor produced 36
Your Turn! ATP production phase: Four ATP produced 37
Your Turn! There is only one redox reaction in the Embden Meyerhof pathway. What reaction is this? 38
Your Turn! There is only one redox reaction in the Embden Meyerhof pathway. What reaction is this? This is the Oxidation Reaction that follows the Preparatory Phase. 39
Your Turn! The Oxidation Reaction and the reactions in the ATP Production Phase occur twice to degrade one glucose molecule. Why? 40
Your Turn! The Oxidation Reaction and the reactions in the ATP Production Phase occur twice to degrade one glucose molecule. Why? Two glyceraldeyde-3-phosphate molecules are produced from one glucose molecule during the Preparatory Phase. A single glyceraldeyde-3-phosphate molecule is oxidized during each pass through the Oxidation Reaction and the product of this reaction proceeds through to ATP production. 41
Your Turn! 1,3-Bisphosphoglycerate and phospoenolpyruvate both transfer phosphate groups to ADP to form ATP during the ATP Production Phase. Is this an example of substrate-level phosphorylation? 42
Your Turn! Yes. This is substrate-level phosphorylation. Recall that substrate-level phosphorylation is the process whereby energy derived from oxidation is used to form highenergy phosphate bonds on various biochemical molecules (substrates) and where the biochemical substrates transfer phosphate to ADP to form ATP. 43
Your Turn! How many moles of pyruvate and how many moles of ATP are produced from 0.75 moles of glucose during the Embden Meyerhof pathway? 44
Your Turn! How many moles of pyruvate and how many moles of ATP are produced from 0.75 moles of glucose during the Embden Meyerhof pathway? Recall that two moles of pyruvate and two moles of ATP are produced from one mole of glucose (see equation below). Therefore 1.50 moles of pyruvate and 1.50 moles of ATP are produced from 0.75 moles of glucose. 45
Citric Acid Cycle (Aerobic Sequence) The lactate formed during glycolysis may be: circulated back to the liver and converted to glycogen at the expense of some ATP, or converted back to pyruvate in order to enter the citric acid cycle. 46
Citric Acid Cycle (Aerobic Sequence) Pyruvate is the link between the anaerobic Embden Meyerhof pathway and the aerobic sequence (citric acid cycle). Pyruvate does not enter into the citric acid cycle. It is first converted to acetyl coenzyme A (acetyl-coa). 47
Citric Acid Cycle (Aerobic Sequence) Acetyl coenzyme A consists of an acetyl group bonded to a coenzyme A group. Acetyl coenzyme A contains the following units. The acetyl group is oxidized during the citric acid cycle. Coenzyme A is abbreviated as CoASH or CoA. Acetyl coenzyme A is abbreviated as acetyl-coa or acetyl- SCoA. 48
Citric Acid Cycle (Aerobic Sequence) The citric acid cycle (the Krebs cycle) is a series of eight reactions in which the acetyl group of acetyl-coa is oxidized to form carbon dioxide and water. The reduced coenzymes NADH and FADH 2 are also formed during this cycle which pass electrons through the electron-transport system resulting in the production of ATP. The citric acid cycle occurs in mitochondria which are the primary sites for the production of cellular energy. 49
Citric Acid Cycle (Aerobic Sequence) The citric acid cycle produces little usable cellular energy directly (except for GTP, guanosine triphosphate). The reduced coenzymes produce by the cycle are used by electron transport and oxidative phosphorylation to produce a majority of the ATP. The citric acid cycle is aerobic because it depends on electron transport which uses oxygen. 50
Citric Acid Cycle (Aerobic Sequence) The citric acid cycle, electron transport, and oxidative phosphorylation produce energy for the cell and take place in the mitochondria. Overall, these processes result in the oxidation of one pyruvate ion to form three carbon dioxide molecule (with the formation of a maximum of 15 ATP molecules). 51
Citric Acid Cycle (Aerobic Sequence) A large quantity of energy (1260 kj) becomes available to the cell when pyruvate is fully oxidized. Most of this energy is used to reduce coenzymes. These coenzymes, in turn, yield a total of 14 ATP molecules via mitochondrial electron transport and oxidative phosphorylation. 52
Citric Acid Cycle (Aerobic Sequence) The total energy yield from one molecule of glucose is shown here. This tabulation includes the one ATP molecule from one GTP molecule in the citric acid cycle. The citric acid cycle is shown on the following slide... 53
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Your Turn! How many moles of NADH and FADH 2 are obtained when 2.75 moles of pyruvate are converted to acetyl- CoA and then oxidized in the citric acid cycle? 55
Your Turn! How many moles of NADH and FADH 2 are obtained when 2.75 moles of pyruvate are converted to acetyl- CoA and then oxidized in the citric acid cycle? 4 moles of NADH and 1 mole of FADH 2 are produced from 1 mole of pyruvate. Therefore 11 moles of NADH and 2.75 moles of FADH 2 are produced from 2.75 moles of pyruvate. 56
Gluconeogenesis A continuous supply of glucose is needed by the body. The amount of glucose and glycogen present in the body will last for only about four hours. There is a metabolic need for a pathway that produces glucose from noncarbohydrate sources. The formation of glucose from noncarbohydrate sources is called gluconeogenesis. 57
Gluconeogenesis Most of the glucose formed during gluconeogenesis comes from lactate, certain amino acids (after deamination) and the glycerol from fats. Gluconeogenesis takes place primarily in the liver and also in the kidneys. The liver is primarily responsible for maintaining normal blood-sugar levels. 58
Your Turn! Phosphoenolpyruvate and glyceraldehyde are produced from lactate, amino acids and glycerol which are then converted to glucose during gluconeogenesis. These two compounds are intermediates in which metabolic pathway? 59
Your Turn! Phosphoenolpyruvate and glyceraldehyde are intermediates in the Embden Meyerhof pathway. 60
Overview of Complex Metabolic Pathways The Embden Meyerhof pathway and the citric acid cycle are complex. Many of the chemicals that form in the middle of a pathway (pathway intermediates) are also used in other metabolic processes within the cell. 61
Overview of Complex Metabolic Pathways For example: Glucose-6-phosphate is an intermediate in the Embden Meyerhof pathway and is used to make ribose. α-ketoglutarate is an intermediate in the citric acid cycle and is also used to make the amino acid L- glutamic acid. 62
Overview of Complex Metabolic Pathways The multiple-step pathways help cells to handle metabolic energy efficiently. Cells extract only a little energy from glucose during each chemical reaction. The quantity of energy released in each step is small enough to be handled by the cell. The metabolic pathways must have a number of steps for a cell to extract the maximum amount of energy. 63
Overview of Complex Metabolic Pathways A single-step oxidation process compared with a multiplestep process. In the pathway, A, B, and C represent hypothetical pathway intermediates. 64
Overview of Complex Metabolic Pathways The actual energy change for each reaction in the Embden Meyerhof path is shown here. 65
Hormones Hormones are chemical substances that act as control agents in the body, often regulating metabolic pathways. Hormones help to adjust physiological processes such as digestion, metabolism, growth, and reproduction. Hormones are often called the chemical messengers of the body. They do not fit into any single chemical structural classification. Many are proteins or polypeptides, some are steroids, and others are phenol or amino acid derivatives. 66
Hormones Because a lack of any hormone often produces serious physiological disorders, many hormones are produced synthetically or are extracted from their natural sources for medical purposes. A number of hormones and their functions are listed on the following slide... 67
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Hormones The structures of some hormones are shown here. 69
Blood Glucose and Hormones An adequate blood-glucose level must be maintained to ensure good health. Hormones regulate and coordinate metabolism in specific organs to achieve this goal. Glucose concentrations average about 70 100 mg/100 ml of blood under normal fasting conditions. 70
Blood Glucose and Hormones Hyperglycemia exists when glucose concentration rises above the normal level. Renal threshold is reached when blood glucose levels reach 140 170 mg/100 ml of blood. Hypoglycemia exists when the glucose concentration of the blood goes below the normal fasting level. 71
Blood Glucose and Hormones Glucose concentration in the blood is under the control of various hormones. These hormones act as checks on one another and establish an equilibrium condition called homeostasis. Three hormones are of special significance in maintaining the glucose concentration within the proper limits. insulin epinephrine (adrenaline) glucagon 72
Blood Glucose and Hormones Insulin reduces blood-glucose levels by increasing the rate of glycogen formation. Epinephrine and glucagon increase the rate of glycogen breakdown (glycogenolysis) and increase blood-glucose levels. In healthy individuals these reactions keep glucose levels in balance. 73
Blood Glucose and Hormones Type 1 diabetes mellitus (also known as juvenile-onset or insulin-dependent diabetes) is a serious metabolic disorder characterized by hyperglycemia, glycosuria (glucose in the urine), frequent urination, thirst, weakness, and loss of weight. A glucose-tolerance test can be used to determine a person s tolerance for glucose. The test is conducted by analyzing blood and urine specimens over a period of time from a person who has ingested glucose. Results of such a test are shown on the following slide... 74
Blood Glucose and Hormones 75
Your Turn! Explain why insulin, which is a protein, must be given by injection and can t be taken orally. 76
Your Turn! Explain why insulin, which is a protein, must be given by injection and can t be taken orally. Proteins are sensitive to acid hydrolysis. Insulin would be hydrolyzed to amino acids in the gastrointestinal tract if taken orally. 77
Chapter 34 Summary A metabolic pathway is a series of biochemical reactions that serve a specific purpose. Photosynthesis is an example of an anabolic pathway. It uses sunlight to make glucose from carbon dioxide. The basic energy to maintain life is the basal metabolic rate. ATP provides an immediately available energy. 78
Chapter 34 Summary Carbohydrate metabolism is the sum of all chemical reactions found in living organisms that form, destroy, and interconvert carbohydrates. Glucose is very important in carbohydrate metabolism. Different human tissues cooperate in order to balance carbohydrate metabolism. Diseases that impair tissue cooperation have a large impact on carbohydrate metabolism. 79
Chapter 34 Summary Glucose supplies metabolic energy via several catabolic pathways. The anabolic pathway, gluconeogenesis, produces glucose. The Embden Meyerhof multi-step pathway is the anaerobic conversion of glucose to pyruvate. Glycolysis produces lactate from glucose by combining the Embden Meyerhof pathway with a reaction that 80 reduces pyruvate to lactate.
Chapter 34 Summary Pyruvate is used by the citric acid cycle after being converted to acetyl-coa. The citric acid cycle is a cyclic metabolic pathway that converts the acetate carbons of acetyl-coa to carbon dioxide. Gluconeogenesis is the formation of glucose from noncarbohydrate precursors. Multiple-step metabolic pathways are advantageous to life. 81
Chapter 34 Summary Hormones are chemical substances that act as control agents in the body, often regulating metabolic pathways. The hormones insulin, glucagon, and epinephrine are primarily responsible for maintaining a self-regulated equilibrium (homeostasis) for blood glucose. 82