Chapter 1 Title of Chapter

Chapter 7 – Metabolism: Transformations and Interactions

Learning Objectives After completing Chapter 7, the student will be able to: 1. Discuss the chemical reactions that occur within the body, including metabolism, anabolism, and catabolism. 2. Describe how carbohydrates, proteins, and fats are used to meet the energy needs of the body. 3. Explain the process of glycolysis. 4. Explain the process of deamination and the synthesis of non-essential amino acids. 5. Discuss the TCA cycle and the electron transport chain. 6. Explain what happens in the body during feasting and fasting. 7. Discuss the term moderation in reference to alcohol consumption. 8. Explain how the body metabolizes alcohol. 9. Discuss the role of the liver in alcohol metabolism. 10. Discuss the short- and long-term effects of alcohol on health.

Lecture Presentation Outline

I. Chemical Reactions in the Body Plants use the sun’s energy to make carbohydrate from carbon dioxide and water. This is called photosynthesis. Humans and animals eat the plants and use the carbohydrate as fuel for their bodies. During digestion, the energy-yielding nutrients are broken down to monosaccharides, fatty acids, glycerol, and amino acids. After absorption, enzymes and coenzymes can build more complex compounds. In metabolism they are broken down further into energy (ATP), water, and carbon dioxide.

A. Metabolic reactions take place inside of cells, especially liver cells. B. Anabolism is the building up of body compounds and requires energy. C. Catabolism is the breakdown of body compounds and releases energy. D. The Transfer of Energy in Reactions—ATP 1. A high-energy compound called adenosine triphosphate (ATP) is made. 2. Coupled reactions are chemical reactions that occur simultaneously. E. Enzymes and coenzymes are helpers in reactions. 1. Enzymes are protein catalysts that cause chemical reactions. 2. Coenzymes are organic molecules that function as enzyme helpers. 3. Cofactors are organic or inorganic substances that facilitate enzyme action.

II. Breaking Down Nutrients for Energy The breakdown of glucose to energy starts with glycolysis to pyruvate. Pyruvate may be converted to lactic acid anaerobically (without oxygen) and acetyl CoA aerobically (with oxygen). Eventually, all energy-yielding nutrients enter the TCA cycle or tricarboxylic acid cycle (or Kreb’s cycle) and the electron transport chain.

A. Glucose 1. Glucose-to-pyruvate is called glycolysis or glucose splitting. 2. Pyruvate’s Options—Anaerobic or Aerobic a. Anaerobic – lactate. b. Aerobic – acetyl CoA. 3. Pyruvate-to-Lactate a. Oxygen is not available or cells lack sufficient mitochondria. b. Lactate is formed when hydrogen is added to pyruvate. c. Liver cells recycle muscle lactic acid through the Cori cycle. 4. Pyruvate-to-acetyl CoA is irreversible. 5. Acetyl CoA’s Options a. Synthesize fats when the body has enough ATP. b. Generate ATP when the cell is low in energy. B. Glycerol and Fatty Acids 1. The conversion of glycerol to pyruvate is easy because they are both three-carbon compounds. 2. Fatty acids-to-acetyl CoA reactions are called fatty acid oxidation. 3. Fatty acids cannot be used to synthesize glucose. Glucose must be available to provide energy to the red blood cells, brain, and nervous system. C. Amino Acids 1. Amino acids can be converted energy. 2. Amino acids are a fairly good source of glucose when carbohydrate is not available. D. Breaking Down Nutrients for Energy—In Summary 1. Glucose and fatty acids are primarily used for energy, amino acids to a lesser extent. 2. Glucose is made from all carbohydrates, most amino acids, and the glycerol portion of fat. 3. Protein is made from amino acids. 4. Glucose can be made into nonessential amino acids if nitrogen is present. 5. All energy-yielding nutrients consumed in excess can contribute to fat storage. E. The Final Steps of Catabolism 1. The TCA cycle contains a 4-carbon compound called oxaloacetate that has a critical role. 2. The Electron Transport Chain a. Consumes oxygen. b. Produces carbon dioxide and water. c. Produces energy as ATP. 3. The kCalories-per-Gram Secret Revealed a. Fat provides 9 kcal/gram. b. Carbohydrate provides 4 kcal/gram. c. Protein provides 4 kcal/gram. d. Fat provides more energy because the bonds in fat molecules are easily oxidized and result in more ATP.

III. Energy Balance When energy intake exceeds energy output, there is a gain in weight. Excess energy can come from protein, fat, or carbohydrate. Fat is the most efficiently stored as fat.

A. Feasting—Excess Energy 1. Excess protein is converted to fat but this is inefficient and indirect. Its priority is other roles. 2. Excess carbohydrate is converted to fat but this is inefficient and indirect. Its priority is glycogen stores. 3. Excess fat is efficiently converted to fat. B. The transition from feasting to fasting draws on reserves. C. Fasting—Inadequate Energy 1. Glucose is needed for the brain and nerve cells. 2. Protein meets glucose needs through amino acids that provide pyruvate. 3. The shift to ketosis occurs when the brain becomes fueled by ketone bodies. a. Ketones are produced when glucose is not available. 4. Ketosis causes a suppression of the appetite. 5. Hormones slow the metabolism. 6. Symptoms of Starvation: a. Muscle wasting. b. Decreased heart rate, respiratory rate, metabolic rate, and body temperature. c. Impaired vision. d. Organ failure. e. Decreased immunity. f. Depression, anxiety, and food-related dreams. D. Low-Carbohydrate Diets 1. Result in changes in metabolism similar to what occurs during fasting. 2. Ketones will be present in the urine when glycogen depletion has occurred. 3. When a dieter returns to a well-balanced diet, the body will retain depleted nutrients.

IV. Highlight: Alcohol (ethyl alcohol, ethanol) and Nutrition The metabolism of alcohol is handled differently in the body. Alcohol interferes with metabolism and impairs health and nutrition. There are potential health benefits to consuming moderate amounts of alcohol.

A. Alcohol in Beverages 1. Beer, wine, and distilled liquor (hard liquor) 2. Alcohol behaves like a drug, therefore altering body functions. 3. Moderation of drinks a. 5 ounces of wine b. 10 ounces of wine cooler c. 12 ounces of beer d. 1 ½ ounces distilled liquor (80 proof) B. Alcohol in the Body 1. Quickly absorbed. 2. Carbohydrates decrease the absorption of alcohol. 3. Alcohol dehydrogenase breaks down alcohol in the stomach. 4. Women absorb more alcohol then men. C. Alcohol Arrives in the Liver 1. Accumulation of fatty acids. 2. Alcohol dehydrogenase breaks down alcohol to acetaldehyde. 3. Alcohol abuse has damaging effects. 4. Coenzyme NAD. D. Alcohol Disrupts the Liver 1. Development of a fatty liver is the first stage of liver deterioration. 2. Fibrosis is the second stage. 3. Cirrhosis is the most advanced stage of liver deterioration. 4. Microsomal ethanol-oxidizing system (MEOS) metabolizes alcohol and drugs. E. Alcohol Arrives in the Brain 1. Alcohol acts as a narcotic, anesthetizes pain 2. Alcohol suppresses antidiuretic hormone (ADH), resulting in the loss of body water. F. Alcohol and Malnutrition 1. Heavy drinkers may have inadequate food intake. 2. Impaired nutrient metabolism will result from chronic alcohol abuse. 3. Vitamin B6, folate, thiamin deficiencies 4. Wernicke-Korsakoff syndrome is seen in chronic alcoholism. G. Alcohol’s Short-Term Effects 1. Accidents, fatalities, and breaking the law 2. Binge drinking or heavy drinking can result in death. H. Alcohol’s Long-Term Effects 1. Abuse during pregnancy. 2. Third leading cause of preventable death. 3. Health Effects of Heavy Alcohol Consumption a. Arthritis b. Cancer c. Fetal alcohol syndrome d. Heart disease e. Hyperglycemia f. Hypoglycemia g. Infertility h. Kidney disease i. Liver disease j. Malnutrition k. Nervous disorders l. Obesity m. Psychological disturbances I. Personal Strategies 1. Serve and consume nonalcoholic beverages. 2. Drink slowly and consume alcohol moderately. 3. Do not drive.

Case Study

Steve Quintana is a 52-year-old Hispanic male with a family history of alcoholism. He is 6 feet 1 inch tall and weighs 238 pounds, with much of his excess weight around his middle. He considers himself a social drinker although he has been arrested for driving under the influence of alcohol twice in the past five years. He recently has been diagnosed with diabetes and takes an oral medication to control his blood glucose. He also has high cholesterol and has recently started on a lipid-lowering medication. Recent tests have revealed Steve has fatty liver, which he feels is a result of his eating too much fat in his diet. He also reports having occasional low blood glucose (hypoglycemia) and feeling shaky and dizzy. 1. From information in this chapter, explain to Steve how his alcohol intake may be contributing to fatty liver. 2. What might explain the low blood sugar reactions Steve has been having? 3. Describe how the MEOS system described in Highlight 7 might affect the efficacy of the medications Steve takes. 4. What specific nutrient deficiencies is Steve at risk for due to excessive alcohol use? 5. Give Steve at least 3 health-related reasons to encourage him to seek help in abstaining from alcohol. 6. List at least 3 practical tips you would give to people who only drink alcohol occasionally and who want to stay within current recommendations for health and safety.

Answer Key 1. Alcohol is broken down in the liver in preference over fatty acids, which then accumulate. Alcohol also permanently changes the structure of liver cells, which impairs the liver’s ability to metabolize fats and can lead to fatty liver. 2. Fatty liver disrupts gluconeogenesis—making glucose from protein. Combined with his diabetes medication, this could cause low blood sugar. 3. Alcohol competes with drugs that use the MEOS system for metabolism. This may initially slow down the breakdown of these medications and cause them to build up in the blood. Later—when they are metabolized— the effects may be amplified with potentially fatal effects. If Steve stops drinking, the MEOS (which increases in efficiency in response to heavy alcohol use) may metabolize the drugs too quickly, possibly reducing efficacy.

4. B-vitamins, especially folate, thiamin, B12; vitamin D, vitamin A; protein. 5. Fat accumulation in the liver can be seen just one night after heavy drinking; damage to the liver from alcohol impairs bile production and release, which diminishes the body’s ability to digest fatty foods; vitamin D production is compromised. Fatty liver is reversible with abstinence from alcohol. If a person continues to drink, however, the liver deteriorates to fibrosis and then to cirrhosis, which is the least reversible form of liver disease. Alcohol also interferes with protein metabolism, which can affect immune function and deplete body protein stores that cannot be restored with diet alone. Abstinence is required. 6. Limit alcohol intake to no more than 1 (women) or 2 (men) drinks a day; do not drink on an empty stomach; drink a glass of water before each alcoholic drink; drink an extra 1 or 2 glasses of water before going to bed after drinking; drink no more than 1 drink per hour; do not drive if you have been drinking alcohol.

Enhancing Understanding of Metabolism

To explain human metabolism, an analogy based on the automobile can be offered. The oxidation of gasoline produces heat and energy (measured in miles per gallon) and carbon dioxide and water are waste products. Nutrients and gasoline are both fuels that are oxidized in the presence of oxygen to produce energy, carbon dioxide, and water. Consider a car having a manual transmission with only two gears: first and high. First gear is beneficial for rapid acceleration. If you do not shift out of first gear, the car will no longer accelerate, and it will use gasoline very inefficiently. You must shift into high gear to keep the car running efficiently at a higher speed. Human beings obtain energy from two analogous processes: glycolysis and the TCA cycle. Anaerobic glycolysis serves the need for quick energy to accomplish an intense activity for a short duration of time. For endurance activities, additional energy must be obtained from the TCA cycle. Explain that the choice of activity determines the proportion of fat and glucose burned during the activity. Energy Measure of Advantage Disadvantage Obtained Energy Car First gear Miles/gallon Quick acceleration Can only be used for a few seconds of acceleration Human Glycolysis ATP Quick, intense muscle Can only be used for a few beings anaerobic activity seconds as lactic acid is produced Car High gear Miles/gallon Used to sustain Depends on rate of oxygen desired velocity over delivery to fuel source; maximum amount of better tuned engines achieve time maximum miles/gallon Human TCA cycle ATP Used to sustain Depends on rate of oxygen beings aerobic desired amount of delivery to fuel source; muscle activity over better conditioning improves maximum amount of rate of oxygen delivery time

Critical Thinking Questions

1. Describe the following: catabolism, anabolism, coupled reactions, enzyme/coenzyme, photosynthesis, and cofactor.

Answer: Catabolism: This is the breakdown of energy-yielding compounds to provide energy for the body. For instance, the body can break down fat or it can use its own muscle tissue to provide energy to the body in times of starvation. Anabolism: This is the building of compounds, such as glycogen and proteins. Anabolic reactions require energy. Coupled Reactions: These are pairs of chemical reactions that assist one another. Energy released from one reaction can be used by the next reaction to complete the pair of reactions that would not exist independently. Enzyme/Coenzyme: An enzyme is a protein that “catalyzes” or facilitates a chemical reaction. A coenzyme works with an enzyme and is an organic molecule. Many B vitamins are part of coenzyme structures. Photosynthesis: The process carried out in plants that allows them to utilize the sun’s energy to make carbohydrates from carbon dioxide and water. In turn, by eating these plants, humans are also afforded energy. Cofactor: These organic and inorganic substances also help to facilitate the work of enzymes. They include both vitamins and minerals.

2. Discuss how the basic units of carbohydrate, protein, and lipid are utilized in energy pathways to produce energy. What are the differences and similarities? Answer: Carbohydrates, fats, and proteins all enter energy-producing pathways, but their fates do differ slightly, depending on their role and chemical composition. For example, while carbohydrates and fats are energy-yielding compounds, amino acids are really precursors to proteins and only a small percentage of their dietary consumption will be used for energy. Carbohydrates: Carbohydrates yield energy through a series of reactions beginning with glycolysis. Here a six-carbon glucose molecule is broken down into two three-carbon molecules that are converted to pyruvate. Anaerobically, pyruvate can be converted to lactate, allowing for a small amount of energy under anaerobic conditions, or the pyruvate can be broken down to acetyl-CoA under aerobic conditions in the TCA cycle. Conditions that allow pyruvate to move on through the TCA cycle into the electron transport chain will optimize the energy released from the initial glucose molecule Lipids: Triglycerides compounds are composed of two components, glycerol and fatty acids. Glycerol is a three-carbon compound and, as such, is able to enter glycolysis, either for gluconeogensis or for glycolysis (break down of glucose). From there, glycerol is broken down to pryuvate and continues on into the TCA cycle, producing energy via the electron transport system. Because there is only one glycerol unit for every three fatty acids, the number of glycerol compounds entering glycolysis is significantly less. Given that fatty acids are split into two-carbon compounds, they cannot enter the energy system until the point of acetyl-CoA. It is important to remember that because fatty acids enter at the point of acetyl-CoA, they are not capable of producing glucose. What is important to note here is that lipids do supply a source of energy from two different vantage points. While they enter the energy system at a different point from that of carbohydrates, there are some points in common. Secondarily, glycerol functions far differently than do the fatty acids. While glycerol can produce some glucose, its capability is limited given its scarcity relative to fatty acids. Amino Acids: The amino acids that make up proteins are very capable characters. They are able to enter the energy pathway at several points. However, prior to serving in any capacity in the energy pathways, they must be deaminated, which is the process in which their amine group is removed, thus removing the ammonia-producing unit. Amino acids can serve as a compound to make glucose through glycolysis and in the TCA cycle. Amino acids (non- essential) are distinguished by their ability to make glucose or ketones. Glucogenic amino acids enter glycolysis at the level of pyruvate as three-carbon compounds. They can be used to make pyruvate and then be used in gluconeogenesis to make glucose. Ketogenic amino acids are used to make acetyl-CoA. Other glucogenic amino acids can enter the TCA cycle as four-carbon compounds and serve as an energy source or be stored as fat. Amino acids are capable of producing glucose or ketones (in the absence of glucose) in the event of need for the body. The amino acid’s points of entry into the energy system are several and this demonstrates its vital purpose to our bodies. It must be remembered that the primary function of amino acids is tissue building and repair; therefore, this role in energy production is secondary to that of tissue maintenance.

3. If there were no external sources of energy available to the body, what would it do to produce energy? Discuss. Answer: If macronutrients are not available via ingested food, the body can rely on its stores of energy-yielding compounds to survive, often for an extended period. Glycogenolysis in the liver breaks down glycogen stores, and glucose is released into the blood; adipose tissues release fatty acids and glycerol into the blood as well. Because some cells prefer or can only metabolize glucose for energy, gluconeogenesis accelerates once liver glycogen is exhausted. The substrates for gluconeogenesis include glucogenic amino acids from degraded muscle tissues, so some muscle wasting will occur during a lengthy fast. This wasting is limited, however, by the acceleration of the formation of ketones—another energy-yielding compound that can be metabolized by certain cells, including those of the brain—from lipid and amino acid fragments. (The fatty acid fragments result from incomplete fat metabolism caused by the glucose shortage.)

4. In a state of starvation, several changes happen within our bodies. Talk about these metabolic changes and discuss the importance of interventions such as IV glucose and tube feedings for hospital patients that are severely sick and unable to eat.

Answer: In a state of starvation, the body continues to require energy to perform all of its functions. As noted many times throughout your text thus far, the brain is only able to utilize glucose or ketones, as is the majority of the nervous system. Even while an individual is asleep, the body continues to carry out thousands of metabolic reactions that require energy; thus, we calculate the basal metabolic rate, which is a significant part of any individual’s daily caloric requirements, for each client. Therefore, nutrients are needed for the body to function while sleeping. Added to that, a patient in a hospital setting has a body that is trying to heal from a trauma or disease. It must also be kept in mind that a hospital setting adds its own set of stress factors, environmentally, physically, etc. For the most part, hospital patients require added nutrients to heal and protect their bodies from the many hospital stress factors. Supplemental nutrients via an IV, tube feedings, etc. have been shown to decrease hospital stays for surgical patients. Something as simple as an IV with dextrose will provide the patient with added glucose for brain and nervous system function. While the calories are minimal, at best, it helps to prevent the patient from breaking down their own body tissues (ketosis) to support brain function, etc. The hydration is also important, particularly in the very young and the very old. Patients with longer stays should have recommended tube feedings or parentrel feedings to support the body functions for the increased periods of time. Such feedings can provide needed vitamins and minerals that may be easily lost in critical illness. Careful attention to patient hydration and supplemental feedings can save the patient their life as well as costly hospital stays. Nutrition can help to prevent skin breakdown, reverse dehydration, improve healing time, and brighten the overall outlook of the patient.

5. Using information regarding the pathways (biochemistry), discuss why dietary plans that only stress one or a couple of food groups are unhealthy physiologically.

Answer: After reading this chapter, the student should be able to see the importance of not only all the macronutrient groups but also the vitamins and minerals that assist as cofactors in many metabolic reactions. All of the food groups work together to ensure that our bodies are properly nourished. As noted, carbohydrates provide the body with an importance source of energy: glucose. Most particularly, the brain and nervous system benefit from this glucose, but the entire body benefits from the fiber, vitamins, and minerals received when an individual selects whole- grain carbohydrates. Selecting a diet that is void in carbohydrates forces the body to use proteins as an energy source and can deny the body vital amino acids for use in tissue building and repair under traumatic or stressful situations. This differential function between carbohydrates and protein is important to educate clients/patients about when providing nutrition counseling. Proteins are made up of the important building blocks called amino acids. Some of these are essential, meaning that they cannot be made by the body, and many are non-essential because the body can make them on its own. Selecting a diet with a variety of protein sources provides for the essential amino acids and ensures that the body has the building blocks it needs for tissue building, repair, etc. Production of glucose should be considered a secondary function for amino acids. While many individuals love foods drenched in butter, etc., dietary lipids need not be so abundant. Yet lipids are vital to a healthy body for production of steroid hormones and cell membranes, just to name a few important roles for lipids. In addition, a small amount of fat within the body is necessary to protect vital organs and to provide insulation from the cold. That being said, no more than two to three tablespoons a day of added lipid is necessary in our diets. As noted, glycerol can provide a limited source of glucose when necessary and fatty acids are broken down to acetyl-CoA as required for energy production. Otherwise, excess fatty acid consumption is easily converted to and stored as fat in the body. Without all of these macronutrients working together, our bodies would require one (such as proteins) to replace the function of another (such as carbohydrates). In these events, not only are their “normal” jobs disturbed but the other nutrients, such as vitamins and/or minerals, that may accompany a food group are also denied to the body. It is not the food group itself that causes an individual weight problems; it is the quantity of the food group that generally becomes the issue.