8 Metabolism and Nutrition

Transcription

1 154 Chapter 8 Metabolism and Nutrition Overview of Metabolism -Definition -Metabolism is a collective term that is used to refer to all of the chemical reactions that occur throughout the body. -Phases -There are 2 phases of metabolism: 1. catabolism -the breakdown of a polymer into its monomers or even smaller components -Examples: the breakdown of a protein into amino acids the breakdown of glucose into CO2 and H2O -Catabolism starts via the process of digestion in the lumen of the GI tract and is completed inside of the cells of the body. -Catabolic processes release energy (ATP and heat); the ATP is then used to power anabolic reactions. 2. anabolism -the synthesis of a polymer from several monomers -Examples: the synthesis of a triglyceride from 3 fatty acids and 1 glycerol molecule the synthesis of a protein from amino acids -Anabolic reactions occur within cells. -In addition, anabolic reactions require energy, which is released as ATP is hydrolyzed. -As mentioned earlier, this ATP is supplied by catabolic reactions. -Cells require anabolic reactions to grow, to repair themselves, and to produce secretory substances such as hormones, neurotransmitters, mucus, etc.

2 155 The Catabolism of Different Types of Nutrients glucose -If sufficient O2 is present (aerobic conditions), most cells catabolize glucose for energy via a process known as cellular respiration (Figure 8.1, Derrickson): glucose + O2 CO2 + H2O + 32 ATP -Figure 8.2 (Derrickson) summarizes the number of ATP produced per molecule of glucose catabolized via cellular respiration. -If O2 is absent or in low concentration in the cell (anaerobic conditions), glucose can still be catabolized, but only a small amount of energy is produced: glucose lactic acid + 2 ATP fatty acids -Most cells also contain enzymes that catabolize fatty acids for energy via cellular respiration (Figure 8.3, Derrickson): fatty acid + O2 CO2 + H2O + ATP (variable amounts) amino acids -In addition, hepatocytes (liver cells) contain enzymes that can catabolize amino acids for energy via cellular respiration (Figure 8.3, Derrickson): amino acid + O2 CO2 + H2O + ATP (variable amounts)

3 156 -The breakdown of an amino acid for energy involves the following steps: The amino acid is deaminated, which means that the amino group (NH2) is removed. The amino group is converted to ammonia (NH3). The rest of the amino acid is then converted into a keto acid, which is an intermediate organic compound. Most of the ammonia molecules produced from the deamination of amino acids are subsequently converted into urea. However, some of the ammonia molecules may not undergo this conversion reaction and, therefore, remain as ammonia. The keto acid is subsequently broken down into CO2, H2O, and ATP. The urea and any unconverted ammonia are then released from the liver into the blood. The kidney filters the blood of the urea and ammonia and excretes these substances from the body via urine.

4 157 Metabolic States -Overview -The types of metabolic reactions that occur in your body depend on how long it has been since you have eaten a meal. -Consequently, metabolic reactions are organized into 2 functional states: 1. absorptive state -the period when ingested nutrients are entering the blood from the GI tract to provide energy for the body 2. postabsorptive state -the period when the GI tract lacks nutrients and energy is supplied by the breakdown of the body s own nutrient reserves -It takes about 4 hours to completely digest and absorb a typical meal. -If you eat 3 meals a day, then your body spends about 12 hours each day in the absorptive state. -Examples: 7:00 a.m. breakfast (absorptive state is from 7:00 a.m. to 11:00 a.m.) 1:00 p.m. lunch (absorptive state is from 1:00 p.m. to 5:00 p.m.) 7:00 p.m. dinner (absorptive state is from 7:00 p.m. to 11:00 p.m.) -The other 12 hours of the day are spent in the postabsorptive state: late morning ( 2 hours in the postabsorptive state) Example: 11:00 a.m. to 1:00 p.m. late afternoon ( 2 hours in the postabsorptive state) Example: 5:00 p.m. to 7:00 p.m. late night and early morning ( 8 hours in the postabsorptive state) Example: 11:00 p.m. to 7:00 a.m. The term breakfast means breaking the fast and is derived from the fact that your body undergoes a fast during the long postabsorptive state that occurs overnight. -Absorptive State -2 major events occur during the absorptive state (Figure 25.17, Tortora): 1. Some of the absorbed nutrients are utilized for the body s energy needs. a. glucose -During the absorptive state, most cells of the body produce ATP by catabolizing glucose via cellular respiration. -Hence, during the absorptive state, glucose is the body s main energy source. b. amino acids -Some of the absorbed amino acids are used to synthesize proteins like actin and myosin in skeletal muscle and albumins in the liver. -Other absorbed amino acids are catabolized for energy by hepatocytes.

5 158 c. lipids -During the absorptive state, most of the absorbed lipids (short chain fatty acids, long chain fatty acids, and monoglycerides) are not catabolized for energy. - Instead, they are sent to adipose tissue and stored as triglycerides (fat). 2. Any absorbed nutrients in excess of the body s energy needs are converted into nutrient reserves. a. glycogen -glucose polymer -Excess glucose is stored as glycogen in the liver and skeletal muscle. -Glycogenesis is the synthesis of glycogen. b. adipose tissue -consists of adipocytes that store triglycerides -As mentioned earlier, most of the absorbed lipids are sent directly to adipose tissue and then stored as triglycerides. In addition, excess amino acids and excess glucose can be converted to triglycerides in the liver and then shipped to adipose tissue for storage. -Hence, just because a particular type of food is fat-free does not mean that you can eat it in excess because it can still be converted to fat. -Lipogenesis is the synthesis of triglycerides. -Postabsorptive State -During the postabsorptive state, the GI tract is empty of nutrients, but the cells of the body still need energy. Thus, the body s own nutrient reserves are catabolized to obtain this energy. -The major goal of the postabsorptive state is to maintain a normal blood glucose concentration (70 to 110 mg/dl of blood). -Keeping the blood glucose concentration constant is vital to the survival of the brain. This is because of the fact that neurons can only catabolize glucose (and not fatty acids, amino acids, etc.) for energy during a normal postabsorptive state. If the blood glucose concentration falls below normal, brain function is compromised and a coma occurs.

6 159-2 major events occur during the postabsorptive state (Figure 25.18, Tortora): 1. The blood glucose concentration is maintained at a normal level due to the catabolism of the body s nutrient reserves. -There are several sources of glucose during the postabsorptive state: a. glycogenolysis -the catabolism of glycogen into glucose -takes place in the liver and skeletal muscle -Once glycogenolysis occurs in the liver, the glucose is released into the blood. -In skeletal muscle, the glucose that is formed from glycogenolysis is often catabolized for energy. If the skeletal muscle exists under anaerobic conditions, then the glucose is converted into lactic acid, which is released into the blood. The liver then takes up the lactic acid, converts it back to glucose, and then releases the glucose into the blood. b. lipolysis -the catabolism of triglycerides into glycerol and fatty acids -takes place in adipose tissue -After lipolysis occurs, the glycerol and fatty acids are released into the blood. The liver then takes up the glycerol, converts it to glucose, and then releases the glucose into the blood. c. protein catabolism -the breakdown of protein into amino acids -takes place in skeletal muscle -After protein catabolism occurs, the amino acids are released into the blood. The liver then takes up each amino acid, converts it to glucose, and then releases the glucose into the blood. -In a normal postabsorptive state, glycogen is the main nutrient reserve catabolized, while only small amounts of lipid and protein are broken down.

7 160 -Gluconeogenesis -the formation of new glucose from a noncarbohydrate source -Examples: the formation of glucose from lactic acid, glycerol, or amino acid 2. Most tissues undergo glucose sparing. -This means that most cells of the body switch to fatty acid catabolism as their main source of energy; this leaves more glucose in the blood for the brain. -The fatty acids used by the body cells originate from lipolysis in adipose tissue. Cells take up the fatty acids from the blood and then catabolize them for energy. -In addition, hepatocytes take up some of the fatty acids from the blood and convert them to highly acidic compounds called ketones (also called ketone bodies) and then releases the ketones into the blood. Examples of these ketones include acetone, acetoacetate, and β-hydroxybutyrate. Cells then take up the ketones and then catabolize them for energy. -Note that in a normal postabsorptive state, only a very small (trace) amount of ketones are present in the blood. -However, if the postabsorptive state becomes extended (such as during a prolonged fast or starvation, lipolysis increases, which causes ketone production to increase. -The Extended Postabsorptive State prolonged fasting -the postabsorptive state lasts for a few days starvation -the postabsorptive state last for weeks -During prolonged fasting or starvation, several events occur: Glycogen reserves have become depleted. Lipolysis and ketone production increase. Protein catabolism increases.

8 161 A typical person can live off of his or her own lipid and protein stores for about 2 months as long as adequate water is consumed. Brain metabolism changes, allowing neurons to catabolize ketones in addition to glucose for energy. -Hormonal Regulation of Metabolism -There are several hormones that regulate various types of metabolic reactions. 1. insulin -Secretion Stimulus -Insulin is secreted from the β cells of the pancreas in response to a high blood glucose concentration (Figure 8.4, Derrickson). -The importance of blood glucose regulation is described in Figure 8.5 (Derrickson). -Functions -Insulin is the major hormone of the absorptive state; it promotes the following functions: Insulin causes glucose uptake by cells. -This reduces the blood glucose concentration back down to normal, physiological levels. -Insulin achieves this goal by increasing the number of glucose transporters (GluTs) in the membranes of most cells (Figure 8.6, Derrickson). -Note that liver cells and neurons do not require insulin to take up glucose. Insulin causes glycogenesis in the liver and muscle. Insulin causes amino acid uptake and protein synthesis in skeletal muscle. Insulin causes fatty acid & glycerol uptake and lipogenesis. 2. glucagon -Secretion Stimulus -The α cells of the pancreas secrete glucagon in response to a low blood glucose concentration (Figure 8.7, Derrickson). -The importance of blood glucose regulation is described in Figure 8.5 (Derrickson). -Functions: -Glucagon is the major hormone of the postabsorptive state; it promotes the following functions, all of which cause an increase in the blood glucose concentration back up to normal, physiological levels. Glucagon causes glycogenolysis in liver and skeletal muscle (Figure 8.8, Derrickson)

9 162 Glucagon causes gluconeogenesis in liver. Glucagon causes lipolysis in adipose tissue. -The fatty acids released from adipose tissue are used by the body s cells for energy. -The glycerol released is converted into glucose in the liver via the process of gluconeogenesis. 3. cortisol -Secretion Stimulus -Cortisol is secreted by the adrenal gland in response to a stressful situation (physical or emotional trauma, infection, surgery, starvation, extreme hot or cold temperatures, fear, severe exercise, etc.) (Figure 8.9, Derrickson). -Functions -Cortisol is another hormone that promotes the reactions of the postabsorptive state when the body is experiencing a stressful situation. -Cortisol has several functions, all of which allow the body to deal with the stress that is at hand: Cortisol generates energy (ATP) that the body can use to handle a stressful situation. - Cortisol achieves this goal in the following ways: Cortisol acts on skeletal muscle to cause protein catabolism and then release of amino acids into the blood. Cortisol acts on adipose tissue to cause lipolysis and then release of fatty acids and glycerol into the blood. Cortisol acts on the liver and skeletal muscle to cause glycogenolysis and then release of glucose into the blood. Cortisol acts on the liver to cause gluconeogenesis and then release of the glucose into the blood. -Once the glucose, fatty acids, and amino acids are released into the blood, the cells of the body can then take up these nutrients and then break them down via cellular respiration to produce enough energy to handle the stressful situation. -Since cortisol increases the blood glucose levels, it is also called a glucocorticoid.

10 163 Cortisol reduces inflammation and other immune responses. -inflammation - occurs in response to any tissue damage caused by injury or any foreign microbes that invade the body -characterized by redness, pain, heat, and swelling -serves as a call to arms that attracts leukocytes (white blood cells) to the area to fight the invading pathogens. -Whenever a tissue is damaged, nearby mast cells (cells found in connective tissue) and basophils (a type of white blood cells) cause inflammation by releasing a substance called histamine. -Cortisol reduces inflammation by reducing the amount of histamine released from mast cells and basophils in the injured tissue. -In addition, cortisol reduces the ability of white blood cells to mount an immune response to pathogens in the inflammed area. -These anti-inflammatory and anti-immune responses of cortisol are probably designed to allow the person to handle the stressful situation without having to be sidetracked by pain and other symptoms that are associated with inflammation and immune reactions. -Since cortisol inhibits immunity, it is often administered as an immunosuppressive drug to a person who receives an organ transplant. 4. thyroid hormones -includes triiodothyronine (T3) and thyroxine (T4) -secreted by the thyroid gland -T3 is more potent than T4; in addition, once these thyroid hormones are released into the blood, most of the T4 is converted into T3. -Secretion Stimulus -T3 and T4 secretion is regulated by the hypothalamus. Whenever the blood concentration of T3 and T4 is low, the hypothalamus secretes thyrotropin releasing hormone (TRH), which causes the anterior pituitary to secrete thyroid stimulating hormone (TSH); TSH then acts on the thyroid gland to promote secretion of T3 and T4 (Figure 8.10, Derrickson). -Functions -Thyroid hormones (T3 and T4) have several functions: Thyroid hormones are vital to the maturation of the nervous system during fetal development and childhood. Thyroid hormones stimulate bone growth. -Thyroid hormones achieve this goal by stimulating osteoblasts.

11 164 Thyroid hormones increase the basal metabolic rate (BMR). -As we shall soon see, the basal metabolic rate is the amount of energy produced (i.e. released) in an individual who is awake, resting, and recumbent (lying down) as that person s cells catabolize food via cellular respiration over a given period of time. -Some of the energy produced is in the form of ATP, while the rest is in the form of heat. Recall the equation for cellular respiration: metabolic enzymes monomer + O2 CO2 + H2O + energy (ATP, heat) (glucose, fatty acid or amino acid) -Hence, an increase in the BMR as caused by thyroid hormones also increases the body temperature. -Thyroid hormones increase the BMR by activating genes that cause the production of various metabolic enzymes involved in cellular (cellular) respiration. -Note that thyroid hormone secretion increases when a person is in a cold climate; this helps the person to adapt and to stay warmer due to more body heat from the increased BMR. Food Guide Pyramid -Figure (Tortora) illustrates the Food Guide Pyramid (MyPlate). Calories -Definition -A calorie is a measure of how much energy is released when a particular type of food is catabolized via cellular respiration. 1 Calorie (Cal) = 1 kilocalorie (kcal) = 1000 calories -Most of the Calories in our food are derived from the catabolism of carbohydrates, proteins, and fats. The catabolism of 1g of carbohydrate yields about 4 Cal of energy. The catabolism of 1g of protein also yields about 4 Cal of energy. The catabolism of 1g of fat yields about 9 Cal of energy.

12 165 -Calculation of Calories in Food 1 slice of super supreme pizza from Pizza Hut nutritional information 27 g carbohydrate 14 g fat 12 g protein Calculate the number of Calories from carbohydrate in this slice of pizza. 27 g carbohydrate x 4 Cal = 108 Cal 1 g carbohydrate Calculate the number of Calories from fat in this slice of pizza. 14 g fat x 9 Cal = 126 Cal 1 g fat Calculate the number of Calories from protein in this slice of pizza. 12 g protein x 4 Cal = 48 Cal 1 g protein What is the total number of calories in this slice of pizza? 108 Cal Cal + 48 Cal = 282 Cal -Calorie Composition -Tables 25.6 and 25.7 (Tortora) list the caloric content of various foods and beverages. -The higher the caloric content of a particular food, the more energy that is released as it is catabolized. Examples: an apple vs. McDonald s Big Mac 1 apple = 80 Cal This means that 80 Cal is the amount of energy released as this apple is catabolized. 1 Big Mac = 541 Cal This means that 541 Cal is the amount of energy released as this Big Mac is catabolized. Suppose that you eat the apple OR the Big Mac. -Based on the caloric content of these foods, your body will have to work harder (via exercise, etc.) to release more energy in order to catabolize the Big Mac versus the apple.

13 166 Basal Metabolic Rate -The basal metabolic rate (BMR) is the amount of energy produced (i.e. released) in an individual who is awake, resting, and recumbent (lying down) as that person s cells catabolize food via cellular respiration over a given period of time. -An average man has a weight of about 70 kg (155 lbs) and a BMR of 1700 Cal/day. This means that in order to survive under resting conditions, a typical male must eat enough food each day to release about 1700 Cal via cellular respiration. -The energy released is used to power the essential activities such as breathing, thinking, active transport across cell membranes, etc. -BMR varies with gender, age, body weight, and hormones (especially thyroid hormones). -For men, the BMR = 1.0 Cal/kg of body weight/hour. Recall that kg means kilogram. -Hence, a man can calculate his BMR per day by using the following formula: BMR (for men) = body weight in kg x 1 Cal x 24 hours 1 kg of body weight/hour -For women, the BMR = 0.9 Cal/kg of body weight/hr. -Hence, a woman can calculate her BMR per day by using the following formula: BMR (for women) = body weight in kg x 0.9 Cal x 24 hours 1 kg of body weight/hour Recall that 1 kg = 2.2 lbs. Hence, to convert your weight in pounds to kilograms, divide your weight in pounds by 2.2 and then use the above formulas. -Realize that your burn more calories per day than your BMR because you typically do more than just rest and recline. -Recall that the BMR is measured when you are alert, resting, and recumbent (lying down). -Table 25.8 (Tortora) lists various muscular activities and the calories that they burn per hour. -Hence, the total metabolic rate (TMR) equals your BMR plus the amount of calories burned from activities that involve muscular work. TMR = BMR + (calories burned from activities involving muscular work)

14 167 -Therefore. If your daily caloric intake equals your total metabolic rate, then your weight remains the same. If your daily caloric intake is greater than your total metabolic rate, then you will gain weight. If your daily caloric intake is less than your total metabolic rate, then you will lose weight. -Note that as a person ages, skeletal muscles atrophy, which reduces the amount of activities that he or she can perform. -Therefore, the total metabolic rate decreases as a person becomes older, and there is typically a gain in weight if daily caloric intake is not reduced. -One final point that can be used during Calorie Counting: 1 lb = 3500 Cal Lipid Transport -Overview -Lipids are hydrophobic and do not dissolve well in blood. Recall that blood is hydrophilic due to the presence of water. -Thus, proteins typically must increase the solubility of lipids in blood by coating them, forming structures called lipoproteins. lipoprotein -consists of a lipid core surrounded by a protein coat -Types of Lipoproteins -Lipoproteins are classified based on their densities; there are 4 major types of lipoproteins, which are listed from lightest to heaviest: chylomicrons, VLDLs, LDLs, and HDLs (Figure 8.11, Derrickson).

15 chylomicron primarily consists of triglyceride molecules that are surrounded by a protein coat formed within absorptive cells of the small intestine function: carries absorbed triglycerides from the small intestine to adipose tissue for storage 2. very low-density lipoprotein (VLDL) primarily consists of triglyceride molecules that are surrounded by a protein coat formed in the liver function: transports triglycerides from the liver to adipose tissue for storage 3. low-density lipoprotein (LDL) primarily consists of cholesterol molecules that are surrounded by a protein coat formed in the liver function: transports cholesterol from the liver to body cells -The cells of the body use the cholesterol to help synthesize plasma membranes. Recall that the plasma membrane of a cell is a lipid bilayer that consists of phospholipids, cholesterol, and proteins.

16 169 -In addition, certain cells use cholesterol to synthesize steroid hormones. -Examples: Cells of the adrenal gland use cholesterol to synthesize cortisol, aldosterone, and the adrenal androgens. Cells of the ovaries use cholesterol to synthesize estrogen and progesterone. Cells of the testes use cholesterol to synthesize testosterone. called bad cholesterol because as it travels to body cells, if too much cholesterol is present then the excess cholesterol will ooze out of the LDL and form lipid plaques in the walls of blood vessels (arteriosclerosis). 4. high-density lipoprotein (HDL) initially resembles a deflated beach ball, consisting of a protein coat with an empty interior gradually adds more and more cholesterol to its interior by pulling off cholesterol that has been deposited on arterial walls formed in the liver function: absorbs unused cholesterol from the circulation and brings it to the liver -The liver then excretes the cholesterol into bile, which eventually becomes part of the feces; hence, bile is the major mechanism by which cholesterol is excreted from the body. called good cholesterol

17 170 -Cholesterol -Sources 1. diet -There are several types of foods that are high in cholesterol and, therefore, should be eaten in moderation: eggs, dairy products, beef, pork, shellfish (shrimp, etc.). -Cholesterol intake should be under 300 mg/day. 2. liver -The cholesterol produced by the liver is used to make bile salts, steroid hormones, and plasma membranes. -Blood Cholesterol Screening Procedure To find out your cholesterol level, a health care professional withdraws a sample of your blood after you have fasted overnight. The various lipoproteins are isolated from the plasma and their concentrations are then determined. The total blood cholesterol should be under 200 mg/dl of blood. Note that dl stands for deciliter, which is 0.1L or 100 ml of blood. The ideal LDL concentration: < 130 mg/dl of blood The ideal HDL concentration: > 40 mg/dl of blood. A person has an increased risk for coronary artery disease/ arteriosclerosis if one or more of the following apply: The total blood cholesterol concentration is higher than normal. The LDL concentration is higher than normal. The HDL concentration is lower than normal. -Therapy for High Blood Cholesterol regular exercise -Exercise increases the HDL concentration. changes in diet -Eating foods with less cholesterol will decrease the LDL concentration. drugs Some drugs increase cholesterol excretion into bile. Other drugs reduce cholesterol synthesis in the liver.

18 171 Clinical Applications and Disorders -Look up the following clinical applications and disorders in Tortora: 1. diabetes mellitus p ketosis p phenylketonuria p emotional eating p obesity p kwashiorkor p malnutrition p marasmus p thyroid gland disorders p Cushing s syndrome p Addison s disease p. 663

19 Figure 8.1 Cellular Respiration of Glucose 172

20 Figure 8.2 Summary of ATP Produced Per Molecule of Glucose Catabolized in Cellular Respiration 173

21 Figure 8.3 Entry of Glucose, Fatty Acids, and Amino Acids Into Cellular Respiration 174

22 175 Figure 8.4 Insulin ( ) High Blood Glucose Concentration ( ) Pancreas (β cells) Insulin glucose uptake by body cells glycogenesis in liver and muscle amino acid uptake and protein synthesis in muscle fatty acid, glyercol uptake and lipogenesis in adipocytes Note: (-) implies a negative feedback effect.

23 176 Figure 8.5 Blood Glucose Concentration Normal Blood Glucose Concentration 70 to 110 mg/dl Hypoglycemia deficiency of glucose in the blood may lead to convulsions, mental confusion, and coma Hyperglycemia an excess of glucose in the blood may lead to poor circulation, gangrene, cataracts, and retinal dysfunction/blindness

24 Figure 8.6 Role of Insulin in Promoting Glucose Uptake by Cells 177

25 178 Figure 8.7 Glucagon ( ) Low Blood Glucose Concentration ( ) Pancreas (α cells) Glucagon glycogenolysis in lipolysis in gluconeogenesis liver and muscle cells adipocytes in liver cells Note: (-) implies a negative feedback effect.

26 Figure 8.8 Role of Glucagon in Promoting Glycogenolysis in a Hepatocyte 179

27 180 Figure 8.9 Corticotropin Releasing Hormone (CRH), Adrenocorticotropic Hormone (ACTH), and Cortisol stressful situation (physical or emotional trauma, infection, surgery, starvation, extreme hot or cold temperatures, fear, severe exercise, etc.) Hypothalamus ( ) CRH Anterior Pituitary ( ) ACTH high blood cortisol concentration adrenal gland cortisol glycogenolysis in liver and muscle lipolysis in adipose tissue gluconeogenesis in liver Note: (-) implies a negative feedback effect. protein catabolism in skeletal muscle inflammation immune response

28 181 Figure 8.10 TRH, TSH, and Thyroid Hormones (T3 and T4) Low blood concentration of T3 and/or T4 Hypothalamus ( ) TRH Anterior Pituitary ( ) TSH high concentration of T3 and/or T4 in the blood thyroid gland thyroid hormones (T3 and T4) maturation of basal metabolic rate growth of bone nervous system Note: (-) implies a negative feedback effect.

29 Figure 8.11 Lipoprotein Function 182