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Saladin 5e Extended Outline Chapter 26 Nutrition and Metabolism I. Nutrition (pp. 1014–1025) A. Body weight is determined by the body’s energy balance. (p. 1014) 1. If intake exceeds output, weight is gained; if output exceeds intake, weight is lost. 2. Weight usually remains stable over many years’ time and seems to have a homeostatic set point. 3. In humans, the set point varies greatly, and body weight results from a combination of hereditary and environmental influences. 4. 30% to 50% of the variation in human weight appears due to heredity, and the rest to environmental factors such as eating and exercise. B. Appetite is controlled in the body by peptide hormones and regulator pathways that affect short-term and long-term appetite and body weight. (pp. 1014–1017) 1. Some hormones are termed gut–brain peptides because they act as chemical signals from the GI tract to the brain. 2. Three peptides work as short-term regulators of appetite over periods of minutes to hours. a. Ghrelin is secreted by parietal cells in the fundus of the stomach, especially when it is empty. i. It produces the sensation of hunger and stimulates the hypothalamus to secrete growth hormone–releasing hormone. ii. Within an hour after eating, ghrelin secretion ceases. b. Peptide YY (PYY) is secreted by enteroendocrine cells in the ileum and colon, which sense that food has arrived as it enters the stomach. i. PPY is secreted long before the chyme reaches the ileum, and in quantities proportion to calories consumed. ii. It is a member of a family of hormones related to neuropeptide Y (NPY). iii. The primary effect of PPY is to signal satiety and terminate eating. iv. It remains elevated well after a meal and acts as a ileal brake to prevent the stomach from emptying too quickly. c. Cholecystokinin (CCK) is secreted by enteroendocrine cells in the duodenum and jejunum. i. It stimulates bile and pancreatic enzymes. Saladin Outline Ch.26 Page 2 ii. It also stimulates the brain and sensory fibers of the vagus nerves, producing an appetite-suppressing effect. 3. Other peptides are involved in long-term regulation of appetite, metabolic rate, and body weight over week to years; two examples, leptin and insulin, work as “adiposity signals.” a. Leptin is secreted by adipocytes throughout the body, and its level is proportional to one’s fat stores. i. This is the brain’s primary way of knowing how much body fat we have. ii. Animals with a leptin deficiency or defect in leptin receptors exhibit hyperphagia and extreme obesity. iii. With few exceptions, obese humans are not leptin deficient and are not aided by leptin injections. iv. Obesity is linked to unresponsiveness to leptin—a receptor defect. v. Adipose tissue is increasingly seen as an important source of multiple hormones influencing energy balance. b. Insulin is secreted by the pancreatic beta cells and stimulates glucose and amino acid uptake and glycogen synthesis—but it also has receptors in the brain. i. On these receptors it functions like leptin as an index of the body’s fat stores. ii. It has a weaker effect than leptin. 4. The arcuate nucleus of the hypothalamus is important in appetite regulation. a. All five peptides described above had receptors in the arcuate nucleus in addition to other target cells in the body. b. The arcuate nucleus has two neural networks involved in hunger. i. One network secretes neuropeptide Y (NPY), a powerful appetite stimulant. ii. The other secretes melanocortin, which inhibits eating. iii. Ghrelin stimulates NPY secretion, whereas insulin, PPY, and leptin inhibit it. iv. Leptin also stimulates melanocortin secretion. (Fig. 26.1) v. Leptin inhibits secretion of appetite stimulants called endocannabinoids, which resemble tetrahydrocannabinol (THC) of marijuana. Insight 26.1 Obesity 5. In addition to the action of gut–brain peptides, hunger is also stimulated partly by gastric peristalsis. Saladin Outline Ch.26 Page 3 a. Mild hunger contractions begin soon after the stomach is emptied and increase over a few hours. b. Food intake is terminated not only by PPY and CCK, but also in ways similar to the way that water intake slakes thirst. i. Merely chewing and swallowing food briefly satisfies the appetite even if the food does not reach the stomach. ii. Inflating a balloon in the stomach also inhibits hunger in the same way a meal would. iii. Satiation is short lived in these situations, and lasting satiation depends on the absorption of nutrients. 6. Appetite involves not only how much but also what kind of food is consumed. a. In humans, different neurotransmitters seem to govern the appetite for different classes of nutrients. b. Norepinephrine stimulates appetite for carbohydrates, galanin for fatty food, and endorphins for protein. C. A calorie is defined as the amount of heat that will raise the temperature of 1 g of water 1°C; one thousand calories is a Calorie in dietetics and a kilocalorie (kcal) in biochemistry. (p. 1017) 1. In physiology, calories are a measure of the capacity to do biological work. 2. Nearly all dietary calories come from carbohydrates, proteins, and fats. a. Carbohydrates and proteins yield about 4 kcal/g when completely oxidized; fats yield about 9 kcal/g. b. Alcohol (7.1 kcal/g) and sugary foods can promote malnutrition by providing “empty calories”—energy without nutritional diversity. c. In sound nutrition, energy needs are met by complex foods that provide proteins, lipids, vitamins, and other nutrients. d. “Fuel” in nutrition discussions refers to a chemical oxidized solely or primarily to extract energy, usually to make ATP for other physiological processes. D. A nutrient is any ingested chemical that is used for growth, repair, or maintenance of the body. (p. 1017) 1. Nutrients fall into six major classes: water, carbohydrates, lipids, proteins, minerals, and vitamins. (Table 26.1) a. Macronutrients include water, carbohydrates, lipids, and proteins because relatively large quantities are needed. b. Micronutrients include minerals and vitamins because only small quantities are required. Saladin Outline Ch.26 Page 4 2. Recommended daily allowances (RDAs) of nutrients were first developed in 1943 by the National Research Council and National Academy of Sciences and have been revised several times since. a. An RDA is a liberal but safe estimate of the daily intake that would meet the nutritional needs of most healthy people. b. Consuming less than the RDA does not necessarily mean malnutrition, but the probability of malnutrition increases according to the amount of deficit and length of time. 3. Essential nutrients are those the body cannot synthesize and include minerals, most vitamins, eight of the amino acids, and one to three of the fatty acids. E. About 440 g of carbohydrates are present in the body of a well-nourished adult, most of which (325 g) is in the muscle as glycogen. (pp. 1018–1019) 1. Sugars function as a structural component of other molecules including nucleic acids, glycoproteins, glycolipids, ATP, and related nucleotides. 2. They can also be converted to amino acids and fats. 3. Most of the carbohydrate serves as fuel—an easily oxidized source of chemical energy. a. Some cells, such as neurons and erythrocytes, depend almost exclusively on carbohydrates as an energy source; hypoglycemia (low blood glucose) can cause nervous system disturbances felt as weakness or dizziness. b. Blood glucose concentration is carefully regulated mainly through the interplay of insulin and glucagon. i. These hormones regulate the balance between glycogen and free blood glucose. ii. It is important to consume enough carbohydrate to ensure adequate stores of glycogen for periods of exercise and fasting (including sleep). 4. Carbohydrate intake influences the metabolism of other nutrients. a. Fat is oxidized as fuel when glucose and glycogen levels are too low to meet energy needs; conversely, excess carbohydrate is converted to fat. b. Excessive reduction of carbohydrate intake in an effort to lose fat may lead to incomplete fat oxidation, formation of ketone bodies, and metabolic acidosis. 5. Carbohydrates are required in greater amounts than any other nutrient, with an RDA of 125 to 175 g. a. The brain alone consumes about 120 g of glucose per day. b. Most Americans get 40% to 50% of their calories from carbohydrates, but highly active people should get up to 60%. Saladin Outline Ch.26 Page 5 c. Carbohydrate consumption in the United State has become excessive over the last century because of fondness for sweets, increased use of sugar in processed foods, and reduced physical activity. i. In the last century, average consumption of sugar has increased almost 27-fold, from 4 lb per year to 106 lb per year. d. The three principle forms of dietary carbohydrates are monosaccharides, disaccharides, and polysaccharides (complex carbohydrates). i. The only nutritionally significant polysaccharide is starch. ii. Only trivial amounts of glycogen are present in cooked meats. iii. Cellulose is not considered a nutrient because it is indigestible. e. The three major dietary disaccharides are sucrose, lactose, and maltose. f. The monosaccharides—glucose, galactose, and fructose—arise mainly from digestion of starch and disaccharides. i. Ultimately all carbohydrate digestion generates glucose. ii. Outside the hepatic portal system, glucose is the only monosaccharide present in the blood in significant quantity, and so it is known as blood sugar. iii. Normal blood sugar is normally maintained at 70–110 mg/dL in venous blood. g. Ideally, most carbohydrate intake should be in the form of complex carbohydrates, but a typical American now obtains only 50% of his or her carbohydrates from starch and the other 50% from sucrose and corn syrup. Insight 26.2 Evolution of the Sweet Tooth 6. Nearly all dietary carbohydrates come from plants. a. Sucrose is refined from sugarcane and sugar beets. b. Fructose is present in fruits and corn syrup. c. Maltose is present in some foods such as germinating cereal grains. d. Lactose is the most abundant solute in cow’s milk (about 4.6% lactose by weight). 7. Dietary fiber refers to all fibrous materials of plant and animal origin that resist digestion. a. Fiber is an essential component of the diet, with an RDA of about 30 g. b. Water-soluble fiber includes pectin and certain other carbohydrates found in oats, beans, peas, carrots, brown rice, and fruits. i. It reduces blood cholesterol and low-density lipoprotein (LDL). c. Water-insoluble fiber includes cellulose, hemicellulose, and lignin. Saladin Outline Ch.26 Page 6 i. It apparently has no effect on cholesterol or LDL levels, but softens the stool and increases its bulk by 40% to 100%, reducing the risk of constipation and diverticulitis. d. Dietary fiber has no clear effect on the incidence of colorectal cancer, and excessive fiber can interfere with the absorption of iron, calcium, magnesium, phosphorus, and some trace elements. F. Lipids make up 15% and 25% of the reference male and female body, respectively, by weight. (pp. 1019–1021) 1. Fat accounts for most of the body’s stored energy, and small amounts of phospholipid, cholesterol, and other lipids also play vital structural and physiological roles. a. A well-nourished adult meets 80% to 90% of his or her resting energy needs from fat. b. Fat is superior to carbohydrate for energy storage for two reasons. i. Carbohydrates are hydrophilic, absorb water, and expand to occupy space, while fats are hydrophobic and is more compact. ii. Fat is less oxidized than carbohydrate to begin with and contains over twice as much energy (9 kcal/g compared with 4 kcal/g). c. Fat has glucose-sparing and protein-sparing effects—as long as enough fat is available, protein is not catabolized for fuel and glucose is spared for neurons. d. Vitamins A, D, E, and K are fat soluble, so they depend on dietary fat for their absorption by the intestine; vitamin deficiency may result if less than 20 g of fat per day is eaten. e. Phospholipids and cholesterol are major structural components of membranes, and cholesterol is an important precursor of hormones, bile acids, and vitamin D. f. Adipose tissue has important protective and insulating functions. 2. Fat should account for no more than 30% of the caloric intake, and no more than 10% should be saturated fat. a. Cholesterol intake should not exceed 300 mg/day. b. One egg yolk has 240 mg/day. c. A typical American consumes 40% to 50% of calories from fat and twice as much cholesterol as recommended. d. Essential fatty acids are those that cannot be synthesized by the body and include linoleic acid and possibly linolenic and arachidonic acids. 3. In terms of sources, saturated fats are predominantly of animal origin but are also present in some plant products such a coconut and palm oils. Saladin Outline Ch.26 Page 7 a. Processed foods such as hydrogenated oils and vegetable shortening are also high in saturated fats. b. Unsaturated fats are present in nuts, seeds, and most vegetable oils. c. Excessive consumption of saturated and unsaturated fats is a risk factor for diabetes mellitus, cardiovascular disease, and breast and colon cancer. d. The richest source of cholesterol is egg yolks, but it is also prevalent in milk products, shellfish, organ meats, and other mammalian meat. 4. Serum lipoproteins transport hydrophobic cholesterol and triglycerides through the aqueous blood plasma. a. A lipoprotein is a tiny droplet complex consisting of a core of cholesterol and triglycerides with a protein and phospholipid coating. i. The coating enables the lipids to remain suspended in the blood and also serves as a recognition marker for cells that absorb them. ii. The complexes are often referred to as serum lipoproteins because their concentrations are expressed in terms of a volume of blood serum, not whole blood. b. Lipoproteins are classified into four major categories by their density: chylomicrons, very-low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs); they also vary with size— smaller lipoproteins are generally more dense because of the increased proportion of protein to lipid. (Fig. 26.2a) c. Chylomicrons (75–1,200 nm in diameter) form in the absorptive cells of the small intestine and pass into the lymphatic system. i. The endothelial cells of the blood capillaries have a surface enzyme, lipoprotein lipase, that hydrolyzes chylomicron triglycerides so they can pass through the capillary walls into adipocytes. ii. Some free fatty acids (FFAs) remain in the blood plasma bound to albumin. iii. The remainder of a chylomicron after the triglycerides are removed, called a chylomicron remnant, is degraded by the liver. d. VLDLs (30–80 nm) transport lipids to adipose tissue for storage and then become LDLs when their triglycerides are removed. e. LDLs (18–25 nm) contain mostly cholesterol and are absorbed by cells that need cholesterol by receptor-mediated endocytosis. f. HDLs (5–12 nm) are synthesized in the liver as empty, collapsed protein shells that travel in the blood and picks up cholesterol and phospholipids from other organs. Saladin Outline Ch.26 Page 8 i. When the HDL circulates through the liver, the liver removes the cholesterol and eliminates it. ii. HDLs are therefore a vehicle for removing excess cholesterol from the body. 5. The desirable level of total plasma cholesterol is 200 mg/dL or less; 200–239 mg/dL is considered borderline high, and over 240 mg/dL is considered pathological. 6. Most of the body’s cholesterol is synthesize internally rather than coming from the diet, and the body compensates for variations in dietary intake. a. Lowering cholesterol intake reduces the serum cholesterol by no more than 5%; however, certain saturated fatty acids raise serum cholesterol. i. Palmitic acid blocks the uptake of cholesterol by tissues, while stearic acid does not. ii. A moderate reduction of saturated fatty acid intake can lower blood cholesterol by 15% to 20%. b. Vigorous exercise also lowers blood cholesterol levels through a roundabout mechanism. i. Exercise reduces the sensitivity of the right atrium to blood pressure, so less atrial natriuretic peptide is secreted. ii. The kidneys excrete less sodium and water, and the blood volume rises. iii. This dilutes the lipoproteins in the blood, and the adipocytes compensate by producing more lipoprotein lipase. iv. The adipocytes therefore consume more blood triglycerides, shrinking the VLDL particles, which shed some cholesterol in the process. v. HDLs pick up the free cholesterol for removal by the liver. c. A high LDL concentration in the blood is a warning sign because it signifies a high rate of cholesterol deposition in the arteries. i. LDLs are elevated not only by saturated fats but also by tobacco, coffee, and stress. d. A high proportion of HDL is beneficial because it indicates that cholesterol is being removed from the arteries. e. It is desirable to increase the ratio of HDL to LDL through a diet low in calories and saturated fats and through regular aerobic exercise. G. Proteins constitute about 12% to 15% of the body’s mass; 65% of it is in the skeletal muscles. 1. Proteins have a vast number of roles in the body, from muscle contraction to transport to structure; no other class of biomolecules has such a diversity of functions. Saladin Outline Ch.26 Page 9 2. The RDA of protein is 44 to 60 g depending on age and sex. a. Multiplying your weight in pounds by 0.37 (or weight in kilograms by 0.8) gives and estimate of your RDA. b. A higher intake is recommended, however, under conditions of stress, infection, injury, and pregnancy. i. Infants and children require more protein than adults relative to body weight. ii. Excessive protein intake can overload the kidneys and cause renal damage. c. Total protein intake is not the only significant measure of dietary adequacy; the nutritional value of the protein must supply the right amino acids in the correct proportions. i. Eight amino acids are termed essential amino acids because the human body cannot synthesize them (leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine). ii. In addition, 2 amino acids can only be synthesized from essential amino acids (cysteine from methionine and tyrosine from phenylalanine). iii. The other 10 (9 in infants) are called inessential amino acids because the body can synthesize them independently of diet. d. Cells do not store surplus amino acids; when a protein is to be synthesized, all amino acids necessary must be present at once. i. High-quality complete proteins are those that provide all essential amino acids in the necessary proportions for human tissues. ii. Lower-quality incomplete proteins lack one or more essential amino acids—cereals are low in lysine, and legumes are low in methionine. e. Protein quality is also determined by net protein utilization—the percentage of amino acids in a protein that the human body uses. i. 70% to 90% of animal protein is utilized, compared to 40% to 70% of plant protein. ii. Therefore a larger serving of plant foods than animal foods is needed to provide human protein requirements. iii. 14 ounces of rice and beans provides as much usable protein as 4 ounces of hamburger. iv. Reducing meat intake and increasing plant intake does have advantages in terms of vitamins, minerals, fiber, and lower intake of saturated fat. Saladin Outline Ch.26 Page 10 v. Less land use is necessary to produce crops for food than to produce animals for food. 3. In terms of dietary sources, animal proteins from meat, eggs, and dairy products are complete protein, whereas plant proteins are incomplete. a. Combining of plant foods, such as rice with beans, can provide a complete source of protein. b. About two-thirds of the world’s population receives adequate nutrition from diets with very little meat. 4. Proteins are the chief dietary source of nitrogen. a. Nitrogen balance is a state in which the rate of nitrogen ingestion equals the rate of excretion (as nitrogenous wastes). b. Children exhibit a state of positive nitrogen balance because they ingest more than they excrete while growing. c. Pregnant women and athletes in resistance training also show positive nitrogen balance. d. When excretion exceeds ingestion, a state of negative nitrogen balance occurs, indicating the body proteins are being broken down and used as fuel. i. Negative nitrogen balance tends to be associated with muscle atrophy. ii. Negative balance may occur if carbohydrate and fat intake are insufficient to meet the need for energy. iii. Carbohydrates and fats are said to have a protein-sparing effect because they prevent protein catabolism when present for energy needs. e. Nitrogen balance is affected by some hormones, such as growth hormone and sex steroids (positive nitrogen balance) and glucocorticoids (negative nitrogen balance). H. Minerals are inorganic elements that plants extract from soil or water and introduce into the food web; vitamins are small dietary organic compounds that are necessary to metabolism. (pp. 1022–1025) 1. Neither minerals nor vitamins are used as fuel, but they are essential in relatively small quantities to our ability to use other nutrients. 2. Minerals are about 4% of the body mass, with ¾ being calcium and phosphorus in the bones and teeth. a. Phosphorus is also a key component of ATP, cAMP, GTP, and creatine phosphate and is the basis of the phosphate buffer system. b. Calcium, iron, magnesium, and manganese function as cofactors for enzymes. c. Iron is also essential to hemoglobin and myoglobin. Saladin Outline Ch.26 Page 11 d. Chlorine is a component of stomach acid (HCl). e. Many mineral salts function as electrolytes and govern action of nerve and muscle cells as well as regulate content and distribution of water and maintain blood volume. f. The best sources of minerals are vegetables, legumes, milk, eggs, fish, shellfish, and some other meats. (Table 26.2) g. Sodium chloride has been both a prized commodity and a curse. i. Animal tissues contain relatively large amounts of salt, but plants are relatively poor in it; herbivores must supplement their diet by ingesting salt from the soil. ii. As agriculture developed, humans became dependent on supplemental salt. iii. The American diet of today, however, contains excess salt, both added at the table and in processed foods. iv. Excess salt intake is especially dangerous in cases of hypertension. 2. Vitamins were originally named with letters in the order of their discovery but also have chemically descriptive names. a. Most vitamins must be obtained from the diet, but the body can synthesize some of them from precursors called provitamins. (Table 26.3) b. Vitamins are classified as water-soluble or fat-soluble. c. Water-soluble vitamins are absorbed with water from the small intestine, dissolve freely in body fluids, and are quickly excreted. i. They cannot be stored and seldom accumulate to excess. ii. Water-soluble vitamins are ascorbic acid (vitamin C) and the B vitamins. iii. Ascorbic acid promotes hemoglobin synthesis, collagen synthesis, and sound connective tissue structure and is also an antioxidant. iv. B vitamins function as coenzymes or parts of coenzymes, assisting in electron transfer. d. Fat-soluble vitamins are incorporated into lipid micelles in the small intestine and are absorbed with dietary lipids. i. Vitamin A is a component of the visual pigments and promotes proteoglycan synthesis and epithelial maintenance. ii. Vitamin D promotes calcium absorption and bone mineralization. iii. Vitamin K is essential to prothrombin synthesis and blood clotting. iv. Vitamins A and E are antioxidants, like vitamin C. Saladin Outline Ch.26 Page 12 e. Diseases may result from vitamin deficiencies and also from hypervitaminosis (vitamin excess). i. A deficiency of vitamin A can result in night blindness, dry skin and hair, a dry conjunctiva and cloudy cornea, and increased incidence of infection. ii. An excess of vitamin A may cause anorexia, nausea and vomiting, headache, pain and fragility of bones, hair loss, and enlarged liver and spleen, and may also cause birth defects. iii. Hypervitaminosis is also thought to be possible with vitamins B 6, C, D, and E. f. Megadoses of vitamins, doses 10 to 1,000 times the RDA, do not seem to be helpful except when used to correct a vitamin deficiency; megadoses of fatsoluble vitamins can be especially harmful. II. Carbohydrate Metabolism (pp. 1025–1033) A. Most dietary carbohydrate is burned as fuel within a few hours; galactose and fructose are quickly converted to glucose, and all oxidative consumption is essentially glucose catabolism that produces ATP. (p. 1025) 1. C6H12O6 + 6O2 6CO2 + 6H2O B. Glucose catabolism breaks down glucose in a series of enzyme-controlled steps, and as much energy as possible is transferred to ATP. (pp. 1025–1026) 1. There are three major pathways of glucose catabolism. (Figs. 26.3–26.6) a. Glycolysis splits a glucose molecule into two molecules of pyruvic acid. b. Anaerobic fermentation, which reduces pyruvic acid to lactic acid. c. Aerobic respiration, which oxidizes pyruvic acid to carbon dioxide and water. 2. Coenzymes are vitally important to these reactions as agents that remove electrons in the form of hydrogen atoms from intermediates. a. The two coenzymes of special important to glucose catabolism are nicotinamide adenine dinucleotide (NAD+), derived from niacin, and flavin adenine dinucleotide (FAD), derived from riboflavin. b. Hydrogen atoms are removed from intermediates in pairs and transferred to coenzymes. c. The reduced coenzymes have a higher free energy content and act as temporary energy carriers. i. FAD + 2H FADH2 ii. NAD+ + 2H NADH + H+ C. Upon entering a cell, glucose begins a series of conversion reactions called glycolysis. (pp. 1026–1027) (Fig. 26.3) Saladin Outline Ch.26 Page 13 1. Phosphorylation is accomplished by the enzyme hexokinase, which transfers an inorganic phosphate (Pi) from ATP to glucose, producing glucose 6-phosphate (G6P); this has two effects. a. It keeps the intracellular concentration of glucose low, maintaining a concentration gradient. b. Phosphorylated compounds cannot pass through the membrane, so the sugar cannot leave the cell. i. In most cells, step 1 is irreversible because they lack a reversing enzyme. ii. Exceptions are cells that must be able to release glucose to the blood, namely absorptive cells of the small intestine, proximal convoluted tubule cells in the kidney, and liver cells. c. G6P can be converted to fat, amino acids, or glycogen, or can be further oxidized to extract energy. 2. Priming involves rearrangement (isomerization) of G6P to fructose 6-phosphate, which is phosphorylated again to form fructose 1,6-diphosphate. a. This primes the process by providing activation energy. b. Two ATP have been consumed in steps 1 and 2 to get the process going; later, much more ATP will be produced. 3. Cleavage splits fructose 1,6 diphosphate into two three-carbon molecules (C3), generating two molecules of phosphoglyceraldehyde (PGAL), also known as glyceraldehydes 3-phosphate. 4. Oxidation then removes a pair of hydrogen atoms from each PGAL. a. The electrons and one proton are picked up by NAD + and the other proton is released into the cytosol (NADH + H+). b. A phosphate group (Pi) is also added to each of the C3 fragments, not from ATP but from the cell’s pool of free ions. 5. Dephosphorylation occurs in the next two steps, as phosphate groups are taken from the glycolysis intermediates and transferred to ADP, converting it to ATP; the C3 compound becomes pyruvic acid. a. The end products are 2 pyruvic acid + 2 NADH + 2H+ + 2ATP. b. Four ATP are produced, but 2 ATP were consumed in steps 1 and 2, so the net gain is 2 ATP per glucose. D. Anaerobic fermentation occurs when oxygen is abundant. (p. 975) 1. Some cells, such as vigorously exercising muscle cells without sufficient oxygen, and cells without mitochondria, such as RBCs, can make ATP only via glycolysis. 2. Glycolysis would come to a halt, however, unless NAD+ is regenerated. Saladin Outline Ch.26 Page 14 3. In the absence of oxygen, a cell uses a one-step reaction called anaerobic fermentation in which NADH is regenerated by donating a pair of electrons to pyruvic acid to produce lactic acid and NAD+. 4. Lactic acid leaves the cells and goes to the liver; when oxygen is plentiful again, lactic acid is oxidized in the liver back to pyruvic acid. a. The oxygen required to do this is part of the oxygen debt created by exercising skeletal muscles. b. The liver can also convert lactic acid back to G6P, and can either: i. Polymerize it to form glycogen for storage, or ii. Remove the phosphate group and release free glucose into the blood. 5. Anaerobic fermentation keep glycolysis running for awhile longer, but has some drawbacks. a. It is wasteful because most of the energy of glucose is still in lactic acid. b. Lactic acid is toxic and contributes to muscle fatigue. c. Skeletal muscle is relatively tolerant of anaerobic fermentation, and cardiac muscle is less so; the brain employs almost no anaerobic fermentation. d. During birth, the infant’s organs undergo anaerobic fermentation to allow the brain to have sufficient oxygen during the period when oxygen is unavailable. E. Aerobic respiration takes place in the mitochondria and requires oxygen as the final electron acceptor. (pp. 1027–1030) (Figs. 25.1, 25.2) 1. When oxygen is present, pyruvic acid enters the mitochondria and is oxidized in two principle steps. a. A group of reactions called matrix reactions occurs in the fluid of the mitochondrial matrix. b. Another group of reactions called membrane reactions occurs through action of enzymes in the membranes of the mitochondrial cristae. 2. The matrix reactions constitute a series called the citric acid cycle (Krebs cycle); their steps are numbered in parentheses to follow the glycolysis steps. (Fig. 26.4) a. (6) Pyruvic acid is decarboxylated to become a C2 compound. b. (7) NAD+ removes hydrogen atoms from the C2 compound (oxidation) and converts it to an acetyl group (acetic acid). c. (8) The acetyl group binds to coenzyme A (derived from pantothenic acid) to produce acetyl-coenzyme A (acetyl-CoA), which can enter the citric acid cycle. d. (9) CoA hands off the acetyl group to a C4 compound, oxaloacetic acid, to produce the C6 compound citric acid. e. (10) Water is removed and the citric acid molecule is reorganized, but still remains a C6 compound. Saladin Outline Ch.26 Page 15 f. (11) Hydrogen atoms are removed and accepted by NAD +. g. (12) Another CO2 is removed and the substrate becomes a five-carbon chain. h. (13–14) Steps 11 and 12 are essentially repeated, generating another CO 2 and a four-carbon chain. i. No more carbons are removed after this point; the substrate remains a series of C4 molecules back to the start of the cycle. ii. The three carbon atoms of pyruvic acid have all been removed as CO2 at steps 6, 12, and 14; these are the source of most CO 2 in the breath. i. (15) Some of the energy in the C4 substrate goes to phosphorylate guanosine diphosphate (GDP) to convert it to guanosine triphosphate (GTP), which quickly transfers the Pi group to ADP to make ATP; coenzyme A participates in this step. j. (16) Two hydrogen atoms are removed and accepted by FAD. k. (17) Water is added. l. (18) Two final hydrogen atoms are removed and transferred to NAD +, generating oxaloacetic acid that can start the cycle again. m. For every glucose molecule that enters glycolysis, two pyruvic acid molecules enter the matrix reaction, so the reaction occurs twice. i. The carbon atoms of the original glucose have all been carried away as CO2. ii. 2 ATP have been generated, but most energy is now in the reduced coenzymes: 8 NADH and 2 FADH2. n. The citric acid cycle is also a pathway and source of intermediates for synthesis of fats and nonessential amino acids. 3. The membrane reactions have two purposes: further oxidation of NADH and FADH 2 to transfer energy to ATP, and regeneration of NAD+ and FAD so that they are available for earlier steps. a. The membrane reactions are carried out by a series of compounds called the mitochondrial electron-transport chain. (Fig. 26.5) b. The members of the chain, which are arranged in a precise order, are as follows: i. Flavin mononucleotide (FMN), a derivative of riboflavin similar to FAD, which accepts electrons from NADH. ii. Iron–sulfur centers. iii. Coenzyme Q (CoQ), which accepts electrons from FADH2; it is a mobile molecule. Saladin Outline Ch.26 Page 16 iv. Copper ions bound to two membrane proteins. v. Cytochromes, five enzymes with iron cofactors, that participate in the order b, c1, c, a, and a3. c. The order of the electron transport through the chain is shown in Fig. 26.5. i. Hydrogen atoms are split apart as they transfer from coenzymes to the chain. ii. The protons are pumped into the intermembrane space of the mitochondrion. (Fig. 26.6) iii. Each carrier becomes reduced as it receives electrons and oxidized again as it passes them along, liberating energy at each transfer. iv. The final acceptor in the chain is oxygen; it accepts two electrons from cytochrome a3 and two protons from the mitrochondrial matrix, with water as a result. v. This is the body’s primary source of metabolic water. vi. Without oxygen, this reaction stops, the other processes halt like a traffic jam, ATP production becomes to low to sustain life, and death ensues within a few minutes. d. The chemiosmotic mechanism maintains an H+ gradient that drives ATP synthesis. i. Some of the energy liberated as electrons are passed through the chain drives the three respiratory enzyme complexes. ii. Each complex collectively acts as a proton pump that removes H+ and pumps it into the space between the inner and outer mitochondrial membranes. (Fig. 26.6) iii. Coenzyme Q shuttles electrons from the first pump complex to the second, and cytochrome c shuttles electrons from the second pump complex to the third. iv. The result is a very high H+ concentration and positive charge between the membranes creating a steep electrochemical gradient. v. The inner membrane contains H+-specific channel proteins called ATP synthase through which H+ flows. vi. The flow of H+ creates an electrical current, and ATP synthase harnesses the energy of this current to drive ATP synthesis. F. ATP production through glucose metabolism results in a theoretical maximum of 38 ATP per molecule of glucose. (p. 1031) 1. NADH releases its electron pairs (as hydrogen atoms) to FMN in the first proton pump complex, generating enough energy to synthesize 3 ATP per electron pair. Saladin Outline Ch.26 Page 17 2. FADH2 releases its electron pairs to coenzyme Q, the shuttle between the first and second proton pump complexes, contributing enough energy to synthesize 2 ATP. 3. For each glucose molecule, therefore, the production of ATP is as follows. a. 10 NADH × 3 ATP per NADH = 30 ATP generated by NADH. b. 2 FADH2 × 2 ATP per FADH2 = 4 ATP generated by FADH2. c. 2 ATP net generated by glycolysis. d. 2 ATP generated by the matrix reactions. e. The total of a.–c. is 38 ATP. 3. The amount of ATP produced per NADH differs from one cell type to another, and is still unknown for some cell types. a. NADH generated by glycolysis cannot enter the mitochondria directly, but uses a “shuttle” molecule. b. In liver, kidney, and myocardial cells, this shuttle molecule is malate, and each NADH yields 3 ATP. c. In skeletal muscle and brain cells, the shuttle is glycerol phosphate, and each NADH yields only 2 ATP. 4. Glucose has an energy content of 686 kcal/mole, and ATP has 7.3 kcal/mole, or 277.4 kcal in 38 moles. a. The maximum efficiency of aerobic respiration (ratio of energy output to input) is therefore 40%; the other 60% of the energy becomes body heat. b. Table 26.4 summarizes glucose catabolism. G. Glycogen metabolism releases stored energy. (pp. 1031–1032) 1. ATP is quickly used; it is an energy transfer molecule, not an energy storage molecule. a. Excess glucose beyond ATP requirements is converted into storage compounds, namely glycogen and fat. b. The average adult body contains about 400 to 450 g of glycogen, ¼ in the liver, ¾ in the skeletal muscles, and traces in the cardiac muscle. 2. Glycogenesis is the synthesis of glycogen, and it is stimulated by insulin. a. Glucose 6-phosphate is isomerzied to glucose 1-phosphate (G1P). b. Glycogen synthase then cleaves off the phosphate group and attaches the glucose to a growing polysaccharide chain. 3. Glycogenolysis, the hydrolysis of glycogen, releases glucose between meals, when new glucose is not being ingested. a. Glucagon and epinephrine stimulate this process. b. The enzyme glycogen phosphorylase acts on a glucose residue in glycogen, splitting it off as G1P. c. This is then isomerized to G6P, which can enter the glycolysis pathway. Saladin Outline Ch.26 Page 18 4. G6P usually cannot leave the cells that produce it; however, liver cells are an exception. a. Liver cells have glucose 6-phosphatase, which removes the phosphate and produces free glucose. b. This glucose can diffuse out of the cell into the blood, where it is available to any cells. c. Muscle cells contribute indirectly to blood glucose because they release pyruvic acid and lactic acid, which the liver can convert into glucose. 5. Gluconeogenesis is the synthesis of glucose from noncarbohydrates such as glycerol and amino acids. a. It occurs chiefly in the liver, but after lengthy fasting, the kidneys also undertake this process. b. Figure 26.8 and Table 26.5 summarize these processes. III. Lipid and Protein Metabolism (pp. 1033–1036) A. Lipogenesis is the synthesis of fats from other types of molecules, and lipolysis is the breaking down of fat for fuel. (pp. 1033–1034) 1. Triglycerides are stored primarily in the body’s adipocytes, where a given molecule may remain for 2 to 3 weeks, with continual turnover. 2. Lipogenesis occurs when ingestion exceeds the body’s needs. a. A diet high in sugars causes fat deposition and weight gain. b. Lipogenesis employs sugars and amino acids to synthesize glycerol and fatty acids, precursors of triglycerides. i. PGAL, one of the intermediates of glucose oxidation, can be converted to glycerol. ii. As glucose and amino acids enter the citric acid cycle by way of acetyl-CoA, the acetyl-CoA can also be diverted to make fatty acids. iii. The glycerol and fatty acids can then be condensed to form a triglyceride. c. The pathways are summarized in Fig. 26.9. 3. Lipolysis begins with the hydrolysis of a triglyceride into glycerol and fatty acids. (Fig. 26.9) a. This process is stimulated by epinephrine, norepineprhine, glucocorticoids, thyroid hormone, and growth hormone. b. Glycerol is easily converted to PGAL and enters glycolysis; it generates only half as much ATP as glucose, however, because it is a C3 compound. c. Fatty acid is catabolized in the mitochondrial matrix by beta oxidation, which removes two carbon atoms at a time. Saladin Outline Ch.26 Page 19 i. The resulting acetyl (C2) groups are bonded to coenzyme A to make acetyl-CoA, which enters the citric acid cycle. ii. A fatty acid of 16 carbon atoms can yield 129 molecules of ATP—a much richer source of energy than a glucose molecule; and each fat molecule contains three fatty acids. d. Excess acetyl groups can be metabolized by the liver in a process called ketogenesis. i. Two acetyl groups are condensed to form acetoacetic acid, and some is further converted to β-hydroxybutyric acid and acetone. ii. These three compounds are the ketone bodies. iii. Some cells can convert acetoacetic acid back to acetyl-CoA for passage to the citric acid cycle; however, when the body is rapidly oxidizing fats, ketone bodies accumulate. iv. This causes the ketoacidosis typical of type 1 diabetes. e. Acetyl-CoA cannot go backward up the pathway and produce glucose, because this pathway is irreversible past the point of pyruvic acid; thus, fatty acids cannot be used for gluconeogenesis. f. Without sufficient carbohydrate, fats cannot be completely oxidized because oxaloacetic acid become unavailable as a pickup molecule. g. Fat oxidation then produces excess ketones, leading to ketosis and potentially to ketoacidosis, a dangerous condition. B. Protein is broken down to form an amino acid pool that cells can draw on to make new proteins. (pp. 1034–1035) 1. About 100 g of tissue protein breaks down each day into free amino acids. 2. The fastest rate of tissue protein turnover is in the intestinal mucosa, where epithelial cells are replaced rapidly. 3. Of the amino acids absorbed by the small intestine, 50% is from the diet, 25% from dead epithelial cells, and 25% from enzymes that have been digested by each other. 4. Some amino acids in the pool can be converted to others. 5. Free amino acids can be converted to glucose or fat or used directly as fuel. 6. Three processes are involved in these conversions: a. Deamination, the removal of an amino group. b. Amination, the addition of an amino group. c. Transamination, the transfer of an amino group from one molecule to another. 7. The first step in using amino acids as fuel is to deaminate them. a. The remainder of the molecule after the –NH2 group is removed is called a keto acid. Saladin Outline Ch.26 Page 20 b. Depending on the amino acid involved, the keto acid may be converted to pyruvic acid, acetyl-CoA, or one of the acids in the citric acid cycle. c. Some of these reactions are reversible, and when an amino acid deficiency occurs, citric acid cycle intermediates may be aminated to compensate. d. In gluconeogenesis, keto acids are used to synthesize glycose. 8. When an amino acid is deaminated, its amino group is transferred to α-ketoglutaric acid, a citric acid cycle intermediate, to convert it to glutamic acid; this is a transamination. a. Glutamic acid can travel from any cell to the liver, where it is deaminated back to α-ketogluaric acid. b. The ammonia that results is toxic and enters the urea cycle, by which the liver produced a less-toxic waste, urea. c. Urea is excreted in the urine as a nitrogenous waste. d. If a diseased liver cannot carry out the urea cycle, ammonia accumulates and death from hepatic coma may ensue in a few days. 9. Protein synthesis is a complex process involving DNA, mRNA, tRNA, ribosomes, and the rough ER. a. It is stimulated by growth hormone, thyroid hormones, and insulin. b. It requires a supply of all amino acids; the eight essential amino acids must be obtained from the diet. C. The liver plays a variety of roles in metabolic processes, especially carbohydrate, lipid, and protein metabolism (p. 1035) 1. The overwhelming majority of its functions are nondigestive, even though it is regarded as a digestive gland. (Table 26.6) 2. All of the nondigestive functions except for phagocytosis are performed by the cuboidal hepatocytes. 3. Degenerative liver diseases such as hepatitis, cirrhosis, and cancer are especially lifethreatening. Insight 26.3 Hepatitis and Cirrhosis IV. Metabolic States and Metabolic Rate (pp. 1036–1038) A. Metabolism changes from hour to hour depending on intake; for 4 hours after a meal, one is in the absorptive (fed) state, and in the late morning, late afternoon, and overnight one is in the postabsorptive (fasting) state. (p. 1036) (Table 26.7) B. In the absorptive state, blood glucose is readily available for ATP synthesis. (pp. 1036–1037) 1. The status of major nutrient classes during the absorptive phase is as follows. a. Carbohydrates. Absorbed sugars are transported by the hepatic portal system to the liver. Saladin Outline Ch.26 Page 21 i. Most glucose passes through and becomes available to cells throughout the body. ii. Glucose beyond what’s needed immediately is absorbed by the liver and may be converted to glycogen or fat. iii. Most fat synthesized in the liver is released into the circulation and treated like dietary fat. b. Fats. Fats enter the lymph as chylomicrons and initially bypass the liver. i. Lipoprotein lipase removes fats from the chylomicrons for uptake, especially by adipose and muscular tissue. ii. The liver disposes of chylomicron remnants. iii. Fats are the primary energy substrate for hepatocytes, adipocytes, and muscle cells. c. Amino acids. Like sugars, these first circulate to the liver, where most pass through, but some are removed and have one of three fates. i. They are used for protein synthesis. ii. They are deaminated and used as fuel for ATP synthesis. iii. They are deaminated and used for fatty acid synthesis. 2. The absorptive state is regulated largely by insulin, which is secreted in response to elevated blood glucose and amino acid levels and also in response to gastrin, secretin, CCK, and GIP. a. Insulin regulates the rate of glucose uptake by nearly all cells except neurons, kidney cells, and erythrocytes. b. It has the following effects on its target cells. i. It increases the cellular uptake of glucose as much as 20-fold. ii. It stimulates glucose oxidation, glycogenesis, and lipogenesis. iii. It inhibits gluconeogenesis. iv. It stimulates active transport of amino acids into cells and promotes protein synthesis. v. It acts on the brain as an adiposity signal, an index of the body’s fat stores. c. A high-protein, low-carbohydrate meal does not create a risk of hypoglycemia because a high amino acid level stimulates the secretion of both insulin and glucagon. i. Glucogon is an insulin antagonist. ii. It supports an adequate level of blood glucose to meet the brain’s needs. Saladin Outline Ch.26 Page 22 C. During the postabsorptive state, blood glucose homeostasis is maintained within a range of 90– 100 mg/dL. 1. This is especially critical to the brain, which cannot use alternative energy substrates except in prolonged fasting. 2. The postabsorptive status of major nutrients is as follows. a. Carbohydrates. Glucose is drawn from the glycogen reserves (glycogenolysis) or synthesized from other compounds (gluconeogenesis). i. The liver usually stores enough glycogen to support 4 hours of postabsorptive metabolism. b. Fats. Adipocytes and hepatocytes hydrolyze fats and convert the glycerol to glucose. i. Free fatty acids cannot be converted to glucose, but they can favorably affect blood glucose concentration. ii. Cells are able to absorb and use ketone bodies generated from FFAs or use FFAs directly for energy. iii. By switching from glucose to fatty acid catabolism, they leave glucose for use by the brain. iv. After 4 to 5 days of fasting, the brain begins to use ketone bodies as supplemental fuel. c. Proteins. If glycogen and fat reserves are depleted, the body begins to use proteins as fuel. i. Some proteins are more resistant to breakdown, such as collagen. ii. Muscle protein goes quickly. iii. Extreme wasting away seen in cancer and some other diseases result from a loss of appetite as well as altered metabolism, is called cachexia. 3. The postabsorptive state is regulated mainly by the sympathetic nervous system and glucagon, but several other hormones are involved. a. Postabsorptive metabolism is more complex that that of the absorptive state. b. As blood glucose level drops, insulin secretion declines and the pancreatic alpha cells secrete glucagon. i. Glucagon promotes glycogenolysis and gluconeogenesis to restore blood glucose homeostasis. ii. It also promotes lipolysis and a rise in free fatty acid levels. c. The sympathoadrenal system also promotes glycogenolysis and lipolysis, especially under conditions of injury, fear, anger, and other stress. i. Adipose tissue is richly innervated by the sympathetic nervous system. Saladin Outline Ch.26 Page 23 ii. Adipocytes, hepatocytes, and muscle cells respond to epinephrine from the adrenal medulla. d. Stress also stimulates the release of cortisol, which promotes fat and protein catabolism and gluconeogenesis. e. Growth hormone is secreted in response to a rapid drop in blood glucose level and in conditions of prolonged fasting; it opposes insulin and raises blood glucose. D. Metabolic rate is the amount of energy liberated in the body per unit of time, expressed as kcal/h or kcal/day. (p. 1038) 1. Metabolic rate can be measured directly in a calorimeter, a closed chamber with water filled walls that absorb the heat given off by the body. a. The rate of energy is calculated from the temperature change of the water in a set period of time. 2. Metabolic rate can also be measured indirectly with a spirometer, an apparatus that measures oxygen consumed. a. For every liter of oxygen, approximately 4.82 kcal of energy is released from organic nutrients. 3. Metabolic rate depends on physical activity, mental state, absorptive or postabsorptive status, thyroid hormone and other hormones, and other factors. 4. The basal metabolic rate (BMR) is a baseline or standard of comparison that minimizes the effects of such variables. a. It is the metabolic rate when one is awake but relaxed, in a comfortable room, in a postabsorptive state 12 to 14 hours after the last meal. b. It is not the minimum metabolic rate needed to sustain life, however. c. Total metabolic rate (TMR) is the sum of BMR and the energy expenditure for voluntary activities, especially muscular contractions. 6. The BMR of an average adult male is about 2,000 kcal/day for a male and slightly less for a female. a. Even a sedentary lifestyle requires another 500 kcal/day. b. Someone who does hard physical labor may require as much as 5,000 kcal/day. 7. Some factors that raise TMR include pregnancy, anxiety, fever, eating, and the catecholamine and thyroid hormones. a. TMR is relatively high in children and declines with age. 8. Some factors that lower TMR include apathy, depression and prolonged starvation. a. In weight-loss diets, loss is often rapid at first and then goes more slowly. Saladin Outline Ch.26 Page 24 b. Because TMR drops over time, fewer dietary calories are “burned off,” and there is more lipogenesis even with the same caloric intake. c. As food intake is reduced, the body reduces its metabolic rate to conserve body mass. V. Body Heat and Thermoregulation (pp. 1038–1042) A. Thermoregulation is the balance between heat production and loss; hypothermia, a low body temperature, can slow metabolism and lead to death, whereas hyperthermia, excessively high boyd temperature, can disrupt the pace of metabolism and also lead to death. (p. 1039) B. Normal body temperature depends on when, where, and in whom it is measured. (p. 1039) 1. It tends to be lowest in the early morning and highest in the late afternoon, and varies from one place in the body to another. 2. The core temperature is the temperature of organs in the cranial, thoracic, and abdominal cavities. a. Rectal temperature is relatively easy to measure and is usually 37.2° to 37.6°C (99.0° to 99.7°F). 3. Shell temperature is the temperature closer to the surface, especially skin and oral temperature. a. Adult oral temperature is typically 36.6° to 37.0°C (97.9° to 98.6°F). b. It may be as high as 40°C (104°F) during hard exercise. C. Most body heat comes from exergonic reactions such as nutrient oxidation and ATP use; heat is lost by radiation, conduction, and evaporation. (p. 1039) 1. At rest, most heat is generated by the brain, heart, liver, and endocrine glands, with the skeletal muscles contributing about 20% to 30% of the total. 2. In vigorous exercise, however, the skeletal muscles produce 30 to 40 times as much heat as the rest of the body. 3. The body loses heat in three ways. a. Radiation is the emission of infrared (IR) rays by moving molecules; heat means molecular motion, and all molecular motion produced IR rays. i. When IR radiation is absorbed, molecular motion increases and temperature rises. ii. Our bodies continually receive IR from objects around us and give IR off to the surroundings. b. Conduction is the transfer of kinetic energy from molecule to molecule as they collide. i. The warmth of the body adds to the molecular motion and temperature of clothes you wear, the chair you sit in, and the air around you—all of which you are in contact with. Saladin Outline Ch.26 Page 25 ii. Conductive heat loss is aided by convection, the motion of a fluid due to uneven heating, such as warm air, which rises from the body. (Fig. 26.11) c. Evaporation is the change from a liquid to a gaseous state, as when water evaporates. i. The cohesion of water molecules hampers their vibratory movement in response to heat input. ii. Evaporation of water therefore carries a substantial amount of heat with it (0.58 kcal/g). iii. Perspiration wets the skin surface, and its evaporation carries heat away. iv. In extreme conditions, the body can lose 2 L or more of sweat per hour and dissipate up to 600 kcal/h of heat by evaporative loss. v. Forced convection, such as from a fan or a breeze, enhances heat loss by conduction and evaporation; it has no effect on radiation. 4. A nude body at an air temperature of 21°C (70°F) loses about 60% of its heat by radiation, 18% by conduction, and 22% by evaporation. 5. If air temperature is higher than skin temperature, evaporation becomes the only means of heat loss because radiation and conduction add more heat to the body; high humidity hinders even evaporative cooling. D. Thermoregulation is achieved through several negative feedback loops. (pp. 1040–1041) 1. The preoptic area of the hypothalamus functions as a hypothalamic thermostat. a. It monitors the temperature of the blood and receives signals also from peripheral thermoreceptors in the skin. b. It sends signals either to the heat-loss center, more anteriorly in the hypothalamus, or to the heat-promoting center, a posterior nucleus near the mammillary bodies. c. The heat loss center activates heat-losing mechanisms, including cutaneous vasodilation and sweating. d. The heat-promoting center activates mechanisms to conserve heat or generate more, such as cutaneous vasoconstriction, piloerection (good bumps), and shivering and nonshivering thermogenesis. i. Shivering involves a spinal reflex that causes tiny alternative contractions in antagonistic muscle pairs. ii. Every muscle contraction releases heat from ATP, and shivering can increase the body’s heat production as much as fourfold. Saladin Outline Ch.26 Page 26 iii. Nonshivering thermogenesis is a longer-term mechanisms for generating heat, especially during colder seasons. iv. The sympathetic nervous system and thyroid hormone stimulate an increase in metabolic rate, which can rise as much as 30% after several weeks of cold weather. v. Infants can generate heat by breaking down brown fat, a tissue in which lipolysis is not linked to ATP synthesis, so all energy is released as heat. 2. Behavioral thermoregulation is of great importance to homeostasis. a. Moving out of the sun greatly cuts down on heat gain by radiation. b. Removing clothing helps to cool the body by increasing radiation, conduction, and evaporation. E. Disturbances to thermoregulation can involve positive feedback loops and eventual death. (p. 1041) 1. Fever is a normal protective mechanism that should be allowed to run its course unless it becomes excessively high. a. A body temperature above 42° to 43°C (108° to 110°F) can be very dangerous. b. The metabolic rate increases and heat is generated faster than it can be dispersed. c. Thus the fever begins a dangerous positive feedback loop. d. At a body temperature of 44° to 45°C (111° to 113°F) metabolic dysfunction and neurological damage can be fatal. 2. Excessive heat from other sources cause heat cramps, heat exhaustion, and heatstroke. a. Heat cramps are painful muscle spasms that result from excessive electrolyte loss in sweat. i. They occur especially when a person begins to relax after strenuous exertion and heavy sweating. b. Heat exhaustion results from more severe water and electrolyte loss, and is characterized by hypotension, dizziness, vomiting, and sometimes fainting. c. Heatstroke or sunstroke is a life-threatening condition that often kills people during prolonged heat waves, especially with high humidity. i. Humidity retards evaporative cooling. ii. Heatstroke is clinically defined as a state in which core body temperature is over 40°C (104°F), the skin is hot and dry, and the subject exhibits nervous system dysfunctions such as delirium, convulsions, or coma. Saladin Outline Ch.26 Page 27 iii. It is also accompanied by tachycardia, hyperventilation, inflammation, and multiorgan disfunction. 3. Hypothermia can result from exposure to cold weather or immersion in icy water. a. If the core temperature drops below 33°C (91°F) the metabolic rate drops so low that heat production cannot keep page with heat loss, and the temperature falls even more. b. Death from cardiac fibrillation may occur below 32°C (90°F), but some people survive body temperatures as low as 29°C (84°C) in a state of suspended animation. c. A body temperature below 24°C (75°F) is usually fatal. d. Alcohol should not be given to someone in a state of hypothermia; it produces an illusion of warmth but actually accelerates heat loss by dilating blood vessels. Insight 26.4 Alcohol and Alcoholism Cross Reference Additional information on topics mentioned in Chapter 26 can be found in the chapters listed below. Chapter 4: Protein synthesis Chapter 17: Insulin and glucagon Chapter 21: Fever Chapter 22: Use of the spirometer Chapter 23: Nitrogenous wastes and their sources Chapter 24: Thirst Chapter 24: The phosphate buffer system