Chapter 25: Energetics

1. Chapter 25: Energetics

2. Metabolism A term referring to all chemical reactions necessary to maintain life. Substances are constantly being broken down and built up. Anabolism: larger molecules are built from small ones (like AA�s?proteins) Catabolism: complex structures broken down into simpler ones (digestion)

3. The Nutrient Pool Contains all organic building blocks cell needs: to provide energy to create new cellular components Is source of substrates for catabolism and anabolism 6 categories of nutrients Carbohydrates Lipids Proteins Vitamins Minerals Water

4. Carbohydrates Dietary sources Predominately plants Sugars � fruits, honey, milk, candy, soda Starch � grains, legumes, root veggies Cellulose � veggies (not digested but provides fiber to facilitate defecation) Dietary requirements: When less than 50 grams/day are consumed, tissue proteins and fats are broken down for energy fuel

5. Carbohydrates, cont. Uses in the body Glucose (monosaccharide) is a major body fuel and is readily used to make ATP Carbohydrate digestion also yields fructose and galactose but the liver converts them to glucose before entering general circulation Small amounts are used for nucleic acid synthesis Various sugars attach to external plasma membrane proteins and lipids *when glucose is present in excess of what the body needs for ATP synthesis, it is converted to glycogen or fat and stored for later use*

6. Lipids Dietary sources Saturated fats Animal products (meat & dairy) & a few plants (coconut, palm, palm kernal oils) Unsaturated fats Seeds, nuts, most veggie oils Dietary requirements Higher for infants/children than for adults AHA recommends <30% of total caloric intake <10% saturated fats Daily cholesterol should not exceed 200 mg

7. Lipids, cont. Uses in the body Dietary fats help the body absorb fat-soluble vitamins, triglycerides are the major E source for liver cells & skeletal mm, phospholipids are a major component of the myelin sheaths and ALL cellular membranes Fat deposits provide: protection around organs, insulation, concentrated E source Cholesterol is not used as an E source. It is a stabilizer for cell membranes and a precursor to bile salts, steroid H�s, and other essential functional molecules

8. Proteins Most abundant organic components in body Dietary sources Primarily animal products (eggs, milk, meat) Legumes, nuts, & cereals are nutritionally incomplete because they are low in one or more essential AA�s Cereal grains and legumes together provide all of the essential AA�s Dietary requirements Most Americans eat far more protein than they need Must ingest essential AA�s

9. Proteins, cont. Uses in the body Structural materials (collagen, elastin, keratin) Functional proteins (enzymes, hemoglobin, H�s) Hormonal controls Anabolic hormones accelerate protein synthesis i.e. growth hormone, sex hormones, adrenal glucocorticoids, etc� Whether AA�s are used to synthesize new proteins or are burned for E depends on a number of factors�

10. Proteins, cont. Adequacy of caloric intake For protein synthesis you must have adequate intake of carb�s & fats for ATP production If not�dietary & tissue proteins are used for E Nitrogen balance of body Healthy adults: protein synthesis = protein breakdown The body is in nitrogen balance when the amount of nitrogen ingested in proteins equal the amount excreted in urine & feces

11. Negative nitrogen balance Protein breakdown exceeds amount of protein used for synthesis Occurs w/physical & emotional stress, when quality of dietary protein is poor, and with starvation Protein synthesis>protein breakdown & loss Normal for growing children & pregnant women Normal with rebuilding of tissues following injury or illness Always more protein going into tissues than amount being broken down for E

12. Carbohydrate Metabolism Generates ATP and other high-energy compounds by breaking down carbohydrates: glucose + oxygen ? carbon dioxide + water ?

13. Energy Yield of Aerobic Metabolism For 1 glucose molecule processed, cell gains 36 molecules of ATP: 2 from glycolysis 4 from NADH generated in glycolysis 2 from TCA cycle (through GTP) 28 from ETS

14. Carbohydrate Breakdown and Synthesis Gluconeogenesis - the synthesis of glucose from noncarbohydrate precursors: lactic acid, glycerol, & AA�s Stores glucose as glycogen in liver and skeletal muscle Glycogenesis - the formation of glycogen from glucose Glycogenolysis - Is the breakdown of glycogen

15. Lipolysis Breaks lipids down into pieces that can be converted to pyruvic acid & channeled directly into TCA cycle Hydrolysis splits triglyceride into component parts: 1 molecule of glycerol & 3 fatty acid molecules Different enzymes convert fatty acids to acetyl-CoA (beta-oxidation)

16. 3 Energy Benefits of Beta-Oxidation For each 2-carbon fragment removed from fatty acid, cell gains: 12 ATP from acetyl-CoA in TCA cycle 5 ATP from NADH Cell can gain 144 ATP molecules from breakdown of one 18-carbon fatty acid molecule Fatty acid breakdown yields about 1.5 times the energy of glucose breakdown

17. Lipid Synthesis Also called lipogenesis Can use almost any organic substrate: because lipids, amino acids, and carbohydrates can be converted to acetyl-CoA

18. Lipid Transport Cells require lipids to maintain cell membranes Steroid hormones must reach target cells in many different tissues Most lipids are not soluble in water: special transport mechanisms carry lipids from one region of body to another Most lipids circulate through bloodstream as lipoproteins Free fatty acids are a small percentage of total circulating lipids

19. Free Fatty Acids (FFAs) Are lipids that can diffuse easily across cell membranes In blood, are generally bound to albumin (most abundant plasma protein) Are an important energy source: during periods of starvation when glucose supplies are limited Liver cells, cardiac muscle cells, skeletal muscle fibers, etc. metabolize free fatty acids

20. Lipid Transport and Utilization

21. Lipoproteins Are used to transport triglycerides & cholesterol (since they do not circulate free in the bloodstream) They all contain triglycerides, phospholipids, & cholesterol in addition to protein The higher the % of lipid in the lipoprotein, the lower its� density�the higher the % of protein, the higher its� density 5 Classes of Lipoproteins Chylomicrons Very low-density lipoproteins (VLDLs) Intermediate-density lipoproteins (IDLs) Low-density lipoproteins (LDLs) High-density lipoproteins (HDLs)

22. Chylomicrons Are produced in intestinal tract & are too large to diffuse across capillary wall Enter lymphatic capillaries (lacteals) Travel through thoracic duct: to venous circulation and systemic arteries

23. Distribution of Other Lipoproteins Lipoprotein lipase removes many triglycerides from VLDLs, leaving IDLs When IDLs reach liver additional triglycerides are removed & broken down into fatty acids and monoglycerides protein content of lipoprotein is altered & LDLs are created LDLs are transported to peripheral tissues to deliver cholesterol

24. Very low density lipoproteins (VLDL) Primary source is liver transports triglycerides from liver to peripheral tissues (mainly adipose tissue)

25. Low-density lipoproteins (LDL) Transports cholesterol to the peripheral tissues makes it available to tissue cells for membrane or hormone synthesis & stores it for later use also regulates cholesterol synthesis in the tissue cells

26. High-density lipoproteins (HDL) Transports excess cholesterol from peripheral tissues to the liver gets broken down & becomes part of bile

27. Plasma cholesterol levels HDL (�good-cholesterol�) 35-60 is ok; above 60 may protect against heart disease LDL (�bad cholesterol�) levels above 160 is considered bad b/c of propensity to deposit cholesterol in artery walls

28. Factors regulating plasma cholesterol levels Diet modification may help but the liver will still maintain a basal production of cholesterol saturated fats (+) liver synthesis of cholesterol & (-) secretion from body unsaturated fats enhance secretion of cholesterol & its catabolism to bile salts trans-fatty acids (hydrogenated unsat FAs) cause serum changes worse than sat FAs omega-3 FAs (some cold water fishes) reduce saturated fat & cholesterol levels & have antiarrhythmic effect on heart & make platelets less sticky smoking, stress, coffee, increase LDL levels aerobic exercise lowers LDLs & increases HDLs �apples� have higher cholesterol than �pears� typically

29. Proteins The body synthesizes 100,000 to 140,000 proteins: each with different form, function, and structure All proteins are built from the 20 amino acids

30. Protein Metabolism Cellular proteins are recycled in cytosol: peptide bonds are broken free amino acids are used in new proteins If other energy sources are inadequate: mitochondria generate ATP by breaking down amino acids in TCA cycle Not all amino acids enter cycle at same point, so ATP benefits vary

31. Proteins and ATP Production When glucose and lipid reserves are inadequate, liver cells: break down internal proteins absorb additional amino acids from blood Amino acids are deaminated: carbon chains broken down to provide ATP

32. 3 Factors Against Protein Catabolism Proteins are more difficult to break apart than complex carbohydrates or lipids A by-product, ammonium ion, is toxic to cells Proteins form the most important structural and functional components of cells

33. Protein Synthesis The body synthesizes half of the amino acids needed to build proteins (Nonessential AA�s) amino acids made by the body on demand 10 essential AA�s: 8 not synthesized: isoleucine, leucine, lysine, threonine, tryptophan, phenylalanine, valine, and methionine 2 insufficiently synthesized: arginine and histidine

34. Summary: Pathways of Catabolism and Anabolism

35. Metabolic Interactions Body has 2 patterns of daily metabolic activity: absorptive state postabsorptive state

36. The Absorptive State Is the period following a meal when nutrient absorption is under way Primarily an anabolic phase w/glucose as main E source most excess metabolites will be converted to fat for storage if not used in anabolism carbs-->liver to covert to glu-->released to blood or makes & stores glycogen & makes fat to release to blood for storage by adipocytes triglycerides-->FA�s + glycerol-->sk mm, liver cells, & adipocytes use FA�s as primary E source-->most FA�s & glycerol re-enter adipose tissue & reconvert to triglycerides for storage AA�s-->some to liver for deamination to keto acids-->Kreb�s for ATP formation or conversion to liver fat stores; liver uses some AAs for plasma protein synthesis but most go into general circulation for uptake by other body cells to use for anabolism

37. The Postabsorptive State When nutrient absorption is not under way (fasting state) Primarily catabolic to maintain blood glucose levels w/in normal range b/t meals glycogenolysis in liver can maintain blood glu levels for ~ 4 hrs glycogenolysis in skeletal mm - glucose cannot be released to blood as w/liver (lacks all necessary enzymes) but�partial oxidation to pyruvic acid (or lactic acid) occurs-->goes to liver for conversion back to glucose & is released to blood lipolysis in adipose tissue & liver -->leads to glycerol-->liver converts to glucose & releases to the blood catabolism of cellular protein - primary source of blood glucose w/fasting (glycogen stores are depleted)-->AAs are deaminated & coverted to glucose in liver & are released to blood

38. Regulatory Hormones: Effects on Peripheral Metabolism

39. Lipid and Amino Acid Catabolism Generates acetyl-CoA�Increased [ ] of acetyl-CoA causes ketone bodies to form Ketone Bodies are acids that dissociate in solution Fasting produces ketosis: a high concentration of ketone bodies in body fluids Liver cells do not catabolize ketone bodies: compounds diffuse into general circulation peripheral cells absorb ketone bodies Cells reconvert ketone bodies to acetyl-CoA for TCA cycle

40. Ketonemia is the appearance of ketone bodies in bloodstream Lowers plasma pH, which must be controlled by buffers Ketoacidosis is a dangerous drop in blood pH: caused by high ketone levels exceeding buffering capacities Severe Ketoacidosis - Circulating concentration of ketone bodies can reach 200 mg dl: pH may fall below 7.05 may cause coma, cardiac arrhythmias, death

41. 4 Types of Nitrogen Compounds Amino acids: framework of all proteins, glycoproteins, and lipoproteins Purines and pyrimidines: nitrogenous bases of RNA and DNA Creatine: energy storage in muscle (creatine phosphate) Porphyrins: bind metal ions essential to hemoglobin, myoglobin, and cytochromes

42. Nitrogen Balance Occurs when: nitrogen absorbed from diet balances nitrogen lost in urine and feces Nitrogen atoms are not stored in the body . They must be obtained by: recycling N in body or from diet

43. Negative nitrogen balance Protein breakdown (excretion) exceeds amount of protein used for synthesis Occurs w/physical & emotional stress, when quality of dietary protein is poor, and with starvation Protein synthesis (absorption) >protein breakdown & loss Normal for growing children & pregnant women Normal with rebuilding of tissues following injury or illness Always more protein going into tissues than amount being broken down for E

44. Minerals and Mineral Reserves

45. Minerals Make up 4% of body weight and are not used for fuel Body requires moderate amounts of 7 types (Na,P, K,S,Na,Cl, & Mg) & trace amounts of ~ a dozen others Uses include strength (Ca/P/Mg), electrolytes (Na/Cl/K), bind to organic compounds to form molecules like phospholipids, hormones, & enzymes Found mostly in veggies, legumes, milk, & some meats

46. Vitamins Organic compounds needed for growth & health Most serve as coenzymes (or parts of coenzymes) w/o them the carb�s, proteins, & fats we eat would be useless Some act as antioxidants (A,C,E) and act against cancer causing free radicals Are not used for energy Do not serve as building blocks Most are not made in the body and must be ingested (exceptions: D-skin, B/K-intestinal bacteria)

47. Vitamins, cont. Fat soluble (Vit�s A,D,E,& K) Bind to ingested lipids and are absorbed w/ their digestion products Problem w/fat absorption�problem w/uptake of fat soluble vitamins Can have hypervitaminosis Water soluble (all others) Absorbed thru intestinal tract Typically can not overdose; pee out excess

48. Fat Soluble Vitamins Vitamin A - A structural component of visual pigment retinal Vitamin D - Is converted to calcitriol: which increases rate of intestinal calcium and phosphorus absorption Vitamin E - Stabilizes intracellular membranes Vitamin K - Helps synthesize several proteins including 3 clotting factors

49. The Fat-Soluble Vitamins

50. The Water-Soluble Vitamins

51. Vitamins and Bacteria Bacterial inhabitants of intestines produce small amounts of: fat-soluble vitamin K 5 water-soluble vitamins including B12 Intestinal epithelium absorbs all water-soluble vitamins except B12 B12 molecule is too large & must bind to intrinsic factor before absorption

52. Energy Gains and Losses Energy is released when chemical bonds are broken In cells energy is used to synthesize ATP some energy is lost as heat Lipids release 9.46 C/g Carbohydrates release 4.18 C/g Proteins release 4.32 C/g

53. Calories Energy required to raise 1 g of water 1 degree centigrade is a calorie Energy required to raise 1 kg of water 1 degree centigrade is a Calorie (C)

54. Metabolism Clinicians examine metabolism to determine Calories used and measured in: Calories /hr, Calories/day, Calories /unit of body wt/day Metabolic rate is the sum of all anabolic and catabolic processes in the body If daily energy intake exceeds energy demands body stores excess energy as triglycerides in adipose tissue If daily caloric expenditures exceeds dietary supply body uses energy reserves, loses weight

55. Basal Metabolic Rate (BMR) Is the minimum resting energy expenditure: of an awake and alert person measured under standardized testing conditions Involves monitoring respiratory activity Energy utilization is proportional to oxygen consumption

56. Hormonal Effects Thyroxine: controls overall metabolism Cholecystokinin (CCK): suppresses appetite Adrenocorticotropic hormone (ACTH): suppresses appetite Leptin: released by adipose tissues during absorptive state binds to CNS neurons that suppress appetite

57. Heat Production BMR estimates rate of energy use Energy not captured is released as heat: serves important homeostatic purpose

58. Thermoregulation The body produces heat as by-product of metabolism Increased physical or metabolic activity generates more heat Heat produced is retained by water in body For body temperature to remain constant: heat must be lost to environment Body controls heat gains and losses to maintain homeostasis

59. Mechanisms of Thermoregulation The body uses four mechanisms of heat exchange Radiation (50%) � loss of heat as infrared rays Conduction � transfer of heat by direct contact Convection (15%) � transfer of heat to the surrounding air Evaporation � heat loss due to the evaporation of water from the lungs, mouth mucosa, and skin (insensible heat loss) Evaporative heat loss becomes sensible when body temperature rises and sweating produces increased water for vaporization

60. Insensible Water Loss - about 20% of indoor heat loss Each hour, 20�25 ml of water crosses epithelia & evaporates from alveolar surfaces and skin surface Sensible Perspiration - from sweat glands Depends on wide range of activity from inactivity to secretory rates of 2�4 liters/hr

61. Regulating Heat Gain and Loss Is coordinated by heat-gain center and heat-loss center in anterior hypothalamus

62. 3 Actions of Heat-Loss Center Inhibition of vasomotor center: causes peripheral vasodilation & warm blood flows to surface of body skin temperatures rise & radiational and convective losses increase Sweat glands are stimulated to increase secretory output: perspiration flows across body surface & evaporative heat losses increase Respiratory centers are stimulated: depth of respiration increases

63. Mechanisms for Promoting Heat Gain The heat-gain center prevents low body temperature (hypothermia) Sympathetic vasomotor center decreases blood flow to dermis reducing losses by radiation, convection, and conduction In cold conditions blood flow to skin is restricted blood returning from limbs is shunted to deep, insulated veins (countercurrent exchange)

64. Countercurrent Exchange Is heat exchange between fluids moving in opposite directions: traps heat close to body core & restricts heat loss in cold conditions Blood is diverted to a network of deep, insulated veins Venous network wraps around deep arteries Heat is conducted from warm blood flowing outward to cooler blood returning from periphery

65. Heat Generation Shivering thermogenesis Increased muscle tone increases energy consumption of skeletal muscle�energy consumption produces heat Involves both agonists and antagonists Shivering increases heat generation up to 400% Nonshivering thermogenesis Releases hormones that increase metabolic activity Raises heat production in adults 10�15% over extended time period

66. Hormones and Thermogenesis Heat-gain center stimulates adrenal medullae via SNS division of ANS releasing epinephrine Epinephrine increases glycogenolysis in liver and skeletal muscle & the metabolic rate of most tissues In children, low body temperature stimulates additional TRH release, stimulating thyroid-stimulating hormone (TSH) TSH stimulates thyroid gland increasing thyroxine release into blood Thyroxine increases rate of carbohydrate catabolism & rate of catabolism of all other nutrients

67. Infant Thermogenesis Mechanism Infants have brown fat: highly vascularized adipose tissue adipocytes contain numerous mitochondria found between shoulder blades, around neck, and in upper body Pyrexia is elevated body temp. (Usually temporary) Fever is body temperature maintained at greater than 37.2?C (99?F) Occurs for many reasons, not always pathological In young children, transient fevers can result from exercise in warm weather