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Chapter 26 Lecture Outline

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1 Chapter 26 Lecture Outline
See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2 Nutrition and Metabolism
Carbohydrate Metabolism Lipid and Protein Metabolism Metabolic States and Metabolic Rate Body Heat and Thermoregulation

3 Body Weight Stable with equal energy intake and output
around a homeostatic set point Determined by combination of environmental and hereditary factors 30-50% of variation between individuals due to heredity rest due to eating and exercise habits

4 Gut-Brain Peptides Appetite regulators short term long term
effects last minutes to hours long term effects last weeks to years

5 Short-term Appetite Regulators
Ghrelin – produces hunger Peptide YY – satiety Cholecystokinin – satiety

6 Short-term Appetite Regulators
Ghrelin – hunger from parietal cells of empty stomach also stimulates hypothalamus release of human growth hormone releasing hormone

7 Short-term Appetite Regulators
Peptide YY (PPY) – satiety from enteroendocrine cells in ileum and colon secreted in proportion to calories consumed acts as ileal break slows stomach emptying

8 Short-term Appetite Regulators
Cholecystokinin (CCK) – satiety from enteroendocrine cells of duodenum and jejunum appetite-suppressing effect on brain

9 Long-term Appetite Regulators
Leptin – secreted by adipocytes in proportion to body fat stores Insulin – pancreatic beta cells effect similar to leptin (but weaker)

10 Hypothalamus Receptors for gut-brain peptides that regulate release of: neuropeptide Y (hunger) stimulated by gherlin inhibited by PYY, leptin, and insulin melanocortin (satiety) stimulated by leptin, and CCK

11 Appetite Regulation

12 Other Factors in Appetite Regulation
Appetite is briefly satisfied by chewing swallowing stomach filling Neurotransmitters stimulate desire for different foods norepinephrine – carbohydrates galanin – fats endorphins – protein

13 Calories One calorie - amount of heat required to raise temperature of 1 g of water 1 °C 1000 calories is a kilocalorie or Calorie Fats contain about 9 kcal/g Carbohydrates and proteins, about 4 kcal/g sugar and alcohol are “empty” calories -- few nutrients Substance used for fuel is oxidized primarily to make ATP

14 Nutrients Ingested chemical used for growth, repair or maintenance
Macronutrients consumed in large amounts proteins, fats and carbohydrates Micronutrients needed in small amounts Recommended daily allowances (RDA) safe estimate of daily intake for standard needs Essential nutrients can not be synthesized minerals, vitamins, 8 amino acids and 1-3 fatty acids must be consumed in the diet

15 Carbohydrates Carbohydrates found in 3 places in body
muscle and liver glycogen; blood glucose Most carbohydrate serves as fuel neurons and RBCs depend on glucose Sugars do serve as structural components nucleic acids, glycoproteins and glycolipids, ATP Blood glucose carefully regulated by insulin and glucagon

16 RDA and Dietary Sources of Carbs
Carbohydrates are rapidly oxidized, RDA greater than any other nutrient (175 g/day) Dietary sources: monosaccharides = glucose, galactose and fructose liver converts galactose and fructose to glucose outside hepatic portal system, only blood sugar is glucose normal blood sugar concentration ranges 70 to 110 mg/dL disaccharides = table sugar (sucrose), maltose, lactose polysaccharides = starch, glycogen and cellulose Nearly all dietary carbohydrates come from plants

17 Dietary Fiber Fibrous material that resists digestion
Fiber is important to diet (RDA is 30 g/day) excess interferes with mineral absorption - iron Water-soluble fiber (pectin)  blood cholesterol and LDL levels Water-insoluble fiber (cellulose, lignin) absorbs water in intestines, softens stool, gives it bulk, speeds transit time

18 Lipids Average adult male 15% fat; female 25% fat body’s stored energy
hydrophobic, contains 2X energy/g, compact storage glucose and protein sparing (no protein utilized for energy) fat-soluble vitamins (A,D,E,K) absorbed with dietary fat ingest less than 20 g/day risks deficiency

19 Functions of Lipids Diverse functions structural chemical precursors
phospholipids and cholesterol are components of plasma membranes and myelin chemical precursors cholesterol - a precursor of steroids, bile salts and vitamin D fatty acids - precursors of prostaglandins and other eicosanoids

20 Fat Requirements and Sources
Should be less than 30% of daily calorie intake typical American gets 40-50% Most fatty acids synthesized by body essential fatty acids must be consumed Saturated fats animal origin -- meat, egg yolks and dairy products Unsaturated fats found in nuts, seeds and most vegetable oils Cholesterol found in egg yolks, cream, shellfish, organ meats and other meats

21 Serum Lipoproteins Lipids transported in blood as lipoproteins
protein and phospholipid coat around a hydrophobic cholesterol and triglyceride core soluble in plasma; bind to cells for absorption

22 Serum Lipoproteins Categorized into 4 groups by density: more protein = higher density chylomicrons very low-density (VLDLs) low-density (LDLs) high-density (HDLs)

23 Serum Lipoproteins

24 Chylomicrons Form in absorptive cells of small intestine
enter lymphatic system, then blood capillary endothelium has lipoprotein lipase to hydrolyze monoglycerides resulting free fatty acids (FFAs) and glycerol enter fat cells to be resynthesized into triglycerides for storage chylomicron remnant degraded by liver

25 VLDL and LDL VLDL produced by liver to transport lipids to adipose tissue for storage when triglycerides removed become LDLs (mostly cholesterol) LDL absorbed by cells in need of cholesterol for membrane repair or steroid synthesis

26 HDL Production and function liver produces an empty protein shell
travels through blood, picks up cholesterol delivers cholesterol to liver, for elimination in bile

27 Total Cholesterol Desirable to maintain total cholesterol concentration of < 200 mg/dL most cholesterol is endogenous dietary restrictions lower blood cholesterol levels by 5% with restriction of dietary cholesterol by 15 to 20% with restriction of certain saturated fats vigorous exercise lowers blood cholesterol

28 Desirable Lipoprotein Levels
High levels of HDL indicate cholesterol is being removed from arteries Low levels LDL high LDL correlates with cholesterol deposition in arteries Recommendations exercise regularly avoid smoking, saturated fats, coffee and stress

29 Lipoprotein Processing
Three pathways

30 Proteins 12-15% of body mass Functions mostly in skeletal muscles
muscle contraction movement of body, cells, cell structures cell membranes (receptors, cell identity, pumps) fibrous proteins (collagen, keratin) structural globular proteins (antibodies, myoglobin, enzymes) functional plasma proteins: blood osmolarity and viscosity

31 Requirements for Protein
RDA g/day Nutritional value depends on proportions of amino acids 8 essential amino acids can not be synthesized isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine Cells do not store surplus protein Complete proteins (dietary) supply all amino acids in right amount needed to synthesize protein

32 Dietary Sources Animal proteins (meat, eggs and dairy) are complete proteins closely match human proteins in amino acid composition Plant sources must be combined in the right proportions beans and rice are a complementary choice

33 Nitrogen Balance Rate of nitrogen ingestion equals rate of excretion
proteins are chief dietary source of nitrogen excretion chiefly as nitrogenous wastes Positive nitrogen balance occurs in children; they ingest more than they excrete promoted by growth and sex hormones Negative nitrogen balance body proteins being broken down for fuel (muscle atrophy) glucocorticoids promote protein catabolism in states of stress

34 Functions of Minerals Calcium and phosphorus Phosphorus
bones and teeth Phosphorus phospholipids, ATP, CP, buffers, nucleic acids Calcium, iron, magnesium and manganese cofactors for enzymes Iron - essential for hemoglobin and myoglobin Chlorine - component of stomach acid (HCl) Mineral salts electrolytes; govern function of nerve and muscle cells; regulate distribution of body water

35 Dietary Sources of Minerals
Vegetables, legumes, milk, eggs, fish and shellfish Animal tissues contain large amounts of salt carnivores rarely lack salt in their diets herbivores often supplement by ingesting soils Recommended sodium intake is 1.1 g/day Typical American diet contains 4.5 g/day

36 Vitamins Body synthesizes some vitamins from precursors
niacin, vitamin A and D vitamin K, pantothenic acid, biotin, folic acid produced by intestinal bacteria Water-soluble vitamins (C, B) absorbed with water in small intestine; not stored Fat-soluble vitamins (A, D, E, K) absorbed with dietary lipids; stored

37 Vitamins

38 Carbohydrate Metabolism
Dietary carbohydrate burned as fuel within hours of absorption (glucose catabolism) C6H12O6 + 6O2  6CO2 + 6H2O Transfers energy from sugar to ATP

39 Glucose Catabolism Series of small steps to efficiently transfer energy to ATP (reduces energy lost as heat) Three major pathways glycolysis (yields 2 ATP) glucose (6C) split into 2 pyruvic acid molecules (3C) aerobic respiration (yields ATP) completely oxidizes pyruvic acid to CO2 and H2O anaerobic fermentation (if no O2 available) pyruvic acid reduced to lactic acid replenishes NAD+ so glycolysis can continue

40 Overview of ATP Production

41 Coenzymes Capture energetic electrons from glucose during its catabolism coenzymes reduced gains energy (electron) charge reduced (electrons have negative charge) NAD+ (nicotinamide adenine dinucleotide) derived from niacin (B vitamin) NAD+ + H- + H+  NADH H+ FAD (flavin adenine dinucleotide) derived from riboflavin FAD + H- + H+  FADH2

42 Steps of Glycolysis (1) Phosphorylation Priming Cleavage
glucose enters cell has phosphate added - ATP used maintains favorable concentration gradient, prevents glucose from leaving cell Priming isomerization occurs phosphorylation further activates molecule - ATP used Cleavage molecule split into 2 three-carbon molecules

43 Steps of Glycolysis (2) Oxidation Dephosphorylation removes H+ and H-
NAD+ + H-  NADH Dephosphorylation transfers phosphate groups to ADP to form ATP 4 ATP produced (2 ATP used) for a net gain of 2 ATP produces pyruvic acid

44 Anaerobic Fermentation
Fate of pyruvic acid depends on oxygen availability In an exercising muscle, demand for ATP > oxygen supply; ATP produced by glycolysis glycolysis can not continue without supply of NAD+ NADH reduces pyruvic acid to lactic acid, restoring NAD+ Lactic acid travels to liver to be oxidized back to pyruvic when O2 is available (oxygen debt) then stored as glycogen or released as glucose Fermentation is inefficient, not favored by brain or heart

45 Aerobic Respiration Most ATP generated in mitochondria, require oxygen as final electron acceptor Principle steps matrix reactions occur in fluids of mitochondria membrane reactions whose enzymes are bound to the mitochondrial membrane

46 Mitochondrial Matrix Reactions
Three steps prepare pyruvic acid to enter citric acid cycle decarboxylation so that a 3-carbon becomes a 2-carbon compound convert that to an acetyl group (remove H) bind it to coenzyme A Known as formation of acetyl-coenzyme A

47 Mitochondrial Matrix Reactions

48 Mitochondrial Matrix Reactions
Citric Acid Cycle Acetyl-Co A (a C2 compound) combines with a C4 to form a C6 compound (citric acid)-- start of cycle Water is removed -- NAD+ is reduced to NADH -- CO2 is removed to form a C5 compound-- NAD+ is reduced to NADH -- CO2 is removed to form a C4 compound FAD is reduced to FADH2 -- water is added -- NAD+ is reduced to NADH Original C4 compound is reformed – ready to restart cycle

49 Summary of Matrix Reactions
2 pyruvate + 6H2O  6CO2 2 ADP + 2 Pi  2 ATP 8 NAD+ + 8 H H+  8 NADH + 8 H+ (2 NADH produced during formation of acetyl-CoA) 2 FAD + 2 H2  2 FADH2 Carbon atoms of glucose have all been carried away as CO2 and exhaled. Energy lost as heat, stored in 2 ATP, 8 reduced NADH, 2 FADH2 molecules of the matrix reactions and 2 NADH from glycolysis Citric acid cycle is a source of substances for synthesis of fats and nonessential amino acids

50 Membrane Reactions Purpose - to oxidize NADH and FADH2, transfer their energy to ATP and regenerate them Reactions carried out by series of compounds attached to inner mitochondrial membrane called electron transport chain FMN is derivative of riboflavin, iron-sulfur centers, Coenzyme Q, Copper ions bound to membrane proteins and cytochromes (5 enzymes with iron cofactors) As electrons are transferred along transport chain, their potential orbital energy is released Final electron acceptor is oxygen: accepts 2 electrons and 2 H+ to form a water molecule

51 Electron Transport Chain

52 Chemiosmotic Mechanism
Electron transport chain energy fuels enzyme complexes pump protons from matrix into space between inner and outer mitochondrial membranes creates steep electrochemical gradient for H+ across inner mitochondrial membrane Inner membrane is permeable to H+ at channel proteins called ATP synthase Chemiosmotic mechanism - H+ flow rushing back through these channels drives ATP synthesis

53 Chemiosmotic ATP Synthesis

54 Overview of ATP Production
NADH releases an electron pair to electron transport system and H+ to prime pumps enough energy to synthesize 3 ATP FADH2 releases its electron pairs further along electron-transport system enough energy to synthesize 2 ATP Complete aerobic oxidation of glucose to CO2 and H2O produces ATP efficiency rating of 40% -- rest is body heat

55 ATP Generated by Oxidation of Glucose

56 Glycogen Metabolism ATP is quickly used after it is formed -- it is not a storage molecule extra glucose will not be oxidized, it will be stored Glycogenesis -- synthesis of glycogen stimulated by insulin (average adult contains 450 g) Glycogenolysis -- glycogen  glucose stimulated by glucagon and epinephrine only liver cells can release glucose back into blood Gluconeogenesis -- synthesis of glucose from noncarbohydrates, such as fats and amino acids

57 Glucose Storage and Use

58 Lipids Triglycerides are stored in adipocytes
constant turnover of molecules every 3 weeks released into blood, transported and either oxidized or redeposited in other fat cells Lipogenesis = synthesizing fat from other sources amino acids and sugars used to make fatty acids and glycerol Lipolysis = breaking down fat for fuel glycerol is converted to PGAL and enters glycolysis fatty acids are broken down 2 carbons at a time to produce acetyl-CoA (beta oxidation)

59 Lipogenesis and Lipolysis Pathways

60 Ketogenesis Fatty acids catabolized into acetyl groups (by beta-oxidation in mitochondrial matrix) may enter citric acid cycle as acetyl-CoA undergo ketogenesis metabolized by liver to produce ketone bodies acetoacetic acid -hydroxybutyric acid acetone rapid or incomplete oxidization of fats raises blood ketone levels (ketosis) and may lead to a pH imbalance (ketoacidosis)

61 Proteins Amino acid pool - dietary amino acids plus 100 g of tissue protein broken down each day into free amino acids May be used to synthesize new proteins As fuel -- first must be deaminated (removal of NH2)--what remains is converted to pyruvic acid, acetyl-CoA or part of citric acid cycle during shortage of amino acids, the reverse occurs for protein synthesis the NH2 become ammonia (NH3) which is toxic and which the liver converts to urea (excreted in urine)

62 Pathways of Amino Acid Metabolism

63 Urea Synthesis Liver converts ammonia (NH3) to urea which is removed from blood by kidneys

64 Absorptive State Lasts about 4 hours during and after a meal
time of nutrient absorption and use for energy needs Carbohydrates blood glucose is available to all cells for ATP synthesis excess is converted by liver to glycogen or fat Fats taken up by fat cells from chylomicrons in the blood primary energy substrate for liver, fat and muscle cells Amino acids most pass through the liver and go onto other cells in liver cells, may be used for protein synthesis, used for fuel for ATP synthesis or used for fatty acid synthesis

65 Regulation of Absorptive State
Regulated by insulin secreted in response to elevated blood glucose and amino acid levels and the hormones gastrin, secretin and cholecystokinin Insulin increases the cellular uptake of glucose by 20-fold stimulates glucose oxidation, glycogenesis and lipogenesis but inhibits gluconeogenesis stimulates active transport of amino acids into cells and promotes protein synthesis high protein, low carbohydrate meals stimulate release of both insulin and glucagon preventing hypoglycemia

66 Postabsorptive State Homeostasis of blood glucose critical to brain
when stomach and small intestine are empty- stored fuels are used Carbohydrates glucose is drawn from glycogen reserves for up to 4 hours and then synthesized from other compounds Fat adipocytes and liver cells convert glycerol to glucose free fatty acids are oxidized by liver to ketone bodies other cells use for energy-- leaving glucose for brain Protein metabolism used as fuel when glycogen and fat reserves depleted wasting away occurs with cancer and other diseases from loss of appetite and altered metabolism

67 Regulation of Postabsorptive State
By sympathetic nervous system and glucagon Blood glucose drops, glucagon secreted glycogenolysis and gluconeogenesis raise glucose levels lipolysis raises free fatty acid levels

68 Regulation of Postabsorptive State
Sympathoadrenal effects promotes glycogenolysis and lipolysis under conditions of injury, fear, anger and stress adipose, liver cells and muscle cells are richly innervated and also respond to epinephrine from adrenal medulla Cortisol from adrenal cortex promotes  blood glucose fat and protein catabolism and gluconeogenesis Growth hormone – opposes rapid  in blood glucose

69 Metabolic Rate Amount of energy used in the body in a given period of time (kcal/hr or kcal/day) measured directly in calorimeter (water bath) measured indirectly by oxygen consumption Basal metabolic rate (BMR) relaxed, awake, fasting, room comfortable temperature adult male BMR is 2000 kcal/day(slightly less female) Factors affecting total MR pregnancy, anxiety, fever, eating, thyroid hormones, and depression

70 Body Heat and Thermoregulation
Homeostasis requires heat loss to match heat gain Hypothermia - excessively low body temperature can slow metabolic activity and cause death Hyperthermia - excessively high body temperature can disrupt enzymatic activity and metabolic activity and cause death Thermoregulation - ability to balance heat production and heat loss

71 Body Temperature “Normal” body temperature varies about 1.8 degrees F. in a 24-hour cycle low in morning and high in late afternoon Core body temperature is temperature of organs in cranial, thoracic and abdominal cavities rectal temperature is an estimate adult varies normally from degrees F. Shell temperature is temperature closer to the surface (oral cavity and skin) adult varies normally from degrees F.

72 Heat Production Comes from energy-releasing chemical reactions such as nutrient oxidation and ATP use From brain, heart, liver, endocrine and muscles exercise greatly  heat production in muscle

73 Modes of Heat Loss Radiation - loss of body heat to objects around us
caused by molecular motion producing infrared radiation Conduction - loss of body heat to the air which when warmed rises to be replaced by cooler air Evaporation - heat loss as sweat evaporates extreme conditions as much as 2L of sweat lost per hour, dissipating heat by as much as 600 kcal/hour

74 Thermoregulation Hypothalamic thermostat monitors temperature of blood and skin, signals heat-losing center to stimulate cutaneous vasodilation sweating signals heat-promoting center to stimulate cutaneous vasoconstriction arrector pili muscle contraction shivering thermogenesis (if needed) nonshivering thermogenesis -  thyroid hormone and BMR (seasonal adjustment) Behavioral thermoregulation get out of sun, remove heavy clothing

75 Disturbances of Thermoregulation
Fever normal protective mechanism that elevates BMR which produces more heat elevating the BMR, etc. Hyperthermia - exposure to excessive heat heat cramps are muscle spasms due to electrolyte imbalance from excessive sweating heat exhaustion -- severe electrolyte imbalance producing fainting, dizziness, hypotension heat stroke -- body temperature > 104 °F, may cause delirium, convulsions, coma, and death Hypothermia - exposure to excess cold as core body temperature , BMR  causing a further body temperature decrease, etc. (fatal if body temperature  75 °F)


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