Transcript ch24b_wcr
Chapter 24B Nutrition, Metabolism, Body Temperature Slides by Barbara Heard and W. Rose. figures from Marieb & Hoehn 9th ed. Portions copyright Pearson Education Protein Metabolism • Proteins deteriorate, so continually broken down and replaced • Amino acids recycled new proteins or different compound • Protein not stored in body – When dietary protein in excess, amino acids • Oxidized for energy • Converted to fat for storage © 2013 Pearson Education, Inc. Protein Synthesis • Amino acids most important anabolic nutrients – Form all proteins; bulk of functional molecules • Hormonally controlled • Requires complete set of amino acids – Essential amino acids required in diet • Synthesize 225 – 450 kg protein during lifetime © 2013 Pearson Education, Inc. Catabolic-Anabolic Steady State • Dynamic state in which – Organic molecules (except DNA) continuously broken down and rebuilt – Organs have different fuel preferences – Uses nutrient pools • Stores of amino acids, carbohydrates, fats © 2013 Pearson Education, Inc. Nutrient Pools • Three interconvertible pools – Amino acids – Carbohydrates – Fats • Amount and direction of conversion directed by liver, adipose tissue, skeletal muscle © 2013 Pearson Education, Inc. Amino Acid Pool • Body's total supply of free amino acids • Proteins lost in urine, hair, skin cells • Source for – Resynthesizing body proteins – Forming amino acid derivatives – Gluconeogenesis © 2013 Pearson Education, Inc. Carbohydrate and Fat Pools • Easily interconverted through key intermediates • Differ from amino acid pool – Fats and carbohydrates oxidized directly to produce energy; amino acids first converted to carbohydrate – Excess carbohydrate and fat can be stored; amino acids not stored as protein © 2013 Pearson Education, Inc. Figure 24.17 Interconversion of carbohydrates, fats, and proteins. Proteins Proteins Carbohydrates Glycogen Fats Triglycerides (neutral fats) Glucose Amino acids Glucose-6-phosphate Keto acids Glycerol and fatty acids Glyceraldehyde 3-phosphate Pyruvic acid Lactic acid Acetyl CoA Ketone bodies Urea Excreted in urine © 2013 Pearson Education, Inc. Krebs cycle Catabolic-Anabolic Steady State of the Body • Blood concentrations of energy sources equalized between absorptive state and postabsorptive state – Absorptive state during and 3-5 hours after each meal; absorption of nutrients occurring – Postabsorptive state late morning, late afternoon, all night; GI tract empty; energy sources supplied by breakdown of reserves © 2013 Pearson Education, Inc. Absorptive State • Anabolism exceeds catabolism • Nutrients stored • Carbohydrates – Glucose major cellular energy fuel – Glucose converted in liver to glycogen or fat • Synthesized fat + protein released to blood for storage by adipose tissue as very low density lipoproteins (VLDLs) © 2013 Pearson Education, Inc. Absorptive State • Triglycerides – Lipoprotein lipase catalyzes lipids of chylomicrons in muscle and fat tissues – Most glycerol and fatty acids converted to triglycerides for storage – Triglycerides used by adipose tissue, liver, and skeletal and cardiac muscle as primary energy source © 2013 Pearson Education, Inc. Absorptive State • Amino acids – Excess amino acids deaminated and used for ATP synthesis or stored as fat in liver – Most amino acids used in protein synthesis © 2013 Pearson Education, Inc. Figure 24.18a Major events and principal metabolic pathways of the absorptive state. Major metabolic thrust: anabolism and energy storage Amino acids Glucose Glycerol and fatty acids Major energy fuel: glucose (dietary) Glucose Liver metabolism: amino acids deaminated and used for energy or stored as fat Amino acids Keto acids Proteins Glycogen Triglycerides Triglycerides Major events of the absorptive state © 2013 Pearson Education, Inc. Figure 24.18b Major events and principal metabolic pathways of the absorptive state. In all tissues: In muscle: Glycogen Glucose Gastrointestinal tract Glucose Protein Glucose Amino acids In liver: Triglycerides Glycogen Keto acids Protein Fatty acids In adipose tissue: Glucose Glyceraldehyde 3-phosphate Glycerol Triglycerides Fatty acids Glycerol Fatty acids Triglycerides Principal pathways of the absorptive state © 2013 Pearson Education, Inc. Absorptive State: Hormonal Control • Absorptive state primarily controlled by insulin • Insulin secretion stimulated by – Elevated blood levels of glucose and amino acids – Intestinal GIP and parasympathetic stimulation © 2013 Pearson Education, Inc. Insulin Effects on Metabolism • Insulin, a hypoglycemic hormone, enhances – Facilitated diffusion of glucose into muscle and adipose cells (brain and liver take up glucose without insulin) – Glucose oxidation for energy – Glycogen and triglyceride formation – Active transport of amino acids into tissue cells – Protein synthesis – Inhibits glucose release from liver, and gluconeogenesis © 2013 Pearson Education, Inc. Homeostatic Imbalance • Diabetes mellitus – Inadequate insulin production or abnormal insulin receptors – Glucose unavailable to most body cells – Blood glucose levels high – Glucose lost in urine – Fats and proteins used for energy metabolic acidosis, protein wasting, weight loss © 2013 Pearson Education, Inc. Postabsorptive State • Catabolism of fat, glycogen, and proteins exceeds anabolism – Net synthesis of fat, glycogen, proteins ends • Goal - maintain blood glucose between meals – Makes glucose available to blood – Promotes use of fats for energy (glucose sparing – save glucose for organs that need it most) © 2013 Pearson Education, Inc. Sources of Blood Glucose • Glycogenolysis in liver • Glycogenolysis in skeletal muscle • Lipolysis in adipose tissues and liver – Glycerol used for gluconeogenesis in liver • Catabolism of cellular protein – Major source during prolonged fasting • Amount of fat in body determines how long can survive without food © 2013 Pearson Education, Inc. Figure 24.20a Major events and principal metabolic pathways of the postabsorptive state. Major metabolic thrust: catabolism and replacement of fuels in blood Proteins Glycogen Triglycerides Major energy fuels: glucose provided by glycogenolysis and gluconeogenesis; fatty acids, and ketones Glucose Fatty acids and ketones Liver metabolism: amino acids converted to glucose Amino acids Keto acids Amino acids Glucose Glycerol and fatty acids Glucose Major events of the postabsorptive state © 2013 Pearson Education, Inc. Figure 24.20b Major events and principal metabolic pathways of the postabsorptive state. In adipose tissue: Glycogen 2 In muscle: Protein 4 Triglycerides Pyruvic and lactic acids 3 Amino acids In most tissues: 4 2 Triglycerides 3 In liver: Glycerol Amino acids Pyruvic and lactic acids 4 Keto acids 3 2 Glucose Fatty acids + glycerol Fatty acids Ketone bodies Keto acids Blood glucose 1 Stored glycogen (b) In nervous tissue: Principal pathways of the postabsorptive state © 2013 Pearson Education, Inc. Postabsorptive State: Hormonal and Neural Controls • Glucagon - hyperglycemic hormone – Release stimulated by • Declining blood glucose • Rising amino acid levels © 2013 Pearson Education, Inc. Effects of Glucagon • Glucagon promotes – Glycogenolysis and gluconeogenesis in the liver – Lipolysis in adipose tissue fatty acids and glycerol to blood © 2013 Pearson Education, Inc. Postabsorptive State: Hormonal and Neural Controls • Adipose tissue innervated by sympathetic nervous system – Quickly supplies glucose if blood levels low – Low plasma glucose, fight-or-flight response, or exercise fat mobilization and glycogenolysis • Initiated by sympathetic nervous system and epinephrine from adrenal medulla © 2013 Pearson Education, Inc. Metabolic Role of the Liver • Hepatocytes – ~500 metabolic functions – Process nearly every class of nutrient – Play major role in regulating plasma cholesterol levels – Store vitamins and minerals – Metabolize alcohol, drugs, hormones, and bilirubin © 2013 Pearson Education, Inc. Cholesterol • Structural basis of bile salts, steroid hormones, and vitamin D • Major component of plasma membranes • 15% of blood cholesterol ingested; rest made in body, primarily liver • Lost from body when catabolized or secreted in bile salts • Part of hedgehog signaling molecule that directs embryonic development © 2013 Pearson Education, Inc. Cholesterol Transport • Lipoproteins – Transport water-insoluble cholesterol and triglycerides in blood – Regulate lipid entry/exit at target cells – Contain triglycerides, phospholipids, cholesterol, and protein • Higher percentage of lipids lower density, hence VLDLs, LDLs, HDLs © 2013 Pearson Education, Inc. Lipoproteins • Types of transport lipoproteins – HDLs (high-density lipoproteins) • Highest protein content – LDLs (low-density lipoproteins) • Cholesterol-rich – VLDLs (very low-density lipoproteins) • Mostly triglycerides – Chylomicrons • Lowest density © 2013 Pearson Education, Inc. Figure 24.22 Approximate composition of lipoproteins that transport lipids in body fluids. From intestine Made by liver 10% 20% Returned to liver 5% 30% 55–65% 80–95% 20% 45% 15–20% 45–50% 10–15% © 2013 Pearson Education, Inc. 25% 3–6% 2–7% 5–10% 1–2% Chylomicron VLDL Triglyceride Cholesterol Phospholipid Proteinl LDL HDL Lipoproteins • VLDLs – Transport triglycerides from liver to peripheral tissues (mostly adipose) • LDLs – Transport cholesterol to peripheral tissues for membranes, storage, or hormone synthesis • HDLs – Transport excess cholesterol from peripheral tissues to liver to be broken down and secreted into bile – Also provide cholesterol to steroid-producing organs © 2013 Pearson Education, Inc. Recommended Total Cholesterol, HDL, and LDL Levels • Total cholesterol = 200 mg/dl or less – Levels > 200 mg/dl linked to atherosclerosis • Form in which cholesterol transported in blood important to measure • High HDL thought to protect against heart disease; >60 good; <40 not good • High LDL cholesterol deposits in vessels; 100 or less good; 130 or above not good © 2013 Pearson Education, Inc. Plasma Cholesterol Levels • The liver produces cholesterol – At a basal level regardless of dietary cholesterol intake – In response to saturated fatty acids © 2013 Pearson Education, Inc. Plasma Cholesterol Levels • Ratio of saturated/unsaturated fatty acids affects blood cholesterol levels • Saturated fatty acids – Stimulate liver synthesis of cholesterol – Inhibit cholesterol excretion from body • Unsaturated fatty acids – Enhance excretion of cholesterol – Enhance cholesterol catabolism to bile salts © 2013 Pearson Education, Inc. Plasma Cholesterol Levels • Trans fats – Healthy oils forced to be solids • E.g., margarine – Worse effect on cholesterol levels than saturated fats – Increase LDLs and reduce HDLs © 2013 Pearson Education, Inc. Plasma Cholesterol Levels • Unsaturated omega-3 fatty acids (found in cold-water fish) – Lower proportions of saturated fats and cholesterol – Make platelets less sticky help prevent spontaneous clotting – Antiarrhythmic effects on heart – Lower blood pressure © 2013 Pearson Education, Inc. Non-Dietary Factors Affecting Cholesterol • Stress and cigarette smoking lower HDL levels • Aerobic exercise and estrogen increase HDL levels and decrease LDL levels © 2013 Pearson Education, Inc. Homeostatic Imbalance • Statins – Cholesterol-lowering drugs – Estimated >10 million Americans take statins © 2013 Pearson Education, Inc. Energy Balance • Bond energy released from food must equal total energy output • Energy intake = energy liberated during food oxidation • Energy output – Immediately lost as heat (~60%) – Used to do work (driven by ATP) – Stored as fat or glycogen © 2013 Pearson Education, Inc. Energy Balance • Nearly all energy from food eventually converted to heat - cannot be used to do work • Heat energy – Warms tissues and blood – Helps maintain homeostatic body temperature – Allows metabolic reactions to occur efficiently • If energy intake = energy output – weight stable • If not equal – gain or loss of weight © 2013 Pearson Education, Inc. Obesity • Body mass index (BMI) = W / H2 (W in kg, H in m) • Considered overweight if BMI 25 to 30 • Considered obese if BMI greater than 30 – Higher incidence of atherosclerosis, type 2 diabetes mellitus, hypertension, heart disease, and osteoarthritis • More adults and children overweight than 20 years ago © 2013 Pearson Education, Inc. Regulation of Food Intake • Various nuclei of hypothalamus – Release peptides influence feeding behavior • neuropeptide Y (NPY) enhances appetite • pro-opiomelanocortin (POMC) and cocaine/amphetamine-regulated transcript (CART) suppress appetite © 2013 Pearson Education, Inc. Regulation of Food Intake • Feeding behavior and hunger regulated by – – – – Neural signals from digestive tract Bloodborne signals related to body energy stores Hormones To lesser extent, body temperature and psychological factors • Operate through brain thermoreceptors, chemoreceptors, and others © 2013 Pearson Education, Inc. Short-Term Regulation of Food Intake • Neural signals from GI tract – High protein content of meal increases and prolongs afferent vagal signals – Distension sends signals along vagus nerve that suppress hunger center © 2013 Pearson Education, Inc. Short-Term Regulation of Food Intake • Nutrient signals related to energy stores – Increased nutrient levels in blood depress eating • Rising blood glucose • Elevated blood amino acid levels • Blood levels of fatty acids © 2013 Pearson Education, Inc. Short-Term Regulation of Food Intake • Hormones – Gut hormones (e.g., insulin and CCK) depress hunger – Glucagon and epinephrine stimulate hunger – Ghrelin (Ghr) from stomach stimulates appetite; levels peak prior to mealtime © 2013 Pearson Education, Inc. Long-Term Regulation of Food Intake • Leptin – Hormone secreted by fat cells in response to increased body fat mass – Indicator of total energy stores in fat tissue – Protects against weight loss in times of nutritional deprivation © 2013 Pearson Education, Inc. Long-Term Regulation of Food Intake • Leptin – Acts on certain neurons in hypothalamus – Suppresses secretion of NPY which is a potent appetite stimulant – Stimulates expression of appetite suppressants (e.g., CART peptides) © 2013 Pearson Education, Inc. Leptin • Rising leptin some weight loss; not "magic bullet" for obese patients • High leptin levels in obese patients; resistant to its action © 2013 Pearson Education, Inc. Additional Factors in Regulation of Food Intake • • • • • Temperature – cold activates hunger Stress – depends on individual Psychological factors Sleep deprivation Composition of gut bacteria © 2013 Pearson Education, Inc. Metabolic Rate and Heat Production • Metabolic rate – Total heat produced by chemical reactions and mechanical work of body – Can be measured • Directly – calorimeter measures heat liberated into water chamber • Indirectly – respirometer measures oxygen consumption (directly proportional to heat production) © 2013 Pearson Education, Inc. Basal Metabolic Rate • Reflects energy body needs to perform its most essential activities • Measured in postabsorptive state (npo 12 hours), reclining position, relaxed mentally and physically, room temperature 20-25C • Recorded as kilocalories per square meter of body surface per hour (kcal/m2/h) – E.g., 70 kg adult BMR = 66 kcal/h • Influenced by body surface area, age, gender, body temperature, stress, thyroxine © 2013 Pearson Education, Inc. Factors that Influence BMR • BMR increases as ratio of body surface area to volume increases • Decreases with age • Males have disproportionately higher BMR • Increases with temperature or stress • Thyroxine increases oxygen consumption, cellular respiration, and BMR • Physical training has little effect on BMR © 2013 Pearson Education, Inc. Metabolic Rate • Total metabolic rate (TMR) – Rate of kilocalorie consumption to fuel all ongoing activities – Increases with skeletal muscle activity and food ingestion (food-induced thermogenesis) • Greatest with protein and alcohol ingestion © 2013 Pearson Education, Inc. Regulation of Body Temperature • Body temperature reflects balance between heat production and heat loss • At rest, liver, heart, brain, kidneys, endocrine organs generate most heat • During exercise, heat production from skeletal muscles increases dramatically © 2013 Pearson Education, Inc. Regulation of Body Temperature • Normal body temperature = 37C 5C (98.6F) – Optimal enzyme activity at this temperature • Increased temperature denatures proteins and depresses neurons – Children <5 convulsions at 41C(106F) – ~43C (109F) - limit for life • Tissues tolerate low body temperatures © 2013 Pearson Education, Inc. Core and Shell Temperature • Core (organs within skull, thoracic & abdominal cavities) has highest temperature – Rectal temperature best clinical indicator • Core temperature regulated; fairly constant – Blood - major agent of heat exchange between core and shell • Shell (skin) – lowest temperature – Fluctuates between 20C – 40C © 2013 Pearson Education, Inc. Mechanisms of Heat Exchange • Four mechanisms of heat transfer – Radiation - loss of heat by infrared rays – Conduction - transfer of heat by direct contact – Convection - transfer of heat to surrounding air – Evaporation - heat loss due to evaporation of water from body surfaces • Heat absorbed by water during evaporation – heat of vaporization © 2013 Pearson Education, Inc. Mechanisms of Heat Exchange • Insensible heat loss accompanies insensible water loss from lungs, oral mucosa, and skin – Loss ~ 10% of basal heat production • Sensible heat loss – when body temperature rises and sweating increases water vaporization © 2013 Pearson Education, Inc. Role of the Hypothalamus • Hypothalamus receives afferent input from – Peripheral thermoreceptors in shell (skin) – Central thermoreceptors (some in hypothalamus) in core • Initiates appropriate heat-loss and heatpromoting activities © 2013 Pearson Education, Inc. Heat-Promoting Mechanisms • Constriction of cutaneous blood vessels – Sympathetic nervous system stimulates • Shivering – heat from skeletal muscle activity • Increased metabolic rate via epinephrine and norepinephrine – Chemical (nonshivering) thermogenesis infants – Brown adipose tissue in adults • Enhanced thyroxine release - infants © 2013 Pearson Education, Inc. Heat-Promoting Mechanisms • Behavioral modifications (voluntary) measures include – Putting on more clothing – Drinking hot fluids – Changing posture (clasping arms across chest) – Increasing physical activity (jumping up and down) © 2013 Pearson Education, Inc. Heat-Loss Mechanisms • • • • Heat-promoting center inhibited Dilation of cutaneous blood vessels Enhanced sweating Voluntary measures include – Reducing activity and seeking a cooler environment – Wearing light-colored, loose-fitting clothing © 2013 Pearson Education, Inc. Homeostatic Imbalance • Hyperthermia – Elevated body temperature depresses hypothalamus – Positive-feedback mechanism (heat stroke) begins at core temperature of 41C increased temperatures • Skin hot and dry; organs damaged – Can be fatal if not corrected © 2013 Pearson Education, Inc. Homeostatic Imbalance • Heat exhaustion – Heat-associated collapse after vigorous exercise – Due to dehydration and low blood pressure – Heat-loss mechanisms still functional – May progress to heat stroke if not cooled and rehydrated promptly © 2013 Pearson Education, Inc. Homeostatic Imbalance • Hypothermia – Low body temperature from cold exposure • Vital signs decrease – Shivering stops at core temperature of 30 - 32C – Can progress to coma and death by cardiac arrest at ~ 21C © 2013 Pearson Education, Inc. Fever • Controlled hyperthermia • Due to infection (also cancer, allergies, or CNS injuries) • Macrophages release cytokines (also called pyrogens) – Cause release of prostaglandins from hypothalamus © 2013 Pearson Education, Inc. Fever • Prostaglandins reset hypothalamic thermostat higher – heat-producing mechanisms – temperature rises • Natural body defenses or antibiotics reverse disease process – Cryogens (e.g., vasopressin) reset thermostat to lower (normal) level heat-loss mechanisms temperature falls © 2013 Pearson Education, Inc.