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Chapter 19

Chapter 19. Regulation of Metabolism. Nutritional Requirements. Living tissue is maintained by constant expenditure of energy (ATP). Indirectly from glucose, fatty acids, ketones, amino acids and other organic molecules. Energy of food is commonly measured in kilocalories.

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Chapter 19

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  1. Chapter 19 Regulation of Metabolism

  2. Nutritional Requirements • Living tissue is maintained by constant expenditure of energy (ATP). • Indirectly from glucose, fatty acids, ketones, amino acids and other organic molecules. • Energy of food is commonly measured in kilocalories. • One kilocalorie is = 1000 calories. • One calorie = amount of heat required to raise the temperature of 1 cm3 of H20 from 14.5o to 15.5o C.

  3. Metabolic Rate and Caloric Requirements • Metabolic rate measured by the amount of oxygen consumed by the body/min. • BMR: • Oxygen consumption of an awake relaxed person 12 – 14 hours after eating and at a comfortable temperature. • BMR determined by: • Age. • Gender. • Body surface area. • Thyroid secretion.

  4. Anabolism • Synthesis (build up): • Synthesize: • DNA and RNA. • Proteins. • Triglycerides. • Glycogen. • Must occur constantly to replace molecules that are hydrolyzed.

  5. Catabolism • Hydrolysis (break down): • Hydrolysis reactions and cellular respiration. • Gluconeogenesis. • Glycogenolysis. • Lipolysis.

  6. Turnover Rate • Rate at which a molecule is broken down and resynthesized. • Average daily turnover for carbohydrates is 250 g/day. • Only need about 150 g/day. • Average daily turnover for protein is 150 g/day. • Only need 35 g/day. • Average daily turnover for fats is 100 g/day. • Little is actually required in the diet.

  7. Vitamins and Minerals • Small organic molecules that serve as coenzymes in metabolic reactions or have highly specific functions. • Must be obtained from the diet because the body does not produce them, or does so in insufficient amounts. • Certain vitamins function as antioxidants. • 2 classes of vitamins: • Fat-soluble • Water-soluble

  8. Vitamins • Water-soluble vitamins: • Serve as coenzymes in the metabolism of carbohydrates, lipids, and proteins. • May serve as antioxidants. • Fat-soluble vitamins: • Serve as antioxidants. • Bind to nuclear receptors. • Involved in regulating fetal development. • Regulate Ca++ balance.

  9. Minerals • Needed as cofactors for specific enzymes and other critical functions. • Trace elements: • Required in small amounts from 50 mg to 18 mg/day.

  10. Free Radicals and Antioxidants • Electrons are located in orbitals. • Each orbital contains a maximum of 2 electrons. • Free radical: • When an orbital has an unpaired electron. • Highly reactive in the body. • Oxidize other atoms or reduce other atoms. • Major free radicals called: • Reactive oxygen or nitrogen species. • Oxygen or nitrogen as unpaired electron.

  11. Free Radicals and Antioxidants • Functions of free radicals: • Help to destroy bacteria. • Produce vasodilation. • NO, superoxide radical, and hydroxy radical. • Exert oxidative stress contributing to disease states. • Antioxidants: • Protective mechanism against oxidative stress. • Can react with free radicals by picking up unpaired electrons. • Glutathione, vitamin C, and vitamin E.

  12. Regulation of Energy Metabolism • Energy reserves: • Molecules that can be oxidized for energy are derived from storage molecules. • Circulating substrates: • Molecules absorbed through small intestine and carried to the cell.

  13. Regulatory Functions of Adipose Tissue • Adiposat: • Negative feedback loops to defend amount of adipose tissue. • Differentiation of adipocytes require nuclear receptor protein PPARg which is activated when bound to 15-D PGJ2. • Stimulate adipogenesis by promoting development of preadipocytes into mature adipocytes.

  14. Regulatory Functions of Adipose Tissue • Adipocytes secrete regulatory molecules. • Leptin: • Hormone that signals the hypothalamus to indicate the level of fat storage. • Satiety factor in obese have decreased sensitivity to leptin. • Neuropeptide Y is a potent stimulator of appetite. These neurons are inhibited by leptin. • TNFa: • Acts to reduce the sensitivity of cells to insulin. • Increased in obesity.

  15. Obesity • Obesity is often diagnosed by using using a body mass index (BMI). • BMI = w h 2 • W = weight in kilograms • H = height in meters • Obesity in childhood is due to an increase in both the size and the # of adipocytes. • Obesity defined as BMI > 30. • Healthy weight as BMI between 19 – 25.

  16. Hormonal Regulation of Metabolism • Absorptive state: • Absorption of energy. • 4 hour period after eating. • Increase in insulin secretion. • Postabsorptive state: • Fasting state. • At least 4 hours after the meal. • Increase in glucagon secretion.

  17. Balance Between Anabolism and Catabolism • The rate of deposit and withdrawl of energy substrates and the conversion of 1 type of energy substrate into another are regulated by hormones. • Antagonistic effects of insulin, glucagon, GH, T3, cortisol, and epinephrine balance anabolism and catabolism.

  18. Energy Regulation of Pancreas • Islets of Langerhans contain 3 distinct cell types: • a: glucagon. • b: insulin. • D: somatostatin.

  19. Regulation of Insulin and Glucagon • Mainly regulated by plasma [glucose]. • Lesser effect: plasma [amino acid]. • Regulated by negative feedback. • Glucose enters the brain by facilitated diffusion. • Normal fasting [glucose] is 65 – 105 mg/dl.

  20. Regulation of Insulin and Glucagon • Increased plasma [glucose]. • Glucose binds to GLUT2 receptor protein in b cells stimulating the production and release of insulin. • Insulin: • Stimulates skeletal muscle cells and adipocytes to incorporate GLUT4 (glucose facilitated diffusion carrier) into plasma membranes. • Promotes anabolism.

  21. Oral Glucose Tolerance Test • Measurement of the ability of beta cells to secrete insulin and ability of insulin to lower blood glucose.

  22. Regulation of Insulin and Glucagon • Parasympathetic Nervous System: • Stimulate insulin secretion. • Sympathetic Nervous System: • Stimulate glucagon secretion. • GIP: • Stimulate insulin secretion. • GLP-1: • Stimulate insulin secretion. • CCK: • Stimulate insulin secretion.

  23. Regulation of Insulin and Glucagon Secretion

  24. Absorptive State • Insulin is the major hormone that promotes anabolism in the body. • Plasma [insulin] increases. • Promotes cellular uptake of plasma glucose. • Stimulates glycogen storage in the liver and muscles. • Stimulates triglyceride storage in adipose cells. • Promotes cellular uptake of amino acids and synthesis of proteins.

  25. Postabsorptive State • Maintains plasma glucose concentration. • Plasma [glucagon] increased: • Stimulates glycogenolysis in the liver (glucose-6-phosphatase). • Stimulates gluconeogenesis. • Skeletal muscle, heart, liver and kidneys use fatty acids as major source of fuel (hormone-sensitive lipase).

  26. Diabetes Mellitus • Chronic high plasma [glucose]. • 2 forms of diabetes mellitus: • Type I: Insulin dependent diabetes (IDDM) • Type II: non-insulin dependent diabetes (NIDDM)

  27. Insulin-dependent Diabetes • b cells destroyed by autoimmune attack. • Killer T cells target glutamate decarboxylase in the beta cells. • Glucose cannot enter the adipose cells, rate of fat synthesis lags behind the rate of lipolysis. • Ketone production occurs, producing ketoacidosis. • Increased plasma [glucagon].

  28. Non-insulin Dependent Diabetes • Slow to develop. • Genetic factors are significant. • Occurs most often in people who are overweight. • Decreased sensitivity to insulin or an insulin resistance. • Obesity. • Do not usually develop ketoacidosis. • High plasma [insulin] or normal [insulin].

  29. Hypoglycemia • Oversecretion of insulin after a carbohydrate meal. • Caused by an exaggerated response to a rise in blood glucose. • Occurs in people who are genetically predisposed to type II diabetes.

  30. Metabolic Regulation • Anabolic effects of insulin are antagonized by the hormones of the adrenals, thyroid and growth hormones.

  31. Adrenal Medulla • Metabolic effects similar to glucagon. • Stimulate glycogenolysis. • Stimulate release of glucose from the liver. • Stimulate lipolysis and release of fatty acids. • NE stimulates b3 receptors in brown fat. • Contains uncoupling protein that dissociates electron transport from ATP production.

  32. Glucocorticoids • Release stimulated release of ACTH. • Supports the effects of increased glucagon. • Promotes lipolysis and ketogenesis. • Promotes protein breakdown in the muscles. • Promotes liver gluconeogenesis.

  33. Thyroxine • Active form is T3. • Stimulates cellular respiration by: • Production of uncoupling proteins. • Stimulate active transport Na+/ K+ pumps: • Lowers cellular [ATP] • Increases metabolic heat. • Increases metabolic rate.

  34. Growth Hormone • Somatotropin. • Inhibited by somatostatin. • Stimulates growth in children and adolescents. • Stimulated by: • GHRH. • Increase in plasma [amino acids]. • Decrease in plasma [glucose]. • Pulsitile, increasing during sleep, decreased during day.

  35. Growth Hormone • IGF-1: • Liver produces and secretes IGF-1 in response to GH. • Stimulates cell division and growth of cartilage. • IGF-2: • Has more insulin-like actions. • Promotes anabolism and catabolism. • Stimulates cellular uptake of amino acids. • Decreases glucose utilization by the tissues.

  36. Growth Hormone • Gigantism: • Excess GH secretion in children. • Acromegaly: • Excess GH secretion in adults after the epiphyseal discs are sealed. • Growth of soft tissue. • Dwarfism: • Inadequate secretion of GH during childhood.

  37. Regulation of Ca++ and Phosphate • Ca++ and phosphate concentrations are affected by: • Bone formation and resorption. • Intestinal absorption of Ca++ and P043- • Urinary excretion. • Osteoblasts: • Secrete an organic matrix. • Osteoclasts: • Secrete enzymes to dissolve hydroxyapatite. • Formation and resorption of bone occur constantly at rates determined by osteoblasts and osteoclasts.

  38. Parathyroid Hormone • PTH. • Single most important hormone in the control of plasma [Ca++]. • Stimulated by decreased plasma [Ca++]. • Stimulates osteoclasts to reabsorb bone. • Stimulates kidneys to reabsorb Ca++ from glomerular filtrate, and inhibit reabsorption of P043-. • Promotes formation of vitamin D3.

  39. Vitamin D3 • Directly stimulates intestinal absorption of Ca++ and P043-. • Directly stimulates bone reabsorption. • Kidney reabsorption of Ca++ and P043-. • Simultaneously raising Ca++ and P043- results in increased tendency of these 2 ions to precipitate as hydroxyapatite crystals.

  40. Vitamin D3 • Pre-vitamin D3is synthesized in the skin when exposed to mid-ultraviolet waves. • Pre-vitamin D3 isomerized to vitamin D3 (cholecalciferol). • Cholecalciferol is hydroxylated in liver to form 25 hydroxycholecalciferol. • In proximal convoluted tubule is hydroxylated to 1,25 dihydroxycholecalciferol (active vitamin D3).

  41. Calcitonin • Works with PTH and vitamin D3 to regulate plasma [Ca++]. • Stimulated by increased plasma [Ca++]. • Inhibits the activity of osteoclasts. • Stimulates urinary excretion of Ca++ and P043- by inhibiting reabsorption.

  42. Negative Feedback Control • Secretion of PTH, vitamin D3, and calcitonin influenced by plasma [Ca++].

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