Regulation Of Metabolism


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Regulation Of Metabolism

  1. 1. Chapter 19 Regulation of Metabolism
  2. 2. Nutritional Requirements <ul><li>Living tissue is maintained by constant expenditure of energy (ATP). </li></ul><ul><ul><li>Indirectly from glucose, fatty acids, ketones, amino acids, and other organic molecules . </li></ul></ul><ul><li>Energy of food is commonly measured in kilocalories. </li></ul><ul><ul><li>One kilocalorie is = 1000 calories. </li></ul></ul><ul><li>One calorie = amount of heat required to raise the temperature of 1 cm 3 of H 2 0 from 14.5 o to 15.5 o C. </li></ul><ul><ul><li>The amount of energy released as heat when food is combusted in vitro = amount of energy released within cells through aerobic respiration. </li></ul></ul>
  3. 3. Metabolic Rate and Caloric Requirements <ul><li>Metabolic rate is the total rate of body metabolism. </li></ul><ul><ul><li>Metabolic rate measured by the amount of oxygen consumed by the body/min. </li></ul></ul><ul><li>BMR: </li></ul><ul><ul><li>Oxygen consumption of an awake relaxed person 12–14 hours after eating and at a comfortable temperature. </li></ul></ul><ul><li>BMR determined by: </li></ul><ul><ul><li>Age. </li></ul></ul><ul><ul><li>Gender. </li></ul></ul><ul><ul><li>Body surface area. </li></ul></ul><ul><ul><li>Thyroid secretion. </li></ul></ul>
  4. 4. Anabolic Requirements <ul><li>Anabolism: </li></ul><ul><ul><li>Food supplies raw materials for synthesis reactions. </li></ul></ul><ul><li>Synthesize: </li></ul><ul><ul><li>DNA and RNA. </li></ul></ul><ul><ul><li>Proteins. </li></ul></ul><ul><ul><li>Triglycerides. </li></ul></ul><ul><ul><li>Glycogen. </li></ul></ul><ul><li>Must occur constantly to replace molecules that are hydrolyzed. </li></ul>
  5. 5. Aerobic Requirements (continued) <ul><li>Catabolism: </li></ul><ul><ul><li>Hydrolysis (break down monomers down to C0 2 and H 2 0.): </li></ul></ul><ul><ul><ul><li>Hydrolysis reactions and cellular respiration. </li></ul></ul></ul><ul><ul><ul><li>Gluconeogenesis. </li></ul></ul></ul><ul><ul><ul><li>Glycogenolysis. </li></ul></ul></ul><ul><ul><ul><li>Lipolysis. </li></ul></ul></ul>
  6. 6. Turnover Rate <ul><li>Rate at which a molecule is broken down and resynthesized. </li></ul><ul><li>Average daily turnover for carbohydrates is 250 g/day. </li></ul><ul><ul><li>Some glucose is reused to form glycogen. </li></ul></ul><ul><ul><ul><li>Only need about 150 g/day. </li></ul></ul></ul><ul><li>Average daily turnover for protein is 150 g/day. </li></ul><ul><ul><li>Some protein may be reused for protein synthesis. </li></ul></ul><ul><ul><ul><li>Only need 35 g/day. </li></ul></ul></ul><ul><ul><ul><ul><li>9 essential amino acids. </li></ul></ul></ul></ul><ul><li>Average daily turnover for fats is 100 g/day. </li></ul><ul><ul><li>Little is actually required in the diet. </li></ul></ul><ul><ul><ul><li>Fat can be produced from excess carbohydrates. </li></ul></ul></ul><ul><ul><ul><ul><li>Essential fatty acids: </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Linoleic and linolenic acids. </li></ul></ul></ul></ul></ul>
  7. 7. Vitamins and Minerals <ul><li>Vitamins: </li></ul><ul><ul><li>Small organic molecules that serve as coenzymes in metabolic reactions or have highly specific functions. </li></ul></ul><ul><li>Must be obtained from the diet because the body does not produce them, or does so in insufficient amounts. </li></ul><ul><li>2 classes of vitamins: </li></ul><ul><ul><li>Fat-soluble: </li></ul></ul><ul><ul><ul><li>A,D, E, and K. </li></ul></ul></ul><ul><ul><li>Water-soluble: </li></ul></ul><ul><ul><ul><li>B 1 , B 2 , B 3 , B 6 , B 12 , pantothenic acid, biotin, folic acid, and vitamin C. </li></ul></ul></ul>
  8. 8. Vitamins <ul><li>Water-soluble vitamins: </li></ul><ul><ul><li>Serve as coenzymes in the metabolism of carbohydrates, lipids, and proteins. </li></ul></ul><ul><ul><li>May serve as antioxidants. </li></ul></ul><ul><li>Fat-soluble vitamins: </li></ul><ul><ul><li>Bind to nuclear receptors. </li></ul></ul><ul><ul><li>Serve as antioxidants. </li></ul></ul><ul><ul><li>Assist in regulation of fetal development. </li></ul></ul><ul><ul><li>Regulate Ca 2+ balance. </li></ul></ul>
  9. 9. The Major Vitamins
  10. 10. Minerals <ul><li>Needed as cofactors for specific enzymes and other critical functions. </li></ul><ul><li>Trace elements: </li></ul><ul><ul><li>Required in small amounts from 50  g to 18 mg/day. </li></ul></ul>
  11. 11. Free Radicals and Antioxidants <ul><li>Electrons are located in orbitals. </li></ul><ul><ul><li>Each orbital contains a maximum of 2 electrons. </li></ul></ul><ul><li>Free radical: </li></ul><ul><ul><li>When an orbital has an unpaired electron. </li></ul></ul><ul><ul><li>Highly reactive in the body. </li></ul></ul><ul><ul><li>Oxidize or reduce other atoms. </li></ul></ul><ul><li>Major free radicals called: </li></ul><ul><ul><li>Reactive oxygen or nitrogen species: </li></ul></ul><ul><ul><ul><li>Oxygen or nitrogen as unpaired electron. </li></ul></ul></ul>
  12. 12. Free Radicals and Antioxidants (continued) <ul><li>Functions of free radicals: </li></ul><ul><ul><li>Help to destroy bacteria. </li></ul></ul><ul><ul><li>Produce vasodilation. </li></ul></ul><ul><ul><ul><li>NO radical, superoxide radical, and hydroxy radical. </li></ul></ul></ul><ul><li>Exert oxidative stress contributing to disease states. </li></ul><ul><ul><li>Excess production of free radicals can damage lipids, proteins, and DNA. </li></ul></ul><ul><ul><li>Promotes apoptosis, contributes to aging, inflammatory disease, heart disease, CVA, HTN, and degenerative disease. </li></ul></ul><ul><ul><li>Promotes malignant growth. </li></ul></ul><ul><li>Protective mechanism against oxidative stress. </li></ul><ul><ul><li>Can react with free radicals by picking up unpaired electrons. </li></ul></ul><ul><ul><ul><li>Glutathione, vitamin C, and vitamin E. </li></ul></ul></ul>
  13. 13. Reactive Oxygen Species <ul><li>Insert fig. 19.1 </li></ul>
  14. 14. Regulation of Energy Metabolism <ul><li>Energy reserves: </li></ul><ul><ul><li>Molecules that can be oxidized for energy are derived from storage molecules (glycogen, protein, and fat). </li></ul></ul><ul><li>Circulating substrates: </li></ul><ul><ul><li>Molecules absorbed through small intestine and carried to the cell for use in cell respiration. </li></ul></ul>Insert fig. 19.2
  15. 15. Eating <ul><li>Eating behaviors partially controlled by hypothalamus. </li></ul><ul><li>Lesions in vetromedial area produce hyperphagia (obesity). </li></ul><ul><li>Lesions in lateral hypothalamus produces hypophagia (weight loss). </li></ul><ul><li>Endorphins, NE, serotonin, and CCK affect hunger and satiety. </li></ul>
  16. 16. Regulatory Functions of Adipose Tissue <ul><li>Adipostat regulatory system (negative feedback loops) to defend amount of adipose tissue. </li></ul><ul><ul><li>Differentiation of adipocytes require nuclear receptor protein (PPAR  which is activated when bound to 15-D PGJ 2: </li></ul></ul><ul><ul><ul><li>Stimulates adipogenesis by promoting development of preadipocytes into mature adipocytes. </li></ul></ul></ul><ul><ul><li>Number of adipocytes increase after birth. </li></ul></ul><ul><ul><ul><li>Differentiation promoted by high [fatty acids]. </li></ul></ul></ul><ul><li>Adipocytes store fat within large vacuoles. </li></ul><ul><ul><li>May secrete hormones involved in regulation of metabolism. </li></ul></ul>
  17. 17. Regulatory Functions of Adipose Tissue (continued) <ul><ul><li>Leptin: </li></ul></ul><ul><ul><ul><li>Hormone that signals the hypothalamus to indicate the level of fat storage. </li></ul></ul></ul><ul><ul><ul><li>Involved in long-term regulation of eating. </li></ul></ul></ul><ul><ul><ul><ul><li>Satiety factor in obese have decreased sensitivity to leptin in the brain. </li></ul></ul></ul></ul><ul><ul><li>Neuropeptide Y: </li></ul></ul><ul><ul><ul><li>Potent stimulator of appetite. </li></ul></ul></ul><ul><ul><ul><li>Functions as a NT within the hypothalamus. </li></ul></ul></ul><ul><ul><ul><ul><li>These neurons are inhibited by leptin. </li></ul></ul></ul></ul><ul><ul><li>TNF  </li></ul></ul><ul><ul><ul><li>Acts to reduce the sensitivity of cells to insulin. </li></ul></ul></ul><ul><ul><ul><ul><li>Increased in obesity. </li></ul></ul></ul></ul><ul><ul><ul><li>May contribute to insulin resistance. </li></ul></ul></ul>
  18. 18. Regulation of Hunger <ul><li>Adipose tissue secrete satiety factor: </li></ul><ul><ul><li>Acts through its regulation of hunger centers in hypothalamus. </li></ul></ul><ul><li>Ghrelin: </li></ul><ul><ul><li>Secreted by stomach. </li></ul></ul><ul><ul><ul><li>Secretions rise between meals and stimulate hunger. </li></ul></ul></ul><ul><li>CCK: </li></ul><ul><ul><li>Secretions rise during and immediately after a meal. </li></ul></ul><ul><ul><ul><li>Produce satiety. </li></ul></ul></ul><ul><li>PYY 3-36 : </li></ul><ul><ul><li>Acts within the hypothalamus. </li></ul></ul><ul><ul><ul><li>Decreases neuropeptide Y. </li></ul></ul></ul>
  19. 19. Obesity <ul><li>Obesity is often diagnosed by using using a body mass index (BMI). </li></ul><ul><li>BMI = w h 2 </li></ul><ul><ul><ul><li>w = weight in kilograms </li></ul></ul></ul><ul><ul><ul><li>h = height in meters </li></ul></ul></ul><ul><li>Healthy weight as BMI between 19 – 25. </li></ul><ul><li>Obesity defined as BMI > 30. </li></ul><ul><ul><li>Obesity in childhood is due to an increase in both the size and the # of adipocytes. </li></ul></ul><ul><ul><li>Weight gains in adulthood is due to increase in adipocyte size in intra-abdominal fat. </li></ul></ul>
  20. 20. Calorie Expenditures <ul><li>3 components: </li></ul><ul><ul><li>Basal metabolic rate (BMR): </li></ul></ul><ul><ul><ul><li>60% total calorie expenditure. </li></ul></ul></ul><ul><ul><li>Adaptive thermogenesis: </li></ul></ul><ul><ul><ul><li>10% total calorie expenditure. </li></ul></ul></ul><ul><ul><li>Physical activity: </li></ul></ul><ul><ul><ul><li>Contribution variable. </li></ul></ul></ul>
  21. 21. Hormonal Regulation of Metabolism <ul><li>Absorptive state: </li></ul><ul><ul><li>Absorption of energy. </li></ul></ul><ul><ul><li>4 hour period after eating. </li></ul></ul><ul><ul><li>Increase in insulin secretion. </li></ul></ul><ul><li>Postabsorptive state: </li></ul><ul><ul><li>Fasting state. </li></ul></ul><ul><ul><li>At least 4 hours after the meal. </li></ul></ul><ul><ul><li>Increase in glucagon secretion. </li></ul></ul>
  22. 22. Balance Between Anabolism and Catabolism <ul><li>The rate of deposit and withdrawal of energy substrates, and the conversion of 1 type of energy substrate into another; are regulated by hormones. </li></ul><ul><li>Antagonistic effects of insulin, glucagon, GH, T 3 , cortisol, and Epi balance anabolism and catabolism. </li></ul>Insert fig. 19.4
  23. 23. Energy Regulation of Pancreas <ul><li>Islets of Langerhans contain 3 distinct cell types: </li></ul><ul><ul><li> cells  </li></ul></ul><ul><ul><ul><li>Secrete  glucagon. </li></ul></ul></ul><ul><ul><li> cells  </li></ul></ul><ul><ul><ul><li>Secrete  insulin. </li></ul></ul></ul><ul><ul><li> cells  </li></ul></ul><ul><ul><ul><li>Secrete somatostatin.  </li></ul></ul></ul><ul><li> </li></ul>
  24. 24. Regulation of Insulin and Glucagon <ul><li>Mainly regulated by blood [glucose]. </li></ul><ul><li>Lesser effect: blood [amino acid]. </li></ul><ul><ul><li>Regulated by negative feedback. </li></ul></ul><ul><li>Glucose enters the brain by facilitated diffusion. </li></ul><ul><li>Normal fasting [glucose] is 65–105 mg/dl. </li></ul>
  25. 25. Regulation of Insulin and Glucagon (continued) <ul><li>When blood [glucose] increases: </li></ul><ul><ul><li>Glucose binds to GLUT2 receptor protein in  cells, stimulating the production and release of insulin. </li></ul></ul><ul><li>Insulin: </li></ul><ul><ul><li>Stimulates skeletal muscle cells and adipocytes to incorporate GLUT4 (glucose facilitated diffusion carrier) into plasma membranes. </li></ul></ul><ul><ul><ul><li>Promotes anabolism. </li></ul></ul></ul>
  26. 26. Oral Glucose Tolerance Test <ul><li>Measurement of the ability of  cells to secrete insulin. </li></ul><ul><li>Ability of insulin to lower blood glucose. </li></ul><ul><li>Normal person’s rise in blood [glucose] after drinking solution is reversed to normal in 2 hrs. </li></ul>Insert fig. 19.8
  27. 27. Regulation of Insulin and Glucagon <ul><li>Parasympathetic nervous system: </li></ul><ul><ul><li>Stimulates insulin secretion. </li></ul></ul><ul><li>Sympathetic nervous system: </li></ul><ul><ul><li>Stimulates glucagon secretion. </li></ul></ul><ul><li>GIP: </li></ul><ul><ul><li>Stimulates insulin secretion. </li></ul></ul><ul><li>GLP-1: </li></ul><ul><ul><li>Stimulates insulin secretion. </li></ul></ul><ul><li>CCK: </li></ul><ul><ul><li>Stimulates insulin secretion. </li></ul></ul>
  28. 28. Regulation of Insulin and Glucagon Secretion (continued)
  29. 29. Absorptive State <ul><li>Insulin is the major hormone that promotes anabolism in the body. </li></ul><ul><li>When blood [insulin] increases: </li></ul><ul><ul><li>Promotes cellular uptake of glucose. </li></ul></ul><ul><ul><li>Stimulates glycogen storage in the liver and muscles. </li></ul></ul><ul><ul><li>Stimulates triglyceride storage in adipose cells. </li></ul></ul><ul><ul><li>Promotes cellular uptake of amino acids and synthesis of proteins. </li></ul></ul>
  30. 30. Postabsorptive State <ul><li>Maintains blood glucose concentration. </li></ul><ul><li>When blood [glucagon] increased: </li></ul><ul><ul><li>Stimulates glycogenolysis in the liver (glucose-6-phosphatase). </li></ul></ul><ul><ul><li>Stimulates gluconeogenesis. </li></ul></ul><ul><ul><li>Skeletal muscle, heart, liver, and kidneys use fatty acids as major source of fuel (hormone-sensitive lipase). </li></ul></ul><ul><ul><li>Stimulates lipolysis and ketogenesis. </li></ul></ul>
  31. 31. Effect of Feeding and Fasting on Metabolism Insert fig. 19.10
  32. 32. Diabetes Mellitus <ul><li>Chronic high blood [glucose]. </li></ul><ul><li>2 forms of diabetes mellitus: </li></ul><ul><ul><li>Type I: insulin dependent diabetes (IDDM). </li></ul></ul><ul><ul><li>Type II: non-insulin dependent diabetes (NIDDM). </li></ul></ul>
  33. 33. Comparison of Type I and Type II Diabetes Mellitus Insert table 19.6
  34. 34. Type I Diabetes Mellitus <ul><li> cells of the islets of Langerhans are destroyed by autoimmune attack which may be provoked by environmental agent. </li></ul><ul><ul><li>Killer T cells target glutamate decarboxylase in the  cells. </li></ul></ul><ul><li>Glucose cannot enter the adipose cells. </li></ul><ul><ul><li>Rate of fat synthesis lags behind the rate of lipolysis. </li></ul></ul><ul><ul><ul><li>Fatty acids converted to ketone bodies, producing ketoacidosis. </li></ul></ul></ul><ul><li>Increased blood [glucagon]. </li></ul><ul><ul><li>Stimulates glycogenolysis in liver. </li></ul></ul>
  35. 35. Consequences of Uncorrected Deficiency in Type I Diabetes Mellitus Insert fig. 19.11
  36. 36. Type II Diabetes Mellitus <ul><li>Slow to develop. </li></ul><ul><li>Genetic factors are significant. </li></ul><ul><li>Occurs most often in people who are overweight. </li></ul><ul><li>Decreased sensitivity to insulin or an insulin resistance. </li></ul><ul><ul><li>Obesity. </li></ul></ul><ul><li>Do not usually develop ketoacidosis. </li></ul><ul><li>May have high blood [insulin] or normal [insulin]. </li></ul>Insert fig. 19.12
  37. 37. Treatment in Diabetes <ul><li>Change in lifestyle: </li></ul><ul><ul><li>Increase exercise: </li></ul></ul><ul><ul><ul><li>Increases the amount of membrane GLUT-4 carriers in the skeletal muscle cells. </li></ul></ul></ul><ul><ul><li>Weight reduction. </li></ul></ul><ul><ul><li>Increased fiber in diet. </li></ul></ul><ul><ul><li>Reduce saturated fat. </li></ul></ul>
  38. 38. Hypoglycemia <ul><li>Over secretion of insulin. </li></ul><ul><li>Reactive hypoglycemia: </li></ul><ul><ul><li>Caused by an exaggerated response to a rise in blood glucose. </li></ul></ul><ul><ul><li>Occurs in people who are genetically predisposed to type II diabetes. </li></ul></ul>Insert fig. 19.13
  39. 39. Metabolic Regulation <ul><li>Anabolic effects of insulin are antagonized by the hormones of the adrenals, thyroid, and anterior pituitary. </li></ul><ul><ul><li>Insulin, T 3 , and GH can act synergistically to stimulate protein synthesis. </li></ul></ul>
  40. 40. Metabolic Effects of Catecholamines <ul><li>Metabolic effects similar to glucagon. </li></ul><ul><li>Stimulate glycogenolysis. </li></ul><ul><ul><li>Stimulate release of glucose from the liver. </li></ul></ul><ul><ul><li>Stimulate lipolysis and release of fatty acids. </li></ul></ul><ul><li>NE stimulates  3 receptors in brown fat. </li></ul><ul><ul><li>Contains uncoupling protein that dissociates electron transport from ATP production. </li></ul></ul>
  41. 41. Metabolic Effects of Catecholamines (continued)
  42. 42. Metabolic Effects of Glucocorticoids <ul><li>Glucocorticoids secreted in response to release of ACTH. </li></ul><ul><li>Support the effects of increased glucagon. </li></ul><ul><li>Promote lipolysis and ketogenesis. </li></ul><ul><li>Promote protein breakdown in the muscles. </li></ul><ul><ul><li>Increases blood [amino acids]. </li></ul></ul><ul><li>Promote liver gluconeogenesis. </li></ul>
  43. 43. Thyroxine <ul><li>Active form is T 3 . </li></ul><ul><li>Stimulates cellular respiration by: </li></ul><ul><ul><li>Production of uncoupling proteins. </li></ul></ul><ul><li>Stimulation of active transport Na + /K + pumps: </li></ul><ul><ul><li>Lowers cellular [ATP]. </li></ul></ul><ul><li>Increases metabolic heat. </li></ul><ul><li>Increases metabolic rate. </li></ul><ul><li>Contributes to proper growth and development of CNS in children. </li></ul>
  44. 44. Growth Hormone (Somatotropin) <ul><li>Inhibited by somatostatin. </li></ul><ul><li>Stimulates growth in children and adolescents. </li></ul><ul><li>Stimulated by: </li></ul><ul><ul><li>GHRH. </li></ul></ul><ul><ul><li>Increase in blood [amino acids]. </li></ul></ul><ul><ul><li>Decrease in blood [glucose]. </li></ul></ul><ul><li>Pulsatile, increasing during sleep, decreasing during day. </li></ul>
  45. 45. Growth Hormone (continued) <ul><li>IGF-1: </li></ul><ul><ul><li>Liver produces and secretes IGF-1 in response to GH. </li></ul></ul><ul><ul><li>Stimulates cell division and growth of cartilage. </li></ul></ul><ul><li>IGF-2: </li></ul><ul><ul><li>Has more insulin-like actions. </li></ul></ul><ul><li>Promotes anabolism and catabolism. </li></ul><ul><ul><li>Stimulates cellular uptake of amino acids and protein synthesis. </li></ul></ul><ul><ul><li>Decreases glucose utilization by the tissues. </li></ul></ul><ul><ul><ul><li>Raises blood [glucose]. </li></ul></ul></ul>
  46. 46. Effects of Growth Hormone on Body Growth <ul><li>Gigantism: </li></ul><ul><ul><li>Excess GH secretion in children. </li></ul></ul><ul><ul><ul><li>Maintain normal body proportions. </li></ul></ul></ul><ul><li>Acromegaly: </li></ul><ul><ul><li>Excess GH secretion in adults after the epiphyseal discs are sealed. </li></ul></ul><ul><ul><ul><li>No increase in height. </li></ul></ul></ul><ul><ul><li>Growth of soft tissue. </li></ul></ul><ul><ul><ul><li>Elongation of jaw, deformities in hands, feet, and bones of face. </li></ul></ul></ul><ul><li>Dwarfism: </li></ul><ul><ul><li>Inadequate secretion of GH during childhood. </li></ul></ul>
  47. 47. Progression of Acromegaly
  48. 48. Bone Deposition and Resorption <ul><li>Ca 2+ and phosphate concentrations are affected by: </li></ul><ul><ul><li>Bone formation and resorption. </li></ul></ul><ul><ul><li>Intestinal absorption of Ca 2+ and P0 4 3- . </li></ul></ul><ul><ul><li>Urinary excretion. </li></ul></ul><ul><li>Osteoblasts: </li></ul><ul><ul><li>Secrete an organic matrix of collagen proteins. </li></ul></ul><ul><ul><li>Deposit hydroxyapatite crystals. </li></ul></ul><ul><li>Osteoclasts: </li></ul><ul><ul><li>Secrete enzymes to dissolve hydroxyapatite. </li></ul></ul><ul><li>Formation and resorption of bone occur constantly at rates determined by osteoblasts and osteoclasts. </li></ul>
  49. 49. Bone Deposition and Resorption (continued) <ul><li>Bone resorption occurs when an osteoclast attaches to the bone matrix and forms ruffled membrane. </li></ul><ul><li>Osteoclast secretes products that dissolve both Ca 2+ and P0 4 3- ; and digest the matrix. </li></ul><ul><ul><li>Transport of H + by H + ATPase pump in ruffled border. </li></ul></ul><ul><ul><li>Cl - channel allows Cl - to flow to H + to maintain electrical neutrality. </li></ul></ul><ul><li>Protein matrix digested by cathepsin K. </li></ul><ul><ul><li>Cytoplasm prevented from becoming to basic by a Cl - /HC0 3 - pump. </li></ul></ul>
  50. 50. Bone Deposition and Resorption (continued)
  51. 51. Parathyroid Hormone (PTH) <ul><li>Single most important hormone in the control of blood [Ca 2+ ]. </li></ul><ul><ul><li>Stimulated by decreased blood [Ca 2+ ]. </li></ul></ul><ul><li>Stimulates osteoclasts to reabsorb bone. </li></ul><ul><li>Stimulates kidneys to reabsorb Ca 2+ from glomerular filtrate, and inhibit reabsorption of P0 4 3- . </li></ul><ul><li>Promotes formation of 1,25 vitamin D 3 . </li></ul><ul><li>Many cancers secrete PTH-related protein that interacts with PTH receptors. </li></ul><ul><ul><li>Produce hypercalcemia. </li></ul></ul>
  52. 52. Calcitonin <ul><li>Works with PTH and 1,25 vitamin D 3 to regulate blood [Ca 2+ ]. </li></ul><ul><li>Stimulated by increased plasma [Ca 2+ ]. </li></ul><ul><li>Inhibits the activity of osteoclasts. </li></ul><ul><li>Stimulates urinary excretion of Ca 2+ and P0 4 3- by inhibiting reabsorption. </li></ul><ul><li>Physiological significance in adults is questionable. </li></ul>
  53. 53. 1,25 Vitamin D 3 <ul><li>Pre-vitamin D 3 is synthesized in the skin when exposed to mid-ultraviolet waves. </li></ul><ul><ul><li>Pre-vitamin D 3 isomerized to vitamin D 3 (cholecalciferol). </li></ul></ul><ul><li>Cholecalciferol is hydroxylated in liver to form 25 hydroxycholecalciferol. </li></ul><ul><li>In proximal convoluted tubule is hydroxylated to 1,25 dihydroxycholecalciferol (active vitamin D 3 ). </li></ul><ul><ul><li>Stimulated by PTH. </li></ul></ul>
  54. 54. Production of 1,25 dihydroxyvitamin D 3 Insert fig. 19.20
  55. 55. 1,25 dihydroxyvitamin D 3 (continued) <ul><li>Directly stimulates intestinal absorption of Ca 2+ and P0 4 3- . </li></ul><ul><li>When Ca 2+ intake is inadequate, directly stimulates bone reabsorption. </li></ul><ul><li>Stimulates reabsorption of Ca 2+ and P0 4 3- by the kidney. </li></ul><ul><ul><li>Simultaneously raising Ca 2+ and P0 4 3- results in increased tendency of these 2 ions to precipitate as hydroxyapatite crystals. </li></ul></ul><ul><li>Stimulated by PTH. </li></ul>
  56. 56. Negative Feedback Control Insert fig. 19.23