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Metabolism

Metabolism. Chapter 25 - pages 962-987. Linking anabolism & catabolism. Topics in Chapter 25. In A&P I glucose catabolism  ATP was discussed This semester in Ch 25 focus on: Glucose anabolism Lipid metabolism Protein metabolism Metabolism during absorptive and post absorptive states

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Metabolism

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  1. Metabolism Chapter 25 - pages 962-987

  2. Linking anabolism & catabolism

  3. Topics in Chapter 25 • In A&P I glucose catabolism  ATP was discussed • This semester in Ch 25 focus on: • Glucose anabolism • Lipid metabolism • Protein metabolism • Metabolism during absorptive and post absorptive states • Heat and energy balance • Nutrition

  4. Glucose • Most glucose catabolized to make ATP • Some used in anabolic rxns: • To produce glycogen • To produce more glucose from lipid and protein components

  5. Do not confuse these terms! • Glucose • Glycogen • Glucagon • Glycolysis • Glycogenolysis • Glycogenesis • Gluconeogenesis

  6. Glycogenesis fig 25.11 • Glucose storage • Occurs when glucose not immediately needed for ATP synthesis • _____________- stimulates hepatocytes & skeletal muscle cells to carry out • From pancreatic beta cells • ______________ - polysaccharide, polymer of glucose and only stored carb in our body • 75% stored in skeletal muscle • 25% in hepatocytes

  7. Glycogenolysis fig 25.11 • Glucose release • Body activities require ATP  glycogen stores in hepatocytes break down • Glucose  blood  cells for catabolism • Glucose  ATP • Lactic acid (in muscle)  glucose (in liver) • Phosphorylase activated by ____________ (from pancreatic alpha cells) & ___________ (adrenal medulla) • Reversal of steps in glycogenesis

  8. Glycogenesis & glycogenolysis

  9. Insulin pg 646-649 • Released in response to  blood glucose • Ach released from vagus nerve  _________________ • Certain amino acids in blood (after protein meal) • ________ – s.i. hormone released due to glucose in gi tract • Accelerates facilitated diffusion of glucose •  glycogenesis (glucose  glycogen) •  a.a uptake for  protein synthesis •  f.a. synthesis • Slows glycogenolysis • Slows gluconeogenesis

  10. Fig 18.18

  11. Figure 18.19

  12. Glucagon • Stimulates ________________ in liver cells • Stimulates ________________ • Glucose released into blood • Secretion stimulated by: • Low blood glucose •  activity of sympathetic NS (as w/exercise) •  a.a in blood if blood glucose is low (after high protein meal)

  13. Gluconeogenesis • Newly formed glucose • Non carbohydrate sources: • Lactic acid • Glycerol • Amino acids – about 60% of a.a. in body can be used for this • Stimulated by: • _______________(glucocorticoid) • _______________

  14. Gluconeogenesis fig 25.12

  15. Glucose tolerance • Test body’s ability to process glucose • Diagnostic for hypoglycemia, __________ __________, or malabsorption syndrome • Dependent upon ability of: • Pancreas to produce & release insulin • Cell response to insulin (membrane sensitivity) • Small intestine to absorb glucose • Liver to take up & store glucose

  16. Glucose tolerance (2) • ________ mg/100 mL blood =normal, fasting • “Load”  glucose  within 1 hour • Normal – followed by gradual decline • Abnormal – glucose levels remain elevated • Insulin response major factor • See lab manual, exercise 3 for more info

  17. Diabetes mellitus • Endocrine disorder, inability to produce (type 1) or use (type 2) insulin • 4th leading cause of death by disease in US • Type 1= insulin-dependent diabetes mellitus • ____________________ destroys pancreatic beta cells • Insulin injections required to prevent death • Type 2- non-insulin dependent • More common than type 1  >90% of cases • Often obese >35 yr, but, type 2 obese children & teens  • Target cells ____________ to insulin, downreg of receptors

  18. Lipoproteins are transporters • __________________- lipid & protein combination • Outer- proteins, phospholipids, & cholesterol • Proteins help solubilize lipids in body fluids • Inner core- triglycerides and other lipids • Categorized by _________ (lipids = low, proteins = high density) • Chylomicrons- s.i., many dietary lipids  adipose • VLDLs- very low density lipoproteins, form in hepatocytes, lipids adipocytes for storage or muscle • LDLs- carry ≈75% of total cholesterol in blood which goes to: • Cell membranes for repair, synthesis of steroid hormones, bile salts • When in excess deposit in smooth muscle of arteries  fatty plaque • HDLs- remove excess cholesterol from cells liver (elimination)

  19. Lipoprotein figure 25.13

  20. Pathways of lipid metabolism

  21. Metabolic regulation depend on: • Chemical environment in cell • ATP level • Oxygen • Nervous system • Endocrine system • Some functions of metabolism depend on- time since last meal

  22. Absorptive state figure 25.17 • Ingested ______________________ necessary for 2 main events of this state: • Oxidation of glucose for ATP production • Storage of excess food molecules occurring (for later use between meals) • Hepatocytes, adipocytes, skeletal muscle •  4 hours for complete absorption • _____________ dominates during this state

  23. Reactions (absorptive state) figure 25.17 • ≈50% glucose absorbed from meal  _________ • Most glu that enters liver (≈10%)  ___________ • Some f.a. & triglycerides syn in liver • Some stay in liver • Most  VLDLs to carry lipids to adipose • Adipocytes uptake glu (≈40%) _____________ • Most dietary lipids  adipose tissue • Chylomicrons, VLDLs, or synthesized • Many a.a. liver Krebs- ATP, or syn glu & fa • Some a.a.  hepatocytes synthesize proteins • a.a not taken up in hepatocytes  body cells • synthesis of proteins, hormones, or enzymes

  24. Absorptive state

  25. Regulation of metabolism- absorptive • GIP+  blood glu (& some aa)______________ • Insulin: (see table 25.3) •  enzymes of anabolism & syn to storage molecules •  enzymes of catabolism • Promotes glucose & a.a  ____________________ • Stim. phosphoyrlation of glu - hepatocytesG6P • Stim. G6P  glycogen in liver & muscle • Enhances _____________________(liver & adipose) • Stim. protein syn throughout body

  26. Postabsorptive state figure 25.18 • ________ of nutrients from GI tract ________ • Bodily energy needs being met by fuel already created • If no snacks, times  4 hours spent in postabsorptive state (late morning, late afternoon, most night) • __________________ involved in regulation • Glucose production & glucose conservation

  27. Postabsorptive – glucose production • ATP dominant fuel in ______ (fa can’t cross bbb) • RBC get ATP from glycolysis - lack mitochondria • Rxns that _____________________ in this state: • Breakdown of liver glycogen • Lipolysis • Gluconeogenesis using lactic acid • Gluconeogenesis using amino acids

  28. Postabsorptive– glucose conservation • Reactions to _______________ in this state: • Oxidation of fatty acids • Oxidation of lactic acids (in cardiac muscle) • Oxidation of amino acids (in hepatocytes) • Oxidation of ketone bodies • Can be used by heart, kidneys, & other tissue  ATP • breakdown of muscle glycogen • Glycogen  G6P (glycolysis)  ATP

  29. Postabsorptive state

  30. Regulation of metabolism – postabsorb • Hormones • ______________ hormones: • Glucagon-  gluconeogenesis & glycogenolysis • See table 25.4 for summary • Sympathetic NS • Glucose sensitive neurons activate release of NT norepinephrine • Adrenal medulla releases • Epinephrine – stimulates glycogen breakdown • Norepinephrine – both NE & E stimulate lipolysis

  31. Metabolism- fasting & starvation • ___________- w/out food several hours – few days • Glycogen stores depleted within hours • Protein catabolism > anabolism, aa gluconeo • _______________- weeks or months of food deprivation or inadequate intake • Triglyceride & proteins stores- last several weeks • Amt of adipose tissue determines survival time • During both: • Nervous tissue & RBC use glucose  ATP •  ketone bodies in hepatocytes  plasma  bbb •  glu needed for ATP syn,  need for gluconeo,  catabolism of muscle proteins

  32. Heat and energy • Heat- form of energy • Measured by temperature • Expressed in units- calories • calorie (cal) = amt of heat to  temp of 1g of water 1°C • cal is small  use kilocalories (kcal) or Calorie (Cal) • Core body temp = 37°C, shell = 1-6°C less • Too high  denatures body proteins • Too low  cause cardiac arrhythmias ( death)

  33. Heat production • ________________ • Hormones–thyroid, testosterone, insulin, hGH • _________________ – NE & E • Body temp -  body temp   biochem rxns • Ingestion of food – energy cost of digestion • ________ – child > elderly ( during growing) • Others: gender (males > females, exception- pregnancy ), climate, sleep, malnutrition

  34. Metabolic Rate • Overall rate at which metabolic rxns use energy • _________________- body quiet, resting & fasting • BMR- measure amt of oxygen used per kilocalorie of food metabolized • 1L ____________ to oxidize mix of carbs, proteins & fats  4.8 Cal of energy released • BMR ≈ 1200-1800 Cal/day in adults • Added calories needed: 500 small relatively inactive person  3000 for a person training for the Olympics • Accounts for ≈60% of energy expenditure

  35. Thyroid hormones & metabolism • TRH (hypothalamus)  TSH (pituitary) release thyroid hormones • ___________________ in skin & hypothalamus sense temp   TRH release • Thyroid hormones released in bloodstream • Slowly  _____________ by stimulating cell resp. • Cells use more O2  body temp  • 1°C rise in core temp  biochemical rxns by 10% • Part of negative feedback loop (fig 25.19)

  36. Vitamins–fat vs. water soluble, table 25.6 • Vitamins – organic nutrients- small amt to maintain growth & metab • Do not provide energy, function as coenzymes • Most must be ingested, cannot be synthesized • _______________ vitamins- absorbed w/dietary lipids in chylomicrons, need lipids to be absorbed adequate quantities • Can be stored in cells (esp. hepatocytes) • Vitamins A, D, E, K -- see table for functions • Water soluble vitamins- dissolved in bodily fluids • Excess quantities excreted in urine • Several B vitamins, vitamin C – see table • C, E and beta-carotene-________________________

  37. Vitamin Source Function

  38. Importance of minerals table 25.5 • Minerals – inorganic elements occur naturally in earth’s crust • 4% of total body mass, heavily conc in _____________ • Body generally uses ion form • Na – distribution of water, bicarbonate buffer, AP • K – generation & conduction of AP • Ca – form bones & teeth, clotting, nerve & muscle activity, endo & exocytosis, cell & chromosome motility, glycogen metab, rel NT & hormones • Fe – component of Hb & cytochromes in ETC • P – form bones & teeth, blood buffer system, nerve & muscle activity, energy transfer (ATP), part of DNA, RNA • I – req by thyroid to make hormones, reg metabolic rate

  39. Nutrition figure 25.20 • Nutrients- chemical substances in food body cells use (growth, maintenance, & repair) • Water, carbs, lipids, proteins, minerals, vitamins • Dietary Reference Intake (DRI)- or Recommended Daily Allowance (RDA) • http://fnic.nal.usda.gov/nal_display/index.php?info_center=4&tax_level=2&tax_subject=256&topic_id=1342&placement_default=0 • Proteins listed as macronutrients on website

  40. Amino acids • Building blocks for structural & functional cmpds in the body (enzymes, membrane carriers, hormones) • _______________amino acid or ________________amino acid – that which cannot be synthesized by the body and must be acquired through dietary intake • Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, theronine, tryptophan & valine • Nonessential amino acid – can be made by human body

  41. Protein types and sources • _____________ proteins – the 9 indispensible a.a. are found in animal sources – meat, fish, poultry, eggs, milk, cheese and yogurt • Incomplete proteins- sources that lack 1 of the 9 indispensible a.a., are found in plants, legumes, seeds, grains, nuts, & vegetables • Complementary protein combinations- those that give all the indispensible a.a. by combining incomplete with complete protein sources

  42. DRI establishment – see www.nap.edu • Are developed from recommended daily allowance & adequate intake • Increases from infancy thru childhood to adulthood- RDA = for males & females up to the age of 13 = 34 g/day • RDA levels off: • age 19-30 males = 56g/d • Age 14-18 females = 46g/d • Males have higher RDA than females • Pregnancy – double amt of 9-13 yr old girl (71g/d) • Lactation – same as pregnancy

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