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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 Heat and energy balance Nutrition Glucose Most glucose catabolized to make ATP Some used in anabolic rxns: To produce glycogen To produce more glucose from lipid and protein components Do not confuse these terms! Glucose Glycogen Glucagon Glycolysis Glycogenolysis Glycogenesis Gluconeogenesis Glycogenesis Glucose storage Occurs when glucose not immediately needed for ATP synthesis _____________- stimulates hepatocytes & skeletal muscle cells to carry out fig 25.11 From pancreatic beta cells ______________ - polysaccharide, polymer of glucose and only stored carb in our body 75% stored in skeletal muscle 25% in hepatocytes Glycogenolysis Glucose release Body activities require ATP glycogen stores in hepatocytes break down Glucose blood cells for catabolism fig 25.11 Glucose ATP Lactic acid (in muscle) glucose (in liver) Phosphorylase activated by ____________ (from pancreatic alpha cells) & ___________ (adrenal medulla) Reversal of steps in glycogenesis Glycogenesis & glycogenolysis Insulin Released in response to blood glucose pg 646-649 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 Fig 18.18 Figure 18.19 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) 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) _______________ Gluconeogenesis fig 25.12 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 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 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 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) Lipoprotein figure 25.13 Pathways of lipid metabolism Metabolic regulation depend on: Chemical environment in cell ATP level Oxygen Nervous system Endocrine system Some functions of metabolism depend ontime since last meal Absorptive state 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) figure 25.17 Hepatocytes, adipocytes, skeletal muscle 4 hours for complete absorption _____________ dominates during this state Reactions (absorptive state) figure 25.17 ≈50% glucose absorbed from meal _________ Most glu that enters liver (≈10%) ___________ Some f.a. & triglycerides syn in liver Adipocytes uptake glu (≈40%) _____________ Most dietary lipids adipose tissue Some stay in liver Most VLDLs to carry lipids to adipose 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 Absorptive state 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 - hepatocytesG6P Stim. G6P glycogen in liver & muscle Enhances _____________________(liver & adipose) Stim. protein syn throughout body 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 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 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 Postabsorptive state 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 Metabolism- fasting & starvation ___________- w/out food several hours – few days _______________- weeks or months of food deprivation or inadequate intake Glycogen stores depleted within hours Protein catabolism > anabolism, aa gluconeo 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 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) 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, exceptionpregnancy ), climate, sleep, malnutrition 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 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) Vitamins–fat vs. water soluble, table 25.6 Vitamins – organic nutrients- small amt to maintain growth & metab _______________ 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 Do not provide energy, function as coenzymes Most must be ingested, cannot be synthesized Excess quantities excreted in urine Several B vitamins, vitamin C – see table C, E and beta-carotene-________________________ Vitamin Source Function A, fat soluble Carotene (veg), liver, milk General health of epi cells, antiox. B complex, fat Whole grain, egg, pork, nuts, liver & yeast Citrus, tomatoes, green vegetables C, water D, fat K, fat metabolism, Ach synthesis, steroid hormones Protein syn, Ab, collagen form, antioxidant Fish-liver oil, egg Absorb Ca & P, yolk, fortified milk works w/PTH Intes bacteria, spinach, cauli, cabbage, liver Synthesis of several clotting factors by liver 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 Nutrition Nutrients- chemical substances in food body cells use (growth, maintenance, & repair) figure 25.20 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=25 6&topic_id=1342&placement_default=0 Proteins listed as macronutrients on website 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 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 DRI establishment – see www.nap.edu Are developed from recommended daily allowance & adequate intake Increases from infancy thru childhood to adulthoodRDA = 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