Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Energy—capacity to do work [Ch. 4, pp. 100-1](chemical, transport, mechanical)•Maintain ion gradients•Maintenance (e.g. turnover) & repair•Biosynthesis of new structure, other components•Movement (muscle contraction)•Reproduction•Lactation•ThermogenesisMetabolism: overall energy economy in a cell or organismCatabolism: breakdown of macromolecules (fuels) to obtain usable energyATP [big molecules  small molecules + ATP]Anabolism: use of energy (ATP) to produce new macromolecules [small molecules + ATP   big molecules]Energy Balance/Metabolism [Ch. 22]Energy balance: energy stored + energy intake – energy expenditure [Ch. 22, pp. 739-740]Energy expenditure = work + heatMETABOLISM & ENERGY BALANCE“La respiration est donc une combustion”--Anton Laurent Lavoisier 1780Oxidative energy metabolism is a form of “slow” combustionALL macro-nutrients feedinto the sameoverall pathwayaka: citric acid or Krebs cycleRotary engineof metabolismEnergy content of food—direct calorimetry1 Calorie = 1000 calories = 1 kcal = 4.184 kJ•Amount of heat needed to raise temperature of 1 liter of water by 1° C.•Yields “gross” energy of food•Includes combustion of indigestible components, e.g. “fiber”adiabatic bomb calorimeterIs this how energy content amounts in food labels are derived?•No—recall digestibility issues•W.O. Atwater, USDA (1900)—obtained gross energy values from various foods, applied corrections for digestibility, energy losses in urine; published series of tables of foodstuff energy contents•Several variations on Atwater’s general system, but his basic approach remains the basis for current food labeling policies, despite some significant problems [e.g. see Novotny JA et al, Am. J. Clin. Nutr. 6:296-301, 2012].Energy content of metabolic fuelsFat: 9 kcal (37.7 kJ/g)Protein: 4 kcal (16.7 kJ)/gCarbohydrate: 4 kcal (16.7 kJ)/gEnergy expenditure—indirect calorimetry [pp. 740-41]1 liter O2 consumed per 4.5 - 5.0 kcal released from metabolized foodMetabolic rate (kcal/day) = L O2 consumed/day * 4.8 kcal/L O2BMR—minimal rate for maintaining life, approximated by measurementof RMR (12 hrs postabsorptive state, resting)CO2 produced / O2 consumed = RQ --Yields general information on fuel composition--Under normal (well-fed) conditions, protein as a fuel is disregardedRQ varies with the fuel:--glucose:--glycerol palmitate: C16H32O2 + 23 O2 16 CO2 + 16 H2O RQ = 16 CO2 / 23 O2 = 0.7RQ = 6 CO2 / 6 O2 = 1.0Assumption: gas exchange measured at lungs = gas exchange during metabolisme.g. hyperventilation ↑’s CO2 elimination over and above O2 uptake  RQ > 1.0 Fuel usage can be estimated by the respiratory quotient (RQ) [p. 741]What influences metabolic rate? [pp. 741-42]•Age: as age ↑, MR ↓•Sex: MR♀ = 0.9 * MR♂•Lean muscle mass: as LMM ↑, MR ↑•Activity level: as physical activity ↑, MR ↑•Diet: eating meal ↑’s MR via thermic effect of food (aka “heat increment, HI”)—heat loss due to processes of uptake/assimilation/processing of nutrients--varies with nutrient—protein has highest HI•Hormones: thyroid hormones, epinephrine, norepi•Genetic factors: poorly characterizedMetabolism—overall biochemical processes mediating disposition of macronutrients (prot, CHO, fat) [pp. 743-45] oxidation for energy vs. biosynthesis vs. storage•Catabolism: large molecules  small molecules  ATP generation•Anabolism: small molecules + ATP  large molecules oxidation•Fed (absorptive) state: anabolic, fuels from food ATP storage oxidation•Fasted (postabsorptive) state: catabolic, body stores ATPUnder normal conditions, what determines whether metabolism goes in the direction of anabolism vs. catabolism?--the state of energy balancei.e. feeding vs. fastingWhat determines fed vs fasted state? [pp. 754-60]Blood Glucose Levels ratio of Insulin:GlucagonWhy is glucose so important?•Major metabolic fuel for all tissues, obligatory fuel for RBC’s, renal medulla, and under non-starvation conditions, the brain•Sole fuel for muscle contraction under “fight or flight” conditions•Provides anapleurotic precursors for citric acid (TCA) cycle•Provides carbon skeletons for synthesis of nonessential amino acids•Provides carbon precursors for TG components (glycerol & fatty acids)glucoseFate/uses for glucose:1) ATP production2) Glycogen (storage)3) Conversion to FA (storage)4) NEAA’s5) DNA, RNA1)2)3)4)4)4)3)5)Acetyl-CoAKey regulatory enzymes involved in a metabolic pathway are all activated or depressed in a coordinated manner—e.g. in fed state (↑insulin/glucagon):pyruvate dehydrogenase++++----Glucose6-phosphateglycogenGlycogensynthaseGlycogenphosphorylase+-glycogenesisFed State—fate of fuelsCarbohydrate (glucose)—higher insulin  + glucose utilization &energy storage; - FA, prot. breakdown - gluconeogenesis30%70%XXXXXFed State—fate of fuelsFat: dietary fat in CM bypasses liver, sparing FA for use by peripheral tissues; CMR carries cholesterol to liverWhen insulin/glucagon ↑: FA + glycerol   TG storage in adiposeFed State—fate of fuelsProtein: amino acids used for protein synthesis in liver and peripheral tissues •Excess not used for protein synthesis will be deaminated, carbon skeletons used for energy production or fat synthesispyruvate dehydrogenase++++----Glucose6-phosphateglycogenGlycogensynthaseGlycogenphosphorylase+-Gluconeogenesis-- ↑glucagon/insulin promotes reversal of glycolysisglycogenolysisucagonFasted State—fate of fuelsCarbohydrate (glucose) higher glucagon  - glucose utilization &energy storage; + FA, prot. breakdown + gluconeogenesisblood glucoseXXXXSee slides 29 & 30Fasted State—fate of fuelsFat: ↑ glucagon:insulin stimulates adipose HSL to de-esterify TG  glycerol + FFA, which circulate to liver for oxidation In adipose: In liver:glucoseRecall: glucose is needed to keep the TCA cycle goingKetosis– incomplete oxidation of fatty acids—due to combination of low levels of incoming glucose + high levels of incoming fatty acids