NUTR 4550 Exam 2 Study Guide
NUTR 4550 Exam 2 Study Guide NUTR 4550
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NUTR 4550 Exam 2 Study Guide Food Regulation Slide 2: Tissue-Fuels Used-Fuels Released Table ** Lactate released = Means incomplete oxidation of glucose (Pyruvate à lactate instead of pyruvate à acetyl CoA) • Brain: -‐ Fuels Used: o Glucose: Main source of fuel o Ketone bodies o Lactate (When the plasma concentration is elevated) -‐ Fuels Released: o Lactate -‐ Brain uses about 120 g of glucose per day -‐ Blood brain barrier does not allow most FA to be transported across so that’s why it will use ketone bodies instead (Glucose is #1 preference) -‐ Ketone bodies review: Not very high in concentration in a normal state unless an individual is following a ketogenic diet (High fat, low carbohydrates) + under starvation states (When food isn’t eaten for about a week or longer the glucose levels decrease à Depleted hepatic and muscle glycogen so there is a switching of fuels to ketone bodies) • Skeletal muscle: -‐ Fuels Used: o Glucose: Main source of fuel o Free FA o TAG o Branched-chain AA: Able to skip the liver when consumed and go straight to skeletal muscle o Lactate -‐ Fuels Released: o Lactate o Alanine o Glutamine -‐ Use of fuels depends on exercise: o High intensity at max: Glucose preference for energy and NOT fat -‐ Cori Cycle: o Ex: Sprinting (High intensity) à Produce lactate that goes back to the liver to produce glucose à Back out to cells for energy -‐ Glucose-Alanine cycle • Heart: -‐ Fuels Used: o Free FA o TAG o Ketone bodies o Glucose o Lactate -‐ Fuels Released: None o Holds onto fuels to be more efficient -‐ Cardiac muscle is constantly beating (~70 bpm) so there needs to be a constant fuel supply—Why FA or TAG is preferred -‐ Because the heart prefers FA, there is going to be a lot of mitochondria present in cardiac muscle • Liver: -‐ Fuels Used: o AA (Partial oxidation) o Free FA o Lactate o Glycerol o Glucose o Alcohol -‐ Fuels Released: o Glucose o Ketone bodies o Lactate (During absorptive phase) o TAG -‐ AA is the liver’s primary fuel source • Intestines: (Enterocyte) -‐ Fuels Used: o Glucose o Glutamine -‐ Fuels released: o Lactate o Alanine • Red Blood Cells: -‐ Fuels Used: o Glucose -‐ Fuels Released: o Lactate -‐ Do not contain mitochondria so there can’t be FA oxidation (Purely anaerobic respiration) • Kidney: -‐ Fuels Used: o Glucose o Free FA o Ketone bodies o Lactate o Glutamine -‐ Fuels Released: o Glucose (Renal gluconeogenesis important in prolonged starvation) • Adipose Tissue: -‐ Fuels Used: o Glucose o TAG -‐ Fuels Released: o Glycerol o Free FA o Lactate • Retina: Do not contain mitochondria so glucose is its main fuel source à Why see diabetics go blind when retina cells can’t take up glucose for energy Slide 3: AMP-activated protein kinase (AMPK) • AMPK is an intracellular regulator of fuel (Seen in most cells) • Low levels of fuel activate AMPK • Active AMPK = Phosphorylated • Inactive AMPK = De-phosphorylated • AMPKKs (Includes LKB, CaMKK, others) à Kinase protein that phosphorylates AMPK to make it active -‐ Calmodulin dependent kinase: Has the phosphorylation function and is regulated by allosteric regulators: ghrelin, IL-6, calcium, AMP, ATP, P- creatine (Phosphocreatine) • Allosteric regulators of AMPKKs that ultimately affect the activation or inhibition of AMPK: a) AMP: -‐ Increased AMP in the cell allosterically regulates AMPKK to phosphorylate AMPK (Active version) b) Ghrelin: -‐ Increased ghrelin allosterically regulates AMPKK to phosphorylate AMPK -‐ Hormone produced in the fundus of the stomach -‐ Stimulates food intake -‐ Some can be found in pancreas -‐ Acts on the hypothalamus and affects NPY and AgRP c) Calcium: Increased levels stimulate AMPKK à phosphorylate AMPK d) IL-6: Increased levels stimulate AMPKK à phosphorylate AMPK e) ATP and P-Creatine: Low levels stimulate AMPKK à phosphorylate AMPK • Active (Phosphorylated) AMPK regulates other processes in the body: a) ACC (Acetyl CoA Carboxylase) – Isoforms ACC1 and ACC2 -‐ Enzyme that initiates FAS by catalyzing acetyl CoA à Malonyl CoA -‐ AMPK inhibits ACC -‐ Energy is needed in the cell so acetyl CoA isn’t being used to make FA at this point -‐ Inhibition of ACC à decrease in malonyl CoA levels (FAS precursor) -‐ CPT1: o Carinitine transport protein (A transferase) located in the mitochondria that transports FA into the mitochondria from the cytoplasm for beta oxidation o Increased malonyl CoA levels inhibits CPT1 since malonyl CoA is a precursor for FAS à Don’t want to make and break down FA at the same time -‐ Overall: Low energy levels (High AMP) activates AMPK à Inhibits ACC à Decreases malonyl CoA levels à CPT1 inhibition goes away à FA transported into the mitochondria for beta oxidation b) NPY and AgRP -‐ Ghrelin allosterically regulates AMPKK to phosphorylate AMPK à Stimulates hypothalamic neurons à Stimulate NPY and AgRP to increase food intake and down regulate energy expenditure c) Rab-GAPs: Catabolic pathway -‐ Active AMPK inhibits rab-GAPs -‐ Rab-GAPs inhibit GLUT 4 translocation -‐ Inhibition of rab-GAPs allows the translocation of GLUT 4 to come to the plasma membrane and take up glucose d) 6PFK2: Catabolic pathway -‐ Active AMPK increases 6PFK2 in the heart -‐ Leads to increase in glycolysis e) Muscle LPL/CD36 translocation: Catabolic pathway -‐ Active AMPK stimulates LPL so that TAG à glycerol and FA in the muscle -‐ CD36: Transport protein that brings FA through the plasma membrane for they hydrolysis of FA in the cell -‐ Overall: Active AMPK up regulates LPL and CD36 to transport FA into the cell for break down to produce energy f) SREBP: Anabolic pathway -‐ Sterol responsive element binding protein -‐ 2 isoforms involved in lipid metabolism -‐ Signaling synthesis of cholesterol or FA -‐ Produced in the cytoplasm and goes to the nucleus where it functions in binding and expressing certain regions of DNA that produces mRNA and protein nuclear transcription factor g) HMG-CoA Reductase: Anabolic pathway -‐ Enzyme in cholesterol synthesis -‐ Active AMPK inhibits HMG-CoA reductase which down regulates sterol/isoprenoid synthesis (Want to make energy not build things) h) Glycogen synthase (GS): Anabolic pathway -‐ Active AMPK inhibits glycogen synthase i) mTOR: Anabolic pathway -‐ Protein involved with protein synthesis -‐ Active AMPK inhibits mTOR -‐ Branched chain AA are stimulators of mTOR Slide 4: mTOR (Know general process) • mTOR protein is active when cell wants to synthesize especially protein • Insulin (Growth factor) • IGF1 (Growth factors): -‐ GH binds to GH receptors on the liver to produce IGF1 -‐ IGF1 increases at not or in response to exercise • Insulin and IGF1 bind to tyrosine kinase receptor à Intracellular processes to activate mTOR • BCAA help regulate mTOR—Especially leucine that activates mTOR • Whey protein: Consume after workout -‐ High in leucine -‐ Stimulates mTOR to synthesize protein (Building muscle) • Low intercellular ATP and high AMP: -‐ AMPK is active which causes mTOR to be down regulated -‐ Don’t want to up regulate protein synthesis with mTOR when the cell needs energy • Hypoxia: -‐ Regulator of mTOR -‐ Low concentrations of oxygen inhibit mTOR • When mTOR is activated due to the binding of insulin/IGF2 à Cascade of events + inhibition of autophagy -‐ Autophagy is a process involved with cell housekeeping -‐ Cell cleans up damage to organelles, fixes misfolded proteins, etc. -‐ Active mTOR inhibits autophagy (Don’t want to degrade proteins) Slide 5: Pancreas • Endocrine portion: Secretes insulin and glucagon (Focus) • Exocrine: Secretes digestive enzymes à Duodenum • Absorption of nutrients from the small intestine à liver • Pancreas is located right by the liver to detect what was just consumed in order to release corresponding signals (Anatomy of the organs is very important) • When a mixed meal is consumed, glucose is taken up by the pancreas by GLUT 2 and is trapped by the cell via phosphorylation à glucose-6-phosphate via glucokinase = Initiation of pathway stimulates the release of insulin from the pancreas • Amylin: Released in conjunction with insulin à Job is to signal the brain to regulate nutrient levels Slide 6: Glucose Homeostasis • Normal fasting range for blood glucose levels: 70-100 mg/dL • Consumption of a mixed meal with carbohydrate: -‐ Insulin levels increase -‐ Glucagaon levels decrease -‐ Insulin binds to receptors on the liver -‐ Glucose uptake by liver -‐ Synthesis of glycogen -‐ Increase in FAS -‐ Down regulate gluconeogenesis to keep blood glucose range 70-100 mg/dL • Skeletal muscle: Fed State -‐ Store glucose as glycogen -‐ Take up excess glucose and make FA in adipose tissue and when glycogen stores are filled • Low levels of glucose: Fasted state -‐ Decrease insulin levels -‐ Increase glucagon levels -‐ Acts on muscle and liver to increase gluconeogenesis and glycogenolysis -‐ Muscle: Decrease glucose uptake and likely using glucose from glycogen + FA + ketone bodies Slide 7 • X axis: Gives the time after a meal • Fed and post absorptive state: Refers to right after a meal is consumed—30 minutes – 3 hours then get into fasted state • When glucose levels decrease, insulin levels decrease à Due to the uptake of glucose by GLUT 4 in adipose tissue and muscle (Want to keep range around 70- 100 mg/dL) • When there are elevated levels of glucose and insulin, see a decrease in glucagon Slide 8 • Insulin binds to tyrosine kinase receptor à Intracellular signaling of a cascade of events in the phosphorylation of proteins • Binding of insulin: -‐ Up regulation of GLUT 4 translocation to the plasma membrane -‐ Excess glucose à FAS -‐ Glucose à glycogen synthesis (Glycogen synthase up regulated) Slide 9 • 7 transmembrane G protein couple receptor: -‐ Receptor that glucagon and epinephrine binds to -‐ Transverses the plasma membrane 7 times -‐ Uses GDP protein complex in the cascade of events • Alpha subunit of GDP activates adenylate cyclase (An integrated protein in the plasma membrane) that increases cAMP levels à Increases protein kinase A that affects different processes downstream • Protein kinase A effects: -‐ Glycogenolysis increase via protein kinase A phosphorylating glycogen phosphorylase (Active form) o Release of glycogen from liver à Heaptic glycogen is able to leave the liver o Skeletal muscle glycogen cannot release glycogen but releases glucose -‐ Stimulates gluconeogenesis o CREB mediated transcription factor: Transcribes certain sections of DNA that are specific to certain proteins o Glucagon upregulates CREB through protein kinase A o CREB increases levels of gluconeogenic enzymes (Pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase) -‐ Stimulates lipolysis o Up regulation of HSL that increases the release of FA and glycerol from adipose tissue o FA go to the liver to be converted to ketone bodies in the starved state o FA can also be packed into VLDL and be secreted to go towards beta oxidation in cells for energy Slide 10: Summary Slide • Insulin à Increases mTOR, glycogen synthesis, protein synthesis, TAG storage, gene transcription of ACC to produce malonyl CoA, inhibition of autophagy • Low glucose levels: cAMP increases to turn on PKA + break down glycogen, increases gluconeogenesis, VLDL synthesis, and ketone synthesis Slide 11: Figure 19.9 • In the morning: When one eats breakfast, can see an increase in glucose, lactate, and ketone bodies • Lactate: Incomplete oxidation of glucose; Cells aren’t 100% efficient with converting glucose to pyruvate to acetyl CoA • Ketone bodies: Concentrations are relatively constant à Assume person is healthy and not on a ketogenic diet • Glycerol: Concentrations are relatively constant • Amino Acids: Concentrations increase a slightly because a mixed meal was consumed • TAG: Concentrations increase • Overall: The body is exceptional in regulating these various components à Most levels decrease by about 2-3 hours after consuming the meal = Why we eat in phases Slide 12: Figure 19.10 • Figure shows how 90 g of glucose is portioned between different tissues • 15-20 g of glucose will go towards the brain -‐ The brain oxidizes 120 g of glucose per day • Liver takes up about 20 go of glucose for glycogen storage • The majority of glucose goes to skeletal muscle because it is a large tissue—Will receive 20-45 g -‐ 20 g goes towards oxidation -‐ 45 g goes towards glycogen • Small amount of 2 g of glucose goes to adipose tissue • Ex: On ketogenic diet for 8 weeks: -‐ Low carbohydrate, high fat -‐ Brain would use ketone bodies -‐ Liver: Makes the ketone bodies and is likely depleted of all glycogen stores -‐ Maybe using a little bit of glucose -‐ If the diet includes a little protein, the dietary protein will be used for energy -‐ Skeletal muscle is likely using proteins and fat as energy source Slide 13: Figure 19.11 • Figure shows changes in glucose, insulin, and glucagon over days of starvation • At 40 days of starvation: The blood glucose level will not change • Most glucose is produced through gluconeogenesis • Pyruvate precursors: Alanine + carbons à Used to make glucose Slide 14: Figure 19.12 • As an individual moves into 7, 14, 21 days of fasting, can see an increased concentration of acetoacetate and beta hydroxybutyruate (Ketone bodies) Regulation of Fuel Utilization in Response to Exercise Slide 4: Muscle Fiber Types • Type 1 Red Fibers Slow Oxidative Fatigue Resistant: -‐ “Red” because of how the muscle fiber stains when looking at histology -‐ Has high levels of myoglobin (Transports oxygen in muscle cells) -‐ Oxidative: Has high concentration of mitochondria -‐ Contract very slowly -‐ Found in muscles that can be used for excessive periods of time -‐ Fatigue resistant: Takes a long time for these muscles to fatigue because of the high oxidative capacity -‐ When exercising and using weights, slow twitch fibers are going to be recruited first and then as one gets tired, fast twitch fibers are recruited -‐ ATP generated through aerobic respiration: Glucose à pyruvate à acetyl CoA à TCA cycle à intermediates à ETC à oxygen (Final electron acceptor) -‐ Capillary density is high -‐ Low glycolytic capacity: Anaerobic glycolysis (Pyruvate à lactate) is found more so in fast twitch fibers but still want glycolysis around for the slow twitch fibers -‐ Creatine phosphate -‐ Glycogen intermediate low: Slow twitch fibers are more oxidative so mainly using FA as fuel source (High TAG content) à Glycogen content is going to much lower as a result -‐ Not a lot of force is produced by these slow twitch fibers à As a result, a 1 repetition max will be completed where one works up to one rep at the heaviest case possible (Fast twitch fibers create a lot of force) -‐ Activity use: Mainly aerobic à Running, cycling, long-distance activities, standing walking -‐ Calf muscles • Type 2A Red Fibers Fast Oxidative Fatigue Resistant: -‐ In between slow and fast twitch muscle fibers -‐ Fast, oxidative, and fatigue-resistant -‐ Recruitment order: Intermediate -‐ Seen with exercises from long-distance running to sprinting -‐ Intermediate mitochondrial density -‐ Intermediate oxidative capacity -‐ Have many glycolytic enzymes for oxidative phosphorylation and anaerobic glycolysis -‐ Creatine and glycogen stores are high in these muscle fibers -‐ Fast contraction velocity • Type 2X White Fast Glycolytic Fatigable: -‐ Very fast contraction velocity à Respond quickly -‐ Fatigue rapidly -‐ Stain white because have low levels of myoglobin -‐ Recruitment order: Late à As one gets tired, these muscles are recruited later -‐ Used for sprinting and short-term exercises -‐ Myoglobin content is low: Don’t have a lot of mitochondria so don’t need to be carrying as much oxygen to here -‐ More anaerobic for ATP production: Anaerobic glycolysis—pyruvate à lactate -‐ Low capillary density -‐ High glycolytic capacity -‐ High creatine content -‐ High glycogen content -‐ Won’t use a lot of FA for fuel -‐ Quad muscles • Genetic factor plays a role in determining what type of muscle fiber you have • 99.9% of mitochondria is derived from the mother • Able to change some of the fiber types with exercise à HIIT and sprint training can increase the level of 2A intermediate twitch fibers so there is a blend of oxidative and fast twitch fibers Slide 5: Figure 20.3 • Looking at energy expenditure • At rest, the energy expenditure in a marathon is much lower than in a sprint • Whole body and skeletal energy expenditure is about the same à Can conclude that skeletal muscle accounts for a large percent of the energy expenditure during exercise • HIIT: Energy expenditure is increased during and after exercise • Lean muscle plays a huge factor on whole body energy expenditure • Resistance training recommended for those who wish to lose weight and increase lean muscle mass Slide 6: Figure 20.4 • Looking at the duration of exercise at 70% VO2max • 70% VO2max: Volume of oxygen that you can consume at maximal capacity -‐ Usually written in mL/kg/min -‐ Average for females: 30-40 -‐ Average for males: 40-50 • Figure is for males that had their VO2max measured for a baseline and then they ran then took blood samples -‐ Blood samples showed plasma fuel concentration (What fuels were being used during exercise) • 0-120 (X axis): -‐ Fuel sources started to change -‐ Glucose presence started to decrease (Because it’s likely that the glucose was being used for energy) -‐ Lactate changes by increasing at the start of exercise (Anaerobic respiration at this point) but then levels off around 120 -‐ FA presence increased (Occurs especially as get into longer exercise times) • FA change the most because as glucose levels go down and get more in a steady state, FA can then be used and are released into the bloodstream from adipose tissue so FA concentrations increase in the blood • Glycerol levels increase: Mirrors the hydrolysis of FA from TAG • Increase the intensity of exercise: Ex: 90% VO2max -‐ Won’t be using slow oxidative muscle—The shorter, 2X fibers are mainly used (Can’t withstand fatigue like slow oxidative) -‐ Likely using the higher force -‐ More reliant on glucose for HIIT and FA use decreases -‐ Glucose coming from glycogen stores -‐ Lactate levels increase Slide 7: Figure 20.5 • Figure gives data based on healthy, young individuals • As insulin decreases, glucagon increases à Catabolic in stimulating the release of glucose from the liver from hepatic glycogen (Levels out once reach recovery state) • Exercise itself is catabolic • Cortisol: Does not change that much because this is a steady state form of exercise shown -‐ When exercise as one’s max and taking part in resistance training/sprints à Likely that there is an increase in cortisol • Norepinephrine and epinephrine increase mirror glucagon -‐ Mobilizing energy stores -‐ Increasing glycolysis -‐ Increase FA concentrations -‐ Using glycogen and glucose • Olympic athlete: Can have from 70-80 VO2max (Higher than average individual) • Overall: As one is exercising, ATP levels decrease and AMP levels increase à An intercellular signal will act when there is AMP present to activate AMPK by phosphorylating it via AMPKKs à downstream effects to help the cell obtain energy Slide 8 • Higher intensity exercise relies more on muscle glycogen • Low intensity exercise (40-35% VO2max or less) uses mostly FA -‐ White area under the curve = plasma free FA • Moderate intensity exercise (50-60% VO2max): See an increase in muscle glycogen • Max VO2max (80% +): Most fuel is coming from glycogen levels à anaerobic glycolysis • Liver: 80-100 g of glycogen stored • Muscle: 300-500 g of glycogen stored à Some people can store up to 900 g depending on how much they have • More fat can be stored than glycogen because water is stored with glycogen and this takes up a lot of space • Fat is smaller and doesn’t take up as much space • If able to store as much glycogen as fat, individuals would be 4x the size they are now Energetics PPT 1 (2/12/2016) Slide 1: Energetics • Creatine phosphate is used in skeletal muscle when undergoing high-intensity exercise • Creatine can be found in food and supplements • Creatine is the initial main supply of energy from creatine stores (Animal protein stores) à ~ 30 seconds • Creatine-P + ADP à ATP + Creatine • Then: ATP à ADP + Pi • Creatine allows one to work more in an anaerobic environment for a longer period of time • Use glycogen next, depending on the intensity of the exercise and then lastly stored fat (TAG) from skeletal muscle or adipose tissue • At the same time, lactate is being made (Glucose à pyruvate à lactate) • Lactate can go to the heart and liver • Liver: Lactate à Cori cycle à produce glucose à Used by skeletal muscle again • Lactate isn’t bad but is associated with lower exercise performance • Insulin binds to tyrosine receptor to have GLUT 4 take up glucose in skeletal muscle • While exercising, GLUT 4 is stimulated to go to the plasma membrane without the presence of insulin • Lower intensity exercises mainly use FA Slide 2: Figure 21.2 • Energetics: Energy expenditure • Energy: The capacity to do work; Our bodies have the capacity to turn food into energy • Energy is the substrate of work • 4 types of energy: Electrical, chemical, osmotic, and mechanical • If there is carbohydrate, lipids, and AA present, ATP is being created via substrate level phosphorylation (Glycolysis and TCA cycle) and oxidative phosphorylation (ETC) • Energy is measured in Joules, kcals, and watts • Calorimetry is used to measure kcals • Calorie: Energy required to raise 1 g of water 1 degree C • 1000 kcal = 1 calorie • When something is oxidize, carbon dioxide and water are always the by products • Oxidation of glucose: Glucose + 6 O à2 6 CO + 2 H O +2heat (3.8 kcal/g) • In the figure, the thicker the line, the more energy required for the corresponding process • Heat is always given off so not efficient • See uncoupling in infants à Infants have brown adipose tissue that generates heat since they don’t have the development to stay warm and generate their own heat • Membrane transports 20-30% ATP sodium potassium ATPase (A lot of energy we create goes just towards maintain the sodium-potassium pump) • T3 and T4 are regulators Slide 3: Figure 21.3 • Figure of a mitochondria with the macronutrients at the top (Protein, glucose, TAG) • ATP synthase is used to make ATP—Oxidative phosphorylation • During oxidative phosphorylation, carbond dioxide and O 3 • Beta oxidation: Palmitic acid + 23 O à 26 CO + 16 H2O + heat2(9.3 kcal/g) -‐ Palmitic acid requires more oxygen than carbon dioxide so get more energy per gram • Direct measuring of calories measures the heat produced by an individual • Indirect measuring of calories measures how much carbon dioxide is produced and oxygen is consumed • REE (Resting Energy Expenditure): Amount of energy needed to maintain basic metabolic function—Measured in kcal/day • RQ (Respiratory Quotient): VCO /VO 2 2 -‐ At a volume of 1, carbohydrates are mainly used at rest (6 CO / 6 O 2 1) 2 -‐ Can tell which sources of fuel the body is using with RQ -‐ Ratio of CO2 produced to O2 consumed while food is being metabolized: RQ = CO 2 eliminate2 consumed -‐ RQ of palmitic acid: 0.7 -‐ Oxidation of macronutrients: o Fats: Lower o Proteins: Middle o Carbohydrates: Higher Slide 4: Electron Transport Chain (Figure 21.4) • Production of ATP comes after the ETC with ATP synthase • ETC functions to move hydrogen ions from the matrix of the mitochondria to the inner membrane space + • Complex I: Pumps 4 H into the inner membrane space • Complex III: Pumps 2 H into the inner membrane space + • Complex IV: Pumps 4 H into the inner membrane space • Start with NADH that interacts with complex I so that the released electrons move down complexes I-IV à A total of 10 protons is moved from the matrix to the inner membrane • Start with FADH tha2 donates electrons at complex II and moves protons at complexes III and IV à A total of 6 protons is moved from the matrix to the inner membrane space • It is required for 4 protons to make 1 ATP (Through phosphorylation of ADP in ATP synthase) • NADH: Generates a theoretical maximum of 2.5 ATP • FADH : G2nerates a theoretical maximum of 1.5 ATP Slide 5: Figure 21.5 • Figure demonstrates how the body captures and uses energy • Total energy intake: -‐ Comes from food that is being consumed and all the energy contained within that food (Combustible energy value of foodstuff) -‐ AKA measure heat generated from the combustion of food if it was set on fire to determine the total energy of the food • Digestible energy intake: -‐ What is absorbed from the GI tract -‐ Arrow between total energy intake and digestible intake: Offshoot indicating that some of the total energy intake is lost as feces (5-10%) • Metabolizable energy: -‐ What is available for use by cells of the body or caloric value of foods -‐ Arrow between digestible energy and metabolizable energy: Offshoot indicating that some digestible or absorbed energy is lost in urine (2-3%) • Caloric values of food: -‐ Carbohydrate: 4 kcal/g -‐ Protein: 4 kcal/g -‐ Lipids: 9 kcal/g -‐ Alcohol: 7 kcal/g • Comparison of metabolizable energy to the combustible energy (total energy intake) of food: -‐ The difference is off by a different percentage for each food -‐ For carbohydrates and lipids: Metabolizable energy is close to the combustible energy (original total energy intake) -‐ For protein: Metabolizable energy is off by about 25% compared to the combustible energy (original total energy intake) • Moving down the diagram: Metabolizable energy (100%) -‐ Have heat loss when energy is being used due to biochemical inefficiency of converting energy into ATP -‐ 60% of the metabolizable energy is lost as heat -‐ This is not really considered a loss since the heat is necessary to maintain body temperature à Otherwise, enzymes would not function as well above or below 98.6 degrees F • Energy available to couple work (40%) -‐ Energy converted to high-energy bonds of ATP -‐ Have heat loss due to the biochemical inefficiency of coupling ATP to work -‐ Where ATP is being utilized and the high energy phosphate bonds are being broken to perform work -‐ 24% of the energy available to couple to work is lost as heat • Energy actually used to accomplish work (16%) -‐ Includes mechanical work such as respiration and circulation, transport work, synthetic work, and muscle contraction -‐ 12% of the energy actually used to accomplish work goes towards the dissipation of heat in the body as a consequence of internal work and muscle contraction to generate force for external work • External work done on the environment (2%) -‐ Energy lost as heat (Ex: due to friction) or temporarily stored in the environment as non-heat energy as a consequence of external work -‐ (Goes to 0%) • Overall, a relatively small amount of energy from food goes towards producing or using ATP • The inefficiencies and heat production are important • When the body starts to get too warm, it dissipates heat so that the body temperature doesn’t rise too high Slide 6: Electron Transport Chain, ATP Synthase, and UCP • In the electron transport chain, protons are moved from the matrix to the inner membrane space • ATP synthase makes ATP by shuttling protons back through the enzyme complex to produce energy for the phosphorylation of ADP à ATP • UCP: Uncoupling protein -‐ Where in the mitochondrial membrane protons are leaking into the matrix of the mitochondria from the inner membrane space -‐ Seen as an inefficiency but this is important in maintaining body temperature since there is some heat generation when the protons leak into the matrix -‐ Especially important for babies: o Necessary to generate heat without movement – Uncoupling proteins allow babies to keep their proper body temperature since they aren’t able to maintain their own temperature yet o Evolutionary link: People that lived in cold climates long ago didn’t have the proper outwear à Uncoupling proteins were up regulated as a result to allow for more leakage of protons Energetics PPT 2 (2/15/2016) Slide 2: Figure 21.7 • Figure shows the generation of fat cells from adipocytes • On the right: There is a precursor for one white adipocyte and pre-adipocyte differentiation -‐ After differentiation, the adipocyte is able to store fat and energy • On the left: There is a precursor for brown adipocyte and skeletal myocyte -‐ Left arrow: Myogenic determination factors à Skeletal myocyte -‐ Right arrow: Adipocyte determination factors à Brown adipocyte • White Adipocyte: -‐ One large lipid droplet • Brown Adipocyte: -‐ Contains more mitochondria -‐ Smaller lipid droplets -‐ Generate heat -‐ Able to store lipid for energy but more so thought of as a heat generating cell -‐ Mitochondria have the uncoupling proteins that allow the leakage of protons from the inner membrane space à Generation of some heat • Arrow from white to brown adipocyte-like cell: -‐ White adipocyte can go through browning through some environmental cues (Ex: Cold weather) -‐ Browning of fat tissue develops more smaller lipid droplets that generate more mitochondria -‐ Contributes to helping maintain body temperature • Infants: -‐ Contain more brown adipose tissue -‐ As humans age and get bigger, we are able to more easily maintain body heat -‐ Therefore, less energy needs to be put into maintaining body temperature • Other consequences of brown adipocytes or brown adipocyte-like cells: -‐ Have uncoupled the transportation of protons from the matrix into the inner membrane space for ATP production -‐ Now, protons are pumped into the mitochondria to make heat (Not getting anything out of it traditionally like ATP) -‐ Related to a possible link to weight maintenance: Increase uncoupling proteins and therefore heat production à Use more energy as a result and not produce more ATP Slide 3: Figure 21.8—Alternative Process in Generating Heat for Body Temperature Maintenance • Fructose-6-phosphate à Fructose-1,6-bisphosphate via PFK -‐ Reaction consumes 1 ATP to generate ADP • Fructose-1,6-bisphosphate à Fructose-6-phosphate via fructose bisphosphatase -‐ Remove phosphate group and generate inorganic phosphate instead of going back to ATP -‐ Consume water too • Bottom right: Net effect—ATP + H O à ADP + P + Heat 2 i -‐ Alternative process that can generate some heat -‐ Relates to maintain core body temperature Slide 4: Figure 21.9 • Figure shows the breakdown of how energy expenditure is distributed throughout the course of one day (BEE, TEF, and EEPA) • BEE (Basal Energy Expenditure): -‐ Minimum amount of energy required to keep an individual alive- ~1,500 kcal/day -‐ Nervous system, heart beating, transport systems, glycolysis, beta-oxidation, TCA cycle, etc. -‐ Measure BEE in a sleeping state • REE (Resting Energy Expenditure): -‐ When a person is generally awake but resting -‐ Slightly higher than BEE • TEF (Thermic Effect of Food): -‐ ~200 kcal/day -‐ Digestion, absorption, mastication (Chewing with some muscular contraction), GI tract movement -‐ Digestion: Includes production of enzymes and hormones that facilitate digestion, regulation, and metabolism -‐ Absorption: Includes most nutrient transporters by sodium-potassium pumps that facilitate transport -‐ Assimilation: Utilization of nutrients and cells by tissues o Ex: Lipids: Uptake into adipose tissue or muscle + stored as TAG o Ex: Glucose à glycogen -‐ All nutrients contribute towards TEF, but the biggest contributor is protein -‐ Protein TEF: o In terms of energy, protein = 4 kcal/g (This is the metabolizable energy) o Oxidizable energy = 5.4 kcal/g o Some energy is inherent to AA/proteins with the amine group o When harvesting energy from AA, protein, body can’t use the energy in the bond of the amine group o Breaking down AA à deamination so the amine group is lost as NH 3 o Therefore, AA metabolism isn’t as efficient as lipid and carbohydrate • EEPA (Energy Expenditure Physical Activity): -‐ ~750 kcal/day comes from any form of physical activity (Walking, talking, etc.) -‐ Most likely less than 750 kcal/day though -‐ Moderate- highly active people will burn 750 kcal/day • GI Tract: Major fuel source is AA Slide 5: Figure T21.1 • Complete Oxidation of Food Component by Burning: -‐ If the food is set on fire, able to measure the amount of energy gained from that nutrient -‐ Carbohydrate: 4.1 kcal/g -‐ Fat: 9.3 kcal/g -‐ Protein 5.4 kcal/g • Complete Oxidation of Absorbed or Stored Fuel in Body: -‐ Carbohydrate: 4.1 kcal/g -‐ Fat: 9.3 kcal/g -‐ Protein: 4.2 kcal/g à *Shows how there is some inefficiency with using protein as an energy source in comparison to carbohydrate and fat • Physiological Fuel Value of Consumed Foodstuff (Some energy is lost as heat, through feces, urine, etc. so this gives how much energy the body can actually use) -‐ Carbohydrate: 4 kcal/g -‐ Protein: 4 kcal/g -‐ Fat: 9 kcal/g • RQ (VCO /VO ) of fat, protein, and carbohydrate: a) Fat: RQ of 0.71 2 b) Protein: RQ of 0.8 c) Carbohydrate: RQ of 1 *Think of these values generally as non-protein RQ à In most cases, protein isn’t being used as an energy source; Energy macronutrients are generally held to carbohydrate and lipids • When will see protein used as an energy source: -‐ Prolonged starvation -‐ Individual on a diet to lose weight -‐ Individual on a specific diet that is low in carbohydrate • Can measure the nitrogen in urea to determine how much protein is catabolized à Assume no protein oxidation though most of the time Slide 6: Figure 21.11 • Figure demonstrates the breakdown of energy as one ages • Distribution of RMR (Resting metabolic rate) on the y-axis and age on the x-axis • Brain: Changes seen -‐ RMR value decreases with age -‐ Infants require a lot of energy use in the brain initially (Nervous development) • Muscle: Changes seen -‐ RMR value decreases with age -‐ Significant muscle growth occurs around puberty • Liver: Changes seen -‐ RMR value increases with age -‐ Increase due to detoxification à Toxins in the body start picking up especially around the age of 21 when drink more so energy needs to be devoted to detoxification -‐ Also due to regulating the whole body energy status—Storing and using glycogen, synthesizing and breaking down FA, ketone body production -‐ Efficiency with maintain body heat • Heart, kidney, and adipose tissue remain relatively constant -‐ As long as the heart betas, the kidneys are always filtering blood (Function does not change) -‐ Adipose tissue à Born with it, live with it, and die with it; Doesn’t require a lot of energy in storing fat • Everything else: Slightly decreases with age Slide 7: Figure 21.12- Whole Body RMR vs. Liver, Kidney, Brain, and Heart RMR across a life-span • Figure shows how RMR changes with time • As an infant, a lot of energy is expended per kg of body weight à Due to dissipating body heat especially • As one ages, the energy expended decreases per kg of body weight • Power of ¾: 3/4 -‐ Across most mammals, you are able to take bodyweight to get an estimation of body expenditure -‐ As the bodyweight value gets larger, a smaller number results for the RMR à AKA a small number to ¾ = more kcal/kg body weight vs. a large number to ¾ = less kcal/kg body weight -‐ As our bodies get bigger with age, they get more efficient • Liver, kidney, brain, and heart: -‐ All combined remain relatively constant across the life span -‐ Liver RMR goes up -‐ Brain RMR goes down -‐ Heart goes up -‐ Kidney stays about the same -‐ Therefore, the sum of all of these = RMR remains about the same so the same amount of energy (~350 kcal/day) is used by the vital organs to function with age -‐ Everything else drops off significantly Energetics PPT 3 (2/17/2016) Slide 2: Figure 22.1 • Energy balance: Energy in = energy out • Positive energy balance: Energy in > energy out à Increase in energy stores to maintain energy balance • Negative energy balance: Energy in < energy out à Decrease in energy stores to maintain energy balance Slide 3: Figure 22.1- Estimate of body stores • TAG: -‐ Stored in adipose tissue -‐ 140,000 kcal à kcal from this is regularly used for energy production • Protein: -‐ Stored in muscle -‐ 25,000 kcal is associated with muscle -‐ Generally not used for energy production unless one is on a diet to lose wait or in the starvation state • Glycogen: -‐ Stored in liver and muscle -‐ 1,400 kcal is associated with this tissue -‐ Used all the time especially in the liver to maintain blood glucose concentration • Glucose or lipid: -‐ Stored in body fluids -‐ Lipid in the blood is more dependent on excess carbohydrate and fat consumption Slide 4: Figure 22.2 • Figure shows fat stores on the bottom, protein stores in the middle, and carbohydrate stores on top • Energy in is on the left and energy out is on the right of the energy stores • 71% of daily oxidation comes from carbohydrate storage à Because carbohydrate is the preferred source of energy in the body • <1% of daily oxidation and nutrient balance comes from fat • Carbohydrate oxidation is for the brain or RBC especially, and lipid oxidation is for different pathways in generating ATP Slide 5: Figure 22.2 Slide 6: Figure 22.3- Basic Overview of Energy Balance • Left side: System energy balance • Right side: Controller of central nervous system • Figure shows what is going on to maintain body’s energy status and NOT what is regulating body weight/composition • Energy balance is to make sure that an individual has enough energy to carry them throughout the day • Energy balance means that all the inputs and outputs should come out equally • Various peptides, hormones, and vagal afferents work to control inputs to control changes of output in relation to changes in food intake and energy expenditure Slide 7: Figure 22.5 • Hormones and regulating peptides function to control energy status within the body • Consumed meal: -‐ Glucose, AA, and FA nutrients come into the body and circulate -‐ Sensing of these nutrients -‐ Consuming a meal leads the brain to signal inhibition of anymore food intake (Slow down) -‐ Overall: The GI tract and circulation of the nutrients in the blood signals the body to slow down consumption • Adipose: -‐ Contains leptin hormone that signals inhibition of food intake -‐ Leptin production is directly produced to the fat content in the body à The more fat, the more leptin produced to signal a reduction in food intake -‐ Leptin is not dependent on the transport of FA or the storage of TAG -‐ Long-term energy sensor -‐ Obese Individuals: May have inborn error in leptin production or receptor, etc. • Pancreas: -‐ Insulin, amylin, and PP (Peptide P) -‐ Insulin focus à Glucose presence increases insulin production à downstream events with one being inhibition of food intake • GI Tract (Small Intestine): -‐ CCK, PYY (Peptide YY), GLP-1, OXM -‐ Hormones produced within the GI tract that signals the body to reduce food intake • Stomach: -‐ Ghrelin -‐ Produced in the fundus of the stomach -‐ Only hormone that signals an increase in food intake • Emphasis is placed on inhibition of food intake rather than activation: -‐ From an evolutionary standpoint, one is always going to want to eat -‐ Too much of anything can be damaging to the body -‐ Reason may not have even been discovered Slide 8: Figure 22.3 • Table describes hormones that have an effect on eating + where they are produced • Glucagon: Decreases with food consumption • Insulin: Signals decrease in food intake • CCK from the GI tract signal decrease in food intake • Ghrelin signals increase in food intake Slide 9: Figure 22.6 • Top Portion: Figure A—Orexigenic pathway -‐ Orexigenic pathway: Stimulates food intake -‐ Aanorexigenic pathway: Inhibition of food intake -‐ More adipose tissue (Larger adipocytes shown in A than in B)à More stored energy à Increase in leptin production -‐ Pancreas: o More adipose tissue à More food consumed à Insulin up regulated -‐ NPY and AgRP proteins produced in neurons o Ultimately signal changes in appetite o Increased insulin and leptin down regulate NPY and AgRP o Less NPY à Less binding to orexigenic neurons o Because AgRP is not present as a result of inhibition by increased leptin and insulin, MSH is able to bind to the receptor to signal the anorexigenic pathway -‐ Overall: Increased leptin/insulin à Inhibition of producing NPY and AgRP à Less signaling of the orexigenic pathway and signaling by MSH for the anorexegenic pathway to reduce food intake and increase energy expenditure • Bottom Portion: Figure B—Anorexigenic pathway -‐ Less adipose tissue (Smaller adipocytes shown in B than in A) à Less stored energy à Decrease in leptin production -‐ Decrease in insulin production from the pancreas -‐ NPY and AgRP proteins o Increase in NPY à Binding of the receptor à Stimulate orexigenic neurons à Increased food intake and decrease energy expenditure o AgRP is present and blocks the receptor of the anorexigenic pathway so MSH cannot attach to it Energetic PPT 4 (2/19/2016) Slide 2: Figure 23.1- Functions of Adipose Tissue • Adipose tissue produces hormones like leptin that signals long-term energy status • Produces eicosanoids, complement factors, growth factors, cytokines, enzymes/proteins • Overall: Adipose tissue has other functions than just storing energy Slide 3: Figure 23.1- Weight Categories • Children: Based on percentiles -‐ Problem because percentiles can change -‐ Because children’s weights have been increasing à Percentiles have incthased -‐ <5 percentile = Underweight -‐ 5 -84 percentile = Healthy -‐ 85 -94 percentile = Overweight th -‐ >/= 95 percentile = Obese • Adults: Based on BMI -‐ Absolute ranges -‐ Not a good indicator of how healthy a person is because composition not taken into account -‐ <18.5 kg/m = Underweight 2 -‐ 18.5-24.9 kg/m = Healthy -‐ 25-29.9 kg/m = Overweight -‐ 30-34.9 kg/m = Obese class I 2 -‐ 35-39.9 kg/m = Obese class II -‐ >/= 40 kg/m = Obese class III
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