2 MetabolismMetabolism – process by which living systems acquire and use free energy to carry out vital processesCatabolism (degradation)Nutrients and cell constituents are broken down for salvage and/or generation of energyExergonic oxidationAnabolism (biosynthesis)Endergonic synthesis of biological molecules from simpler precursorsCoupled to exergonic processes through “high-energy” compounds
3 Role of Metabolism in Nutrition Definition: the sum of all biochemical changes that takeplace in a living organism.Group these reactions into two types:anabolic catabolicReactions: require energy release energyProduce: more complex more simple compoundscompoundsModusOperandi: Occurs in small steps, each of which is controlledby specific enzymes.
4 Relationship Between Catabolic and Anabolic Pathways Catabolic pathwaysComplex metabolites are transformed into simpler productsEnergy released is conserved by the synthesis of ATP or NADPHAnabolic pathwaysComplex metabolites are made from simple precursorsEnergy-rich molecules are used to promote these reactions
5 Examples of each type of metabolism: Anabolic Pathways Catabolic PathwaysProtein Biosynthesis GlycolysisGlycogenesis TCA (Krebs cycle)Gluconeogenesis ß-oxidationFatty Acid Synthesis Respiratory ChainOther useful generalizations:Some of the steps in the anabolic path (going “uphill”) may not beidentical to the catabolic path--but some are shared.ATPGeneratedProvidesEnergyFOR
6 Metabolism: Who Needs It? Average American consumes ~ 1450 lbs ( 600kg) of foodeach year.Assuming that 98.2% of this energy ismetabolizable, 1424 lbs ( 590kg) is used to supply ourneeds.Supplies roughly 1 x 106 kcals/ year
7 Energy needs Measurement of Energy Intake Diet Surveys Dietary and nutritional survey of British Adults (Gregory 1990)Average UK dietary energy intakeMen 10.2 MJ (2400 kcal/d)Women 7.02MJ (1650 kcal/d)
8 How do we employ energy?• MECHANICAL- muscle contraction• ELECTRICAL- maintaining ionic gradients(e.g., Na-K ATPase; 70% ofATP used by kidney & brainused to maintain gradient)• CHEMICAL- biotransformation ofmolecules (e.g., synthesisdegradation, metabolism)
9 International Unit of Energy: Joule : energy used when 1 Kg is moved1 meter by a force of 1 Newton: kJ = 103 J; MJ = 106 J: 1 kcal = kJ: Protein: 17 kJ or 4 kcal/gCHO: 17 kJ or 4 kcal/gFat: 37 kJ or 9 kcal/g
11 Energy needsMeasurement of Energy IntakeMetabolic Energy Yields
12 Average Energy Needs:European text: 100 kJ/ day x BW in kgor24 kcal/day x BW in kgAmerican Biochem text: kJ/ kg31-44 kcal/kg
13 Conversion Efficiency: Food to Usable Energy 40% used to makehigh energy phosphatebonds60% “lost” (?) asheat
14 How to measure energy in food Direct CalorimetryDirect measurement of heat producedBomb calorimeterCalculateCalories/g: 4 (cho), 9 (fat) ,4 (prt) and 7 (alcohol)based: lab analysis of food compositionCalorie chart or nutrient database
15 Energy needs Measurement of Energy Intake Bomb Calorimeter Food is ignited electrically in the presence of oxygenHeat of combustion is measured from a rise in water temperature
16 Bomb Calorimeter measures heat produced when food is burned
26 Energy needs Measurement of Energy Output Energy Output Energy of food ATP + Heat Loss50% efficiencyATP “Work “+ Heat Loss“Work “ Heat
27 Energy needs Measurement of Energy Output Energy Output Two methods direct calorimetryindirect calorimetryMeasurement of heatMeasurement ofenergy used
28 Energy needs Measurement of Energy Output direct calorimetry Measurement of heat loss
29 Energy needs Measurement of Energy Output Indirect calorimetry Utilisation of oxygenOxygen consumption is proportional to ATP synthesisUse oxygen consumption to determine heat production
30 Energy needs Measurement of Energy Output Indirect calorimetry Glucose oxidationStarch oxidation6H2O + 6CO 2C6H12O6 + 6O2+15.5 kJ/g of energy5nH2O + 6nCO 2(C6H12O5)n + 6nO2+17 kJ/g of energy
31 Energy needs Measurement of Energy Output Indirect calorimetry Fat oxidation(e.g. glyceryl butro-oleostearate (main fat in butter)C3H5O3.C4H7O.C18H33O. C18H35O+60O2++43CO240H2O39 kJ/g of energy
32 Energy needs Measurement of Energy Output Indirect calorimetry Respiratory quotient (RQ)CO 2 Produced / O 2 ConsumedRQ for Carbohydrates = 1.0RQ for fats = 0.71 (average)C6H12O6 + 6O26H2O + 6CO 2
33 Energy needs Indirect calorimetry Measurement of Energy Output RQ value can be used to find the amount energy produced per litre of oxygen consumedMetabolic mix
34 Energy needs Measurement of Energy Output Indirect calorimetry Respiratory Gas AnalysisRespirmetersDirect of measurement of O2 and CO2Heart Rate MonitoringHeart rate calibrated against oxygen utilisationIsotope MethodLabelled water (2H and 18O)Difference of rates of loss of isotopes loss of CO2
35 What are the components of energy expenditure? 1 : Basal metabolic rateDefinition:Determinants:Calculation:
36 Energy Out: Basal Metabolism Largest daily energy outputDefinition: “the sum total of minimal activity of all tissue cells of the body under steady sate conditions”Men estimate: lbs body weight X 11Women estimate: lbs body weight X 10affected byMuscle > Fat Male > FemaleYoung > OldTemperature: body and environment
37 Basal Metabolic RateBMR = number of calories would need daily simply to stay alive if were totally inactive, in bed, awake for 16 hours & slept for 8 hoursHarris-Benedict Equation:Women: 661+(4.38 x weight in pounds)+(4.38 x height in inches)-(4.7 x age)=BMRMen: 67+(6.24 x weight in pounds)+(12.7 x height in inches)- (6.9 x age)=BMR
42 2 : Energy Expenditure Component : THERMIC EFFECT OF FOODDefinition:Determinants:Contribution to Total Energy Expenditure:
43 2) Energy Out: Dietary Thermogenesis Energy to digest, absorb, metabolize foodAbout 10% of calories eaten
44 2) Thermic Effect of Food 3-6 hours following ingestion~10% energy intake2000 kcal diet = 200 kcal TEFAffected by:Meal size/frequencyComposition: Protein > Carbs/fatGenetics
45 3 : Components of Energy Expenditure Physical ActivityContribution to Total Expenditure:4 : What about accounting for changes in energy expendituredue to injury or trauma?
46 3) Energy Out: Physical Activity Physical Activity affected by:Intensity -- how vigorousTime spentBody weight
47 3) Physical Activity Variable: 20-40% Working muscles require energy Heart/lung extra energyAmt energy used depends on:Muscle massBody weightActivity nature & duration
48 Activity Level and Metabolism Activity can account for 20-30% of metabolismSedentary = Multiplier 1.15 x BMRLight activity (Normal Every day activities) = Multiplier 1.3 x BMRModerately Active(exercise 3-4 x’s week) = Multiplier 1.4 x BMRVery Active (exercise more than 4 x’s week) = Multiplier 1.5 x BMRExtremely Active (exercise 6-7 x’s week) = Multiplier 1.6 x BMR
49 Activity Level and Metabolism If you change Light activity (Normal Every day activities) to Moderately Active(exercise 3-4 x’s week) daily caloric burning goes up 7.7%If you change Light activity (Normal Every day activities) to Very Active (exercise more than 4 x’s week) daily caloric burning goes up 23%If you change Light activity (Normal Every day activities) to Extremely Active (exercise 6-7 x’s week) daily caloric burning goes up 38.5%
50 Who Are The Critically Ill? Full thicknessBurns trauma sepsisWho Are The Critically Ill?GI Cardiac Renal Cancer
51 Injury, Trauma, SurgeryNeurohormonal Activation of the StressResponseGlucocorticoid & CatecholamineActivation, Hi Glucagon:InsulinRatio, Growth Hormone ReleaseTachycardia, Tachypnea, Hyperglycemia,Mobilization of Body Fat, Massive Catabolismof Skeletal Muscle
52 Metabolism in critical injuries goes through at least three In Critical Illness, Timing of Assessment isExtremely Important!Why?????Metabolism in critical injuriesgoes through at least threedistinct phases:Ebb (1st 24 hrs post-injury)Flow (Days 2-5)Anabolic (7-10 days)
53 Nutrition Support in Stress Immediate Needs to Sustain Life:• Restore blood flow;• Maintain oxygen transport;• Prevent/treat infections.If malnourished, introduce nourishmentcautiously, if not--Refeeding syndrome: malabsorption, cardiacinsufficiency, respiratorydistress, CHF, etc.
54 Fuel Utilization in Maintenance and Injury Average Adult Composition % Maintaining Body Composition:Fuel Utilization in Maintenance and InjuryAverage Adult Composition%(w/w)WaterProtein 19Adipose Tissue 19CHO <1Inorganic matter 7
55 Recommended Fuel Sources (% of kcal)Source % of kcalsDRVs Atwater*FatProteinCHO*W.O. Atwater (1894), USDA Scientist credited with derivingphysiologic energy values of pro, CHO, fat.PROGRESS!!!
56 Fuel Sources During Exercise Normal ADL LIGHT MODERATE HEAVY
57 Energy Requirements Difficult to estimate Direct measurement ResearchEstimates from averagesBased on age/sexAssume light/moderate activityEstimate TEF
58 Energy We Need Energy for 3 Reasons: How many calories do you need? 1) Basal metabolism2) Physical activity3) Dietary thermogenesisHow many calories do you need?Simple calculation
59 1) Basal MetabolismDefinition: Energy required to maintain normal body functions while at restTo estimate the calories you need for basal metabolismFor men: Multiply body weight (lbs) by 11For women: Multiply body weight (lbs) by 108
60 2) Energy for Physical Activity ACTIVITY LEVELPERCENTAGE OF BASAL METABOLISM CALORIESInactive: sitting most of the day; <2 hours moving about slowly or standing30%Moderate: sitting most of the day; walking or standing 2-4 hours, no strenuous activity50%Active: physically active for >4 hours a day; little sitting or standing; some strenuous activity75%8
61 3) Dietary Thermogenesis Definition: the energy expended during digestion of foodIt accounts for approximately 10% of the body's total energy need (basal needs and energy needs)
62 Doing the CalculationJane weighs 140 and is moderately active student (she goes to classes and goes to the gym 1hr/day)Basal needs: 140 * 10 = 1400Physical activity needs: 1400 * .50= 700So far she needs 2100 calories, but wait, she has to digest!2100 * .10 = 210 caloriesNow, we add it up for her: = 2310 caloriesHow many calories do you need???8- Say: If I told you what a man or woman weighs and their level of physical activity you should be able to calculate how many calories they need for one day.
63 Energy Balance Balanced energy intake: not losing or gaining weight Negative energy balance (weight loss): energy intake < energy expendedPositive energy balance (weight gain): energy intake > energy expended8
64 Hunger vs. AppetiteHunger: physical need for energy, accompanied with unpleasant symptoms such as weakness, stomach pains, irritabilityAppetite: desire to eat is driven by mental stimuli
65 Obesity By culture By science How do we define obesity? 9 -Say can we really separate culture and science? Not entirely, no. Researchers and anyone in the health field will apply their own societal beliefs to what defines obesity and health consequences thereof. Consider an individual who weighs 400 pounds and undergoes stomach stapling. Now, from a medical perspective that may reduce her risk of disease, but a physician from another culture may say that that is a far too invasive procedure and will harm that individual’s mental health.
66 Is Obesity an Epidemic?Prevalence in US: 33% of adults and 25% of children are obese (But according to whom????)Risks associated with obesity: diabetes, hypertension, stroke, heart disease, elevated total cholesterol, low HDL-cholesterol, certain types of cancer, gallbladder disease9-Is obesity itself an epidemic or have Americans developed some unhealthy behaviors over the years? Ask them what they think about this-Focusing just on the obesity will be a waste of time, because people have a very, very hard time losing weight. Diets have a 95% failure rate. We are very, very far from drug that can reduce obesity over the long term without a lot of side effects. Not a solution for the general public.-What about the fact that people come in all shapes and sizes? People should come in all shapes and sizes. But there’s a balance between accepting people of all sizes and encouraging weight control.-can talk about my research with diabetes-we can not underestimate the emotional damage, I.e. poor self esteem, depression, that accompanies obesity, but again, this is a cultural facor and the others are actual risks.
67 What Causes Obesity3 major factors contribute to the development of obesity1) Genetic backgroundHeredity may account for approx % of obesity but this is very poorly understoodEffects on metabolism (rare); traits that predispose (common)2) Dietary intake3) Physical activity9-Explain that I disagree with the genetic background one; eating behaviors will outweigh genes. Plus, you really can't do anything about genes. All the work that's being done is being done with rats. We are a very long way off from treating genetic traits of obesity, and I'm not convinced that this will ever be sucessful. You have to take in more calories than you expend, that is the one machine like trait of humans. We run on fuel and when we get extra we store it, and when we don't get enough, we burn it. That doesn't mean that all obese people overeat, because their energy output may be very slow.
68 Measuring Body Fatness Weight-for-Height tables:Dietary Guidelines for AmericansMetropolitan Life Insurance Company (allows for increased weight with age)Limitations: not based on percentage body fatBody Mass Index (BMI)- widely usedCalculated by dividing body weight (in kg) by height (in meters) squared19-25 is considered acceptableoverweight is btw> 30 obesity9-Photocopy table 9.1 and show as an example of a weight for height table. Say, really not very accurate-Photocopy Met. Life. Ins. table and show-Say about BMI: You will see this more and more. It has become the more accepted standard for obesity assessment. Note: individual's with BMI's over 30 are necessarily at risk for disease. Many other factors are important, like physical activity levels, smoking, stress, diet, alcohol intake, heredity factors
69 Some Methods for Assessing Body Fat: Scale weighing doesn't distinguish between lean body mass and body fatSkinfold thickness measurementsBioelectrical impedanceUnderwater weighingMagnetic resonance imaging (MRI)CAT scansUltrasoundTotal body electrical conductivityMagnetic resonance spectroscopy9-Say: If you've considered getting any of these done, I would read more about them on page 9-6 of textbook.-Say about point one: You'll also see this method at gyms and sometimes at doctor's offices where calipers are used to measure body fatness in certain area's of the body. These really aren't too accurate because it is very difficult to take the reading correctly.
70 We Do Need Body Fat For survival we need: Low body fat associated with 3-5% for men10-12% for womenLow body fat associated withDelayed physical maturation during adolescenceInfertilityAccelerated bone lossSymptoms of starvation
71 Role of Body Fat: Makes hormones Component of every type of body cell Cushions internal organsThis fat is not available for energy
72 Location of Body Fat is Important to Health Central obesity is associated with more health risks than lower obesityAssessing Body Fat Distribution:Waist to hip ratioMore than .80 in women and .95 in men indicate central body fat distributionWaist circumferenceOver 40" (102 cm) in men (increased risk for health problems)Over 35" (88 cm) in women9-Show Illustration 9.2 and 9.3-Say: Picture 9.2 is silly but it has been found that central obesity, the apple shape, is associated with increased risk for diabetes, hypertension, high blood cholesterol, and heart disease-don't need to know the numbers but know that these two methods are commonly used to assess body fat distribution
73 Realities of ObesityMyth: any individual can get to any body weight if they diet and exercise enoughPeople do come in different shapes and sizes and people should come in different shapes and sizesFrom a health perspective, the goal of obesity prevention and treatment should be for people to eat a health promoting diet, get regular exercise, and pay attention to hunger and satiety cuesWhat are the barriers with this goal?????-but getting to this behavior modification therapy isn’t easy. What of these three factors, changing the diet, exercising, and eating less, do you think is most easily done? Exercise I think.
75 Body Weight Fat Mass + Fat Free Mass FFM: muscle, lean tissue, bone, waterDiseases associated with:Excessive fat massDepleted fat massDepleted FFM
76 Body Weight Body weight = Fat + FFM Healthy Body Weight Not % fat % FFMHealthy Body WeightWeight associated lowest mortalityTechniques for Assessing body weightLife Insurance TablesRelative weightBody Mass Index
77 Disadvantages relative weight Life Insurance TablesRarely used research/clinical practiceRelative weightActual weight/desirable weight%: overweight% obeseDisadvantages relative weightDesirable difficult to defineNot sex specificNot adjusted for age
78 Body Mass Index (BMI) X 705 Weight (kg) Weight (lb) BMI = Height (m2) World Health Organization, 1998Normal values 18.524.9 AverageOverweight 25Pre-obesity 2529.9 IncreasedObesity class I 30.034.9 ModerateObesity class II 35.039.9 HighObesity class III 40.0 Very HighWeight (kg)Height (m2)BMI =Weight (lb)Height (in2)X 705Classification BMI (kg/m2) Risk co-morbidity
81 SkinfoldMeasures subcutaneous fatAccuracy depends on caliper skill
82 Other High Tech Methods Bioelectrical Impedance BMIMagnetic Resonance Imaging MRI“Bod-Pod” measures air displacement
83 Bioelectrical Impedance Estimation of body compositionMost used in clinical practiceBased on electrical conduction through organismAt higher frequencies (eg 50 kHz) resistance of cell membranes reduced so that current penetrates both extra- and intracellular fluidsBio impedance is a reliable prediction of the body’s main conduction material : water73.2% FFM consists of water and total FM + FFM = total body weightElectrodes placed on dominant side of body; legs apart and not in contactMore accurate in obese women than DEXA
84 Fat intake but Overweight Total caloriesPhysical activity
85 1 lb (0.4kg) body fat =~ 3500 kcal Energy Balance Positive - Gain 1 lb - eat 3,500 kcal more than needNegative -Lose 1 lb - eat 3,500 kcal less than needIf energy bal = kcal / day /500 = 7 days to lose 1 lbBest to combine with physical activity, e.g., mile walk = kcal
86 What happens in weight loss? Water Fat Muscle massMay Bone densityGradual weight loss minimizes loss of muscle & boneDrastic methods: fasting, surgery, liposuctionOther methods: diets, pills
87 Body fat location is important Apple = AbdomenPear =Hips & thighsApple -> risk of heart diseasewaist/hip ratio:>0.8 F, > 0.95 Mindicates apple shape
88 Assessing obesity: bmi, waist circumference and disease risk Disease Risk Relative to Normal Weight and Waist CircumferenceMen <102 cm Women <88 cmMen >102 cm Women >88 cmCategoryBMIUnderweightNormal*OverweightObesityExtreme obesity<18.5>40—IncreasedHigh Very highExtremely high—HighVery high Very highExtremely high*An increased waist circumference can denote increased disease risk even in persons of normal weight.Adapted from Clinical guidelines. National Heart, Lung, and Blood Institute Web site. Available at: Accessed July 31, 1998.
89 Correlates with body fat content European Origin Asian: healthy weight <23.5Polynesian: healthy weightElderly: healthy weight up to 27Requires further researchNot suitable for athletes
90 Body Fat Distribution disease risk/mortality with excessive body fat ‘Healthy’ % body fat12-20% Men % WomenFat distribution associated disease riskAbdominal fat riskLower body fat: no increase risk
91 Central Obesity: Abdominal fat Measures of Central Adiposity prevalence Men, postmenopausal womenMeasures of Central Adiposity1) Waist Circumference> 88 cm women, 102cm men2) Waist:Hip Ratio>0.8 women, 0.95 men3) Fat fold measuresTraining required
109 OVERVIEW OF METABOLISM: Too Much, Too Little, Too StressedEnergy Economy in FeastingMetabolic Adaptation to Starvation• WHO Guidelines for Treatment of Severe MalnutritionFuel Utilization in Hypermetabolic States
110 Reclaiming Energy From Stored Fuel Sources: By Choice = Fasting By Necessity= StarvingExhaustion of “labile” CHO:Exhaustion of stored CHO:Problem: certain tissues require glucose for energyTapping into stored protein:Short-term effect and contribution:If this contribution continues:
111 Adaptation to Starvation/ Fasting Building glucose in the absence of labile or stored CHO:After deamination, the carbon skeletons of some amino acidscan be used to make glucose or ketone bodies (ketoacids).Gluconeogenesis: the formation of glucose from lactate,some amino acids, and glycerolLong-term dependence on GNG to fuel brain is not feasible.Switch to ketone production within 10 d of fast -- providesmajority of energy for brain. Protein sacrificed for glucoseproduction for parts of brain requiring it.
112 Benefits of Ketosis:• provides needed source of energy;• suppresses appetite.Concomitant Changes in Energy ExpenditureWasting results in decreased energy expenditureHeart mass Lung mass Skeletal muscleHormonal response to fasting leads to energy conservation
113 Metabolic Adaptations to Fasting/Starvation: ADVANTAGES & DISADVANTAGESAdvantages DisadvantagesEnergy Expenditure Wasting ofmuscle massBody Temperature DecreasedimmuneEnhanced Survival competence