Y khoa, y dược - Nutrition, metabolism, and body temperature regulation: Part B

24 Nutrition, Metabolism, and Body Temperature Regulation: Part BProtein MetabolismWhen dietary protein is in excess, amino acids areOxidized for energy Converted into fat for storageOxidation of Amino AcidsFirst deaminated; then converted intoPyruvic acid A keto acid intermediate of the Krebs cycle Events include transamination, oxidative deamination, and keto acid modificationFigure 24.16Krebscycle OxidativedeaminationTransaminationAmino acid + Keto acid(a-keto-glutaric acid)Keto acid + Amino acid (glutamic acid)Keto acidmodificationModifiedketo acidEnter Krebscycle in body cellsLiverKidneyBlood During transamination an amine group is switched from an amino acid to a keto acid. During ketoacid modification the keto acids formed during transamination are altered so they can easily enter the Krebs cycle pathways.NH3 (ammonia)UreaUrea In oxidative deamination, the amine group of glutamic acid is removed as ammonia and combined with CO2to form urea. CO2123Excreted in urineProtein SynthesisIs hormonally controlled Requires a complete set of amino acids Essential amino acids must be provided in the dietCatabolic-Anabolic Steady StateA dynamic state in whichOrganic molecules (except DNA) are continuously broken down and rebuiltOrgans have different fuel preferencesNutrient PoolsThree interconvertible poolsAmino acidsCarbohydrates FatsAmino Acid PoolBody’s total supply of free amino acidsSource for Resynthesizing body proteins Forming amino acid derivativesGluconeogenesisFigure 24.17Pool ofcarbohydrates and fats(carbohydrates fats)Dietary proteinsand amino acidsFood intakeSome lost via cellsloughing, hair lossExcretedin urine Some lost via surfacesecretion, cell sloughingExcretedvia lungs Dietary carbohydratesand lipidsUreaComponentsof structural and functionalproteinsNitrogen-containingderivatives(e.g., hormones,neurotransmitters)Structuralcomponents of cells (membranes,etc.)Specialized derivatives(e.g., steroids, acetylcholine); bile saltsCatabolizedfor energyStorageformsPool of freeamino acidsNH3CO2Carbohydrate and Fat PoolsEasily interconverted through key intermediatesDiffer from the amino acid pool in that:Fats and carbohydrates are oxidized directly to produce energyExcess carbohydrate and fat can be storedFigure 24.18ProteinsProteinsCarbohydratesFatsExcretedin urineGlycogenGlucoseGlucose-6-phosphateGlyceraldehyde phosphatePyruvic acidAcetyl CoAAmino acidsKeto acidsTriglycerides (neutral fats)Lactic acidKetonebodiesGlycerol and fatty acidsNH3Krebscycle UreaAbsorptive and Postabsorptive StatesAbsorptive (fed) stateDuring and shortly after eatingAbsorption of nutrients is occurringPostabsorptive (fasting) stateWhen the GI tract is empty Energy sources are supplied by breakdown of reservesAbsorptive StateAnabolism exceeds catabolismCarbohydratesGlucose is the major energy fuel Glucose is converted to glycogen or fatAbsorptive StateFatsLipoprotein lipase hydrolyzes lipids of chylomicrons in muscle and fat tissuesMost glycerol and fatty acids are converted to triglycerides for storageTriglycerides are used by adipose tissue, liver, and skeletal and cardiac muscle as a primary energy sourceAbsorptive StateProteinsExcess amino acids are deaminated and used for ATP synthesis or stored as fat in the liverMost amino acids are used in protein synthesisFigure 24.19a(a) Major events of the absorptive stateMajor energy fuel:glucose (dietary)Liver metabolism:amino acids deaminated and used for energy or stored as fatMajor metabolic thrust:anabolism and energy storageAminoacidsProteinsGlycogenGlucoseGlucoseAmino acidsKeto acidsFatsCO2 + H2O +TriglyceridesGlycerol andfatty acidsCO2 + H2O+Figure 24.19b(b) Principal pathways of the absorptive stateAmino acidsProteinKetoacidsFatsFatsFatsGlucoseGlycogenGlycogenProteinGlucoseGlucoseGastrointestinaltractIn liver:In all tissues:In adiposetissue:GlucoseFattyacidsFattyacidsGlyceraldehyde-phosphateGlycerolGlycerolFattyacidsIn muscle:CO2 + H2O+CO2 + H2O+Absorptive State: Hormonal ControlInsulin secretion is stimulated byElevated blood levels of glucose and amino acidsGIP and parasympathetic stimulationInsulin Effects on MetabolismInsulin, a hypoglycemic hormone, enhancesFacilitated diffusion of glucose into muscle and adipose cells Glucose oxidationGlycogen and triglyceride formationActive transport of amino acids into tissue cellsProtein synthesis Figure 24.20StimulatesTargets tissue cells Beta cells ofpancreatic isletsBlood glucoseBlood insulinActive transportof amino acidsinto tissue cellsFacilitated diffusionof glucose intotissue cells Protein synthesisCellularrespirationEnhances glucoseconversion to:CO2 + H2O+ Fatty acids+glycerolGlycogenInitial stimulusPhysiological responseResultPostabsorptive StateCatabolism of fat, glycogen, and proteins exceeds anabolismGoal is to maintain blood glucose between mealsMakes glucose available to the bloodPromotes use of fats for energy (glucose sparing)Sources of Blood GlucoseGlycogenolysis in the liverGlycogenolysis in skeletal muscleLipolysis in adipose tissues and the liverGlycerol is used for gluconeogenesis in the liverSources of Blood GlucoseCatabolism of cellular protein during prolonged fastingAmino acids are deaminated and used for gluconeogenesis in the liver and (later) in the kidneysFigure 24.21a(a) Major events of the postabsorptive stateMajor energy fuels:glucose provided by glycogenolysis and gluconeogenesis, fatty acids, and ketonesLiver metabolism:amino acids converted to glucoseMajor metabolic thrust:catabolism and replacement of fuels in bloodAminoacidsProteinsGlycogenGlucoseFatty acidsand ketonesGlucoseAmino acidsKeto acidsGlucoseTriglyceridesGlycerol andfatty acidsCO2 + H2O+Figure 24.21b(b) Principal pathways of the postabsorptive stateAmino acidsAmino acidsFatty acidsGlycerolFattyacids +glycerolKetonebodiesBlood glucoseGlucoseKetoacidsKeto acidsStoredglycogenGlycogenProteinPyruvic andlactic acidsFatFatPyruvic andlactic acidsIn nervoustissue:In liver:In most tissues:In adipose tissue:In muscle:CO2 + H2O+CO2 + H2O+CO2 + H2O+CO2 + H2O+1222333444Postabsorptive State: Hormonal Controls Glucagon release is stimulated byDeclining blood glucoseRising amino acid levels Effects of GlucagonGlucagon, a hyperglycemic hormone, promotesGlycogenolysis and gluconeogenesis in the liverLipolysis in adipose tissueModulation of glucose effects after a high-protein, low-carbohydrate mealFigure 24.22Plasma glucose(and rising amino acid levels)StimulatesPlasma glucagonPlasma fatty acidsLiverAlpha cells ofpancreatic isletsStimulatesglycogenolysisand gluconeogenesisNegative feedback:rising glucose levels shut off initial stimulusStimulatesfat breakdownReduces, inhibitsIncreases, stimulatesAdipose tissueInitial stimulusPhysiological responseResultFat used by tissue cells= glucose sparingPlasma glucose(and insulin)Postabsorptive State: Neural ControlsIn response to low plasma glucose, or during fight-or-flight or exercise, the sympathetic nervous system and epinephrine from the adrenal medulla promoteFat mobilizationGlycogenolysisMetabolic Role of the LiverHepatocytesProcess nearly every class of nutrientPlay a major role in regulating plasma cholesterol levelsStore vitamins and mineralsMetabolize alcohol, drugs, hormones, and bilirubinCholesterolStructural basis of bile salts, steroid hormones, and vitamin DMajor component of plasma membranesMakes up part of the hedgehog signaling molecule that directs embryonic developmentTransported in lipoprotein complexes containing triglycerides, phospholipids, cholesterol, and proteinLipoproteinsTypes of lipoproteinsHDLs (high-density lipoproteins)The highest protein contentLDLs (low-density lipoproteins)Cholesterol-richVLDLs (very low density lipoproteins)Mostly triglyceridesChylomicronsFigure 24.23TriglyceridePhospholipidCholesterolProtein2–7%1–2%ChylomicronVLDLLDLHDL3–6%80–95%55–65%10%5%20%30%20%45–50%45%25%10–15%5–10%15–20%From intestineMade by liverReturned toliverLipoproteinsVLDLsTransport triglycerides to peripheral tissues (mostly adipose)LDLsTransport cholesterol to peripheral tissues for membranes, storage, or hormone synthesisHDLsTransport excess cholesterol from peripheral tissues to the liver to be broken down and secreted into bileAlso provide cholesterol to steroid-producing organs LipoproteinsHigh levels of HDL are thought to protect against heart attackHigh levels of LDL, especially lipoprotein (a) increase the risk of heart attackPlasma Cholesterol LevelsThe liver produces cholesterolAt a basal level regardless of dietary cholesterol intakeIn response to saturated fatty acidsPlasma Cholesterol LevelsSaturated fatty acidsStimulate liver synthesis of cholesterolInhibit cholesterol excretion from the bodyUnsaturated fatty acidsEnhance excretion of cholesterolPlasma Cholesterol LevelsTrans fatsIncrease LDLs and reduce HDLsPlasma Cholesterol LevelsUnsaturated omega-3 fatty acids (found in cold-water fish)Lower the proportions of saturated fats and cholesterolHave antiarrhythmic effects on the heartHelp prevent spontaneous clottingLower blood pressure Non-Dietary Factors Affecting CholesterolStress, cigarette smoking, and coffee lower HDL levelsAerobic exercise and estrogen increase HDL levels and decrease LDL levelsBody shape“Apple”: Fat carried on the upper body is correlated with high cholesterol and LDL levels “Pear”: Fat carried on the hips and thighs is correlated with lower cholesterol and LDL levels Energy BalanceBond energy released from food must equal the total energy output Energy intake = the energy liberated during food oxidationEnergy outputImmediately lost as heat (~60%)Used to do work (driven by ATP)Stored as fat or glycogenEnergy BalanceHeat energyCannot be used to do workWarms the tissues and bloodHelps maintain the homeostatic body temperatureAllows metabolic reactions to occur efficientlyObesityBody mass index (BMI) = wt (lb)  705/ht (inches)2Considered overweight if BMI is 25 to 30Considered obese if BMI is greater than 30Higher incidence of atherosclerosis, diabetes mellitus, hypertension, heart disease, and osteoarthritisBody Mass Index tableRegulation of Food IntakeTwo distinct sets of hypothalamic neuronsLHA neurons promote hunger when stimulated by neuropeptides (e.g., NPY)VMN neurons cause satiety through release of CRH when stimulated by appetite-suppressing peptides (e.g., POMC and CART peptides)Regulation of Food IntakeFactors that affect brain thermoreceptors and chemoreceptorsNeural signals from the digestive tractBloodborne signals related to body energy storesHormonesTo a lesser extent, body temperature and psychological factorsShort-Term Regulation of Food IntakeNeural signalsHigh protein content of meal increases and prolongs afferent vagal signalsDistension sends signals along the vagus nerve that suppress the hunger centerShort-Term Regulation of Food IntakeNutrient signalsIncreased nutrient levels in the blood depress eatingBlood glucoseAmino acids Fatty acids Short-Term Regulation of Food IntakeHormonesGut hormones (e.g., insulin and CCK) depress hungerGlucagon and epinephrine stimulate hungerGhrelin (Ghr) from the stomach stimulates appetite just before a mealLong-Term Regulation of Food IntakeLeptinHormone secreted by fat cells in response to increased body fat massIndicator of total energy stores in fat tissueProtects against weight loss in times of nutritional deprivationLong-Term Regulation of Food IntakeLeptinActs on the ARC neurons in the hypothalamusSuppresses the secretion of NPY, a potent appetite stimulantStimulates the expression of appetite suppressants (e.g., CART peptides)Figure 24.24Long-term controlsShort-term controlsHunger(appetiteenhancement)LHA(orexin-releasingneurons)Satiety(appetitesuppression)VMN(CRH-releasingneurons)ReleaseorexinsReleaseCRHReleasemelano-cortinsReleaseNPYARCnucleusNPY/AgRPgroupPOMC/CARTgroupInsulin(frompancreas)Leptin(from lipidstorage)SolitarynucleusStretch(distensionof GI tract)GlucoseAmino acidsFatty acidsGhrelinGlucagonEpinephrineGuthormonesand othersStimulatesInhibitsInsulinPYYCCKGuthormonesNutrientsignalsVagalafferentsHypothalamusBrain stemLong-Term Regulation of Food Intake Additional factorsTemperatureStressPsychological factorsAdenovirus infectionsSleep deprivationMetabolic RateTotal heat produced by chemical reactions and mechanical work of the bodyMeasured directly with a calorimeter or indirectly with a respirometerMetabolic RateBasal metabolic rate (BMR)Reflects the energy the body needs to perform its most essential activities Factors that Influence BMRAs the ratio of body surface area to volume increases, BMR increasesDecreases with ageIncreases with temperature or stressMales have a disproportionately higher BMRThyroxine increases oxygen consumption, cellular respiration, and BMRMetabolic RateTotal metabolic rate (TMR)Rate of kilocalorie consumption to fuel all ongoing activitiesIncreases with skeletal muscle activity and food ingestionRegulation of Body TemperatureBody temperature reflects the balance between heat production and heat lossAt rest, the liver, heart, brain, kidneys, and endocrine organs generate most heat During exercise, heat production from skeletal muscles increases dramatically Regulation of Body TemperatureNormal body temperature = 37C  5C (98.6F)Optimal enzyme activity occurs at this temperature Increased temperature denatures proteins and depresses neurons Figure 24.25• Basal metabolism• Muscular activity (shivering)• Thyroxine and epinephrine (stimulating effects on metabolic rate)• Temperature effect on cells• Radiation• Conduction/ convection• EvaporationHeat productionHeat lossCore and Shell TemperatureOrgans in the core have the highest temperatureBlood is the major agent of heat exchange between the core and the shellCore temperature is regulatedCore temperature remains relatively constant, while shell temperature fluctuates substantially (20C–40C)Mechanisms of Heat ExchangeFour mechanismsRadiation is the loss of heat in the form of infrared raysConduction is the transfer of heat by direct contactConvection is the transfer of heat to the surrounding airEvaporation is the heat loss due to the evaporation of water from body surfacesFigure 24.26Mechanisms of Heat ExchangeInsensible heat loss accompanies insensible water loss from lungs, oral mucosa, and skinEvaporative heat loss becomes sensible (active) when body temperature rises and sweating increases water vaporizationRole of the HypothalamusPreoptic region of the hypothalamus contains the two thermoregulatory centersHeat-loss centerHeat-promoting center Role of the HypothalamusThe hypothalamus receives afferent input fromPeripheral thermoreceptors in the skin Central thermoreceptors (some in the hypothalamus)Initiates appropriate heat-loss and heat-promoting activities Heat-Promoting MechanismsConstriction of cutaneous blood vesselsShiveringIncreased metabolic rate via epinephrine and norepinephrineEnhanced thyroxine releaseHeat-Promoting MechanismsVoluntary measures includePutting on more clothingDrinking hot fluidsChanging posture or increasing physical activityHeat-Loss MechanismsDilation of cutaneous blood vesselsEnhanced sweatingVoluntary measures includeReducing activity and seeking a cooler environmentWearing light-colored and loose-fitting clothingFigure 24.27, step 1Activates heat-loss center inhypothalamusSweat glands activated:secrete perspiration, which is vaporized by body heat, helping to cool the bodySkin blood vessels dilate: capillaries become flushed with warm blood; heat radiates from skin surfaceBody temperaturedecreases: bloodtemperature declines and hypothalamusheat-loss center“shuts off”StimulusIncreased bodytemperature; blood warmer than hypothalamic set pointFigure 24.27, step 2StimulusDecreased body tempera-ture; blood cooler thanhypothalamic set pointBody temperatureincreases: bloodtemperature rises and hypothalamusheat-promoting center “shuts off”Activates heat-promoting centerin hypothalamusSkeletal muscles activated when more heat must be generated; shivering beginsSkin blood vessels constrict:blood is diverted from skin capillaries and withdrawn to deeper tissues; minimizes overall heat loss from skin surfaceHomeostatic ImbalanceHyperthermiaElevated body temperature depresses the hypothalamusPositive-feedback mechanism (heat stroke) begins at core temperature of 41CCan be fatal if not correctedHomeostatic ImbalanceHeat exhaustionHeat-associated collapse after vigorous exerciseDue to dehydration and low blood pressureHeat-loss mechanisms are still functionalMay progress to heat stroke Homeostatic ImbalanceHypothermiaLow body temperature where vital signs decreaseShivering stops at core temperature of 30 - 32CCan progress to coma a death by cardiac arrest at ~ 21CFeverControlled hyperthermiaDue to infection (also cancer, allergies, or CNS injuries)Macrophages release interleukins (“pyrogens”) that cause the release of prostaglandins from the hypothalamusFeverProstaglandins reset the hypothalamic thermostat higherNatural body defenses or antibiotics reverse the disease process; cryogens (e.g., vasopressin) reset the thermostat to a lower (normal) levelDevelopmental AspectsLack of proteins in utero and in the first three years  mental deficits and learning disordersInsulin-dependent diabetes mellitus and genetic disorders  metabolic problems in childrenNon-insulin–dependent diabetes mellitus may occur in middle and old age, especially in obese peopleMetabolic rate declines throughout the life spanDevelopmental AspectsMany medications for age-related problems influence nutrition:Diuretics for heart failure and hypertension increase the risk of hypokalemiaSome antibiotics interfere with digestion and absorptionMineral oil (laxative) decrease absorption of fat-soluble vitaminsExcessive alcohol consumption may lead to malabsorption, vitamin and mineral deficiencies, deranged metabolism, damage to liver and pancreasDevelopmental AspectsNonenzymatic binding of glucose to proteins increases with age, leading to lens clouding and general tissue stiffening