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

24 Nutrition, Metabolism, and Body Temperature Regulation: Part ANutritionNutrient: a substance in food that promotes normal growth, maintenance, and repairMajor nutrientsCarbohydrates, lipids, and proteinsOther nutrients Vitamins and minerals (and, technically speaking, water)CarbohydratesDietary sourcesStarch (complex carbohydrates) in grains and vegetablesSugars in fruits, sugarcane, sugar beets, honey and milkInsoluble fiber: cellulose in vegetables; provides roughageSoluble fiber: pectin in apples and citrus fruits; reduces blood cholesterol levelsCarbohydratesUsesGlucose is the fuel used by cells to make ATPNeurons and RBCs rely almost entirely upon glucose Excess glucose is converted to glycogen or fat and storedLipidsDietary sourcesTriglyceridesSaturated fats in meat, dairy foods, and tropical oilsUnsaturated fats in seeds, nuts, olive oil, and most vegetable oilsCholesterol in egg yolk, meats, organ meats, shellfish, and milk productsLipidsEssential fatty acidsLinoleic and linolenic acid, found in most vegetable oilsMust be ingestedLipidsEssential uses of lipids in the bodyHelp absorb fat-soluble vitaminsMajor fuel of hepatocytes and skeletal musclePhospholipids are essential in myelin sheaths and all cell membranesLipidsFunctions of fatty deposits (adipose tissue)Protective cushions around body organsInsulating layer beneath the skinConcentrated source of energyProteinsDietary sourcesEggs, milk, fish, and most meats contain complete proteins Legumes, nuts, and cereals contain incomplete proteins (lack some essential amino acids)Legumes and cereals together contain all essential amino acids ProteinsUsesStructural materials: keratin, collagen, elastin, muscle proteinsMost functional molecules: enzymes, some hormones, antibodiesProteinsUse of amino acids in the bodyAll-or-none ruleAll amino acids needed must be present for protein synthesis to occurAdequacy of caloric intakeProtein will be used as fuel if there is insufficient carbohydrate or fat availableProteinsNitrogen balanceState where the rate of protein synthesis equals the rate of breakdown and lossPositive if synthesis exceeds breakdown (normal in children and tissue repair)Negative if breakdown exceeds synthesis (e.g., stress, burns, infection, or injury)ProteinsHormonal controlsAnabolic hormones (GH, sex hormones) accelerate protein synthesisFigure 24.2Corn andother grainsBeansand otherlegumesTryptophanMethionineValineThreoninePhenylalanineLeucineIsoleucineLysineVegetarian diets providing the eightessential amino acids for humans (b)Essential amino acids(a)ValineThreoninePhenylalanine(Tyrosine)LeucineIsoleucineLysineMethionine(Cysteine)TryptophanHistidine(Infants)Arginine(Infants)TotalproteinneedsVitaminsOrganic compounds Crucial in helping the body use nutrients Most function as coenzymesVitamins D, some B, and K are synthesized in the bodyVitaminsTwo types, based on solubilityWater-soluble vitaminsB complex and C are absorbed with waterB12 absorption requires intrinsic factorNot stored in the body VitaminsFat-soluble vitaminsA, D, E, and K are absorbed with lipid digestion productsStored in the body, except for vitamin KVitamins A, C, and E act as antioxidantsMineralsSeven required in moderate amounts:Calcium, phosphorus, potassium, sulfur, sodium, chloride, and magnesiumOthers required in trace amountsWork with nutrients to ensure proper body functioningUptake and excretion must be balanced to prevent toxic overloadMineralsExamplesCalcium, phosphorus, and magnesium salts harden boneIron is essential for oxygen binding to hemoglobinIodine is necessary for thyroid hormone synthesisSodium and chloride are major electrolytes in the blood MetabolismMetabolism: biochemical reactions inside cells involving nutrientsTwo types of reactionsAnabolism: synthesis of large molecules from small onesCatabolism: hydrolysis of complex structures to simpler onesMetabolismCellular respiration: catabolism of food fuels and capture of energy to form ATP in cellsEnzymes shift high-energy phosphate groups of ATP to other molecules (phosphorylation)Phosphorylated molecules are activated to perform cellular functionsStages of MetabolismProcessing of nutrientsDigestion, absorption and transport to tissuesCellular processing (in cytoplasm) Synthesis of lipids, proteins, and glycogen, orCatabolism (glycolysis) into intermediates Oxidative (mitochondrial) breakdown of intermediates into CO2, water, and ATPFigure 24.3Stage 1 Digestion in GI tract lumen to absorbable forms.Transport via blood totissue cells.Stage 2 Anabolism (incorporation into molecules) and catabolism of nutrients to form intermediates within tissue cells.Stage 3 Oxidative breakdown of products of stage 2 in mitochondria of tissue cells. CO2 is liberated, and H atoms removed are ultimately delivered to molecular oxygen, formingwater. Some energy released isused to form ATP.Catabolic reactionsAnabolic reactionsGlycogenPROTEINSProteinsFatsCARBOHYDRATESGlucoseFATSAmino acidsGlucose and other sugarsGlycerolFatty acidsPyruvic acidAcetyl CoAInfrequentCO2NH3HKrebscycle Oxidativephosphorylation(in electron transport chain)O2H2OOxidation-Reduction (Redox) ReactionsOxidation; gain of oxygen or loss of hydrogenOxidation-reduction (redox) reactionsOxidized substances lose electrons and energyReduced substances gain electrons and energyOxidation-Reduction (Redox) ReactionsCoenzymes act as hydrogen (or electron) acceptorsNicotinamide adenine dinucleotide (NAD+) Flavin adenine dinucleotide (FAD) ATP Synthesis Two mechanismsSubstrate-level phosphorylationOxidative phosphorylationSubstrate-Level PhosphorylationHigh-energy phosphate groups directly transferred from phosphorylated substrates to ADP Occurs in glycolysis and the Krebs cycleFigure 24.4aEnzymeCatalysisEnzyme(a) Substrate-level phosphorylationOxidative PhosphorylationChemiosmotic processCouples the movement of substances across a membrane to chemical reactionsOxidative PhosphorylationIn the mitochondriaCarried out by electron transport proteins Nutrient energy is used to create H+ gradient across mitochondrial membrane H+ flows through ATP synthaseEnergy is captured and attaches phosphate groups to ADP Figure 24.4bADP +MembraneHigh H+ concentration inintermembrane spaceLow H+ concentration in mitochondrial matrixEnergyfrom foodProtonpumps(electrontransportchain)ATPsynthase(b) Oxidative phosphorylationCarbohydrate MetabolismOxidation of glucose C6H12O6 + 6O2  6H2O + 6CO2 + 36 ATP + heatGlucose is catabolized in three pathwaysGlycolysisKrebs cycleElectron transport chain and oxidative phosphorylationFigure 24.5Via oxidativephosphorylationVia substrate-levelphosphorylationMitochondrionMitochondrialcristaeCytosolKrebscycleGlucoseGlycolysisPyruvicacidElectron transportchain and oxidativephosphorylationChemical energy (high-energy electrons)1 During glycolysis, each glucose molecule is broken down into two molecules of pyruvic acid in the cytosol.2 The pyruvic acid then enters the mitochondrial matrix, where the Krebs cycle decomposes it to CO2. During glycolysis and the Krebs cycle, small amounts of ATP are formed by substrate-level phosphorylation.3 Energy-rich electrons picked up bycoenzymes are transferred to the elec-tron transport chain, built into the cristae membrane. The electron transport chain carries out oxidative phosphorylation, which accounts for most of the ATP generated by cellular respiration.Chemical energyGlycolysis10-step pathwayAnaerobicOccurs in the cytosolGlucose  2 pyruvic acid moleculesThree major phasesSugar activationSugar cleavageSugar oxidation and ATP formationFigure 24.6 (3 of 3)To Krebscycle(aerobicpathway)224 ADP2 Lactic acid2 Pyruvic acidDihydroxyacetonephosphateGlyceraldehyde3-phosphatePhase 3Sugar oxidationand formationof ATPThe 3-carbon frag-ments are oxidized (by removal of hydrogen) and 4 ATP molecules are formedCarbon atomPhosphate2 NAD+2 NAD+NADH+H+NADH+H+GlycolysisElectron trans-port chain and oxidativephosphorylationKrebscycleGlycolysisFinal products of glycolysis 2 pyruvic acid Converted to lactic acid if O2 not readily availableEnter aerobic pathways if O2 is readily available2 NADH + H+ (reduced NAD+)Net gain of 2 ATP Krebs CycleOccurs in mitochondrial matrixFueled by pyruvic acid and fatty acidsKrebs CycleTransitional phaseEach pyruvic acid is converted to acetyl CoADecarboxylation: removal of 1 C to produce acetic acid and CO2Oxidation: H+ is removed from acetic acid and picked up by NAD+Acetic acid + coenzyme A forms acetyl CoA Krebs CycleCoenzyme A shuttles acetic acid to an enzyme of the Krebs cycleEach acetic acid is decarboxylated and oxidized, generating: 3 NADH + H+1 FADH22 CO21 ATPKrebs Cycle Does not directly use O2Breakdown products of fats and proteins can also enter the cycleCycle intermediates may be used as building materials for anabolic reactionsPLAYAnimation: Krebs CycleFigure 24.7Krebs cycleNAD+NAD+GDP +NAD+FADNAD+NADH+H+CytosolMitochondrion(matrix)NADH+H+FADH2NADH+H+Citric acid(initial reactant)Isocitric acidOxaloacetic acid (pickup molecule)Malic acidSuccinic acidSuccinyl-CoAGTPADPCarbon atomInorganic phosphateCoenzyme A Acetyl CoAPyruvic acid from glycolysisTransitionalphaseFumaric acidNADH+H+CO2CO2CO2-Ketoglutaric acidElectron trans-port chain and oxidativephosphorylationGlycolysisKrebscycleElectron Transport Chain and Oxidative PhosphorylationThe part of metabolism that directly uses oxygenChain of proteins bound to metal atoms (cofactors) on inner mitochondrial membraneSubstrates NADH + H+ and FADH2 deliver hydrogen atoms Electron Transport Chain and Oxidative PhosphorylationHydrogen atoms are split into H+ and electronsElectrons are shuttled along the inner mitochondrial membrane, losing energy at each stepReleased energy is used to pump H+ into the intermembrane spaceElectron Transport Chain and Oxidative PhosphorylationRespiratory enzyme complexes I, III, and IV pump H+ into the intermembrane space H+ diffuses back to the matrix via ATP synthase ATP synthase uses released energy to make ATPPLAYAnimation: Electron TransportFigure 24.8IntermembranespaceInnermitochondrialmembraneMitochondrialmatrixNADH + H+NAD+FAD(carryingfrom food)FADH2KrebscycleGlycolysisElectron transportchain and oxidativephosphorylationElectron Transport ChainChemiosmosisADP +2 H+ +Electrons are transferred from complex to complex and some of their energy is used to pump protons (H+) into the intermembrane space, creating a proton gradient.ATP synthesis is powered by the flow of H+ back across the inner mitochondrial membrane through ATP synthase.ATPsynthase12Electron Transport Chain and Oxidative PhosphorylationElectrons are delivered to O, forming O–O– attracts H+ to form H2OFigure 24.9GlycolysisKrebscycleElectron trans-port chain and oxidativephosphorylationEnzymeComplex IEnzymeComplex IIIEnzymeComplex IVEnzymeComplex IINADH+H+FADH2Free energy relative to O2 (kcal/mol)Electronic Energy GradientTransfer of energy from NADH + H+ and FADH2 to oxygen releases large amounts of energyThis energy is released in a stepwise manner through the electron transport chainATP SynthaseTwo major parts connected by a rod Rotor in the inner mitochondrial membraneKnob in the matrixWorks like an ion pump in reverseFigure 24.11Mitochondrial matrixIntermembrane spaceADP+A stator anchored in the membrane holds the knob stationary.As the rotor spins, a rod connecting the cylindrical rotor and knob also spins.The protruding, stationary knob contains three catalytic sites that join inorganic phosphate to ADP to make ATP when the rod is spinning.A rotor in the membrane spins clockwise when H+flows through it down the H+ gradient.Figure 24.12MitochondrionCytosol2AcetylCoAElectron transportchain and oxidativephosphorylationGlucoseGlycolysisPyruvicacidNet +2 ATPby substrate-levelphosphorylation+ about 28 ATPby oxidativephosphorylation+2 ATPby substrate-levelphosphorylationElectronshuttle across mitochondrialmembraneKrebscycle(4 ATP–2 ATPused foractivationenergy)2 NADH + H+2 NADH + H+6 NADH + H+2 FADH2About32 ATPMaximumATP yieldper glucose10 NADH + H+ x 2.5 ATP2 FADH2 x 1.5 ATPGlycogenesis and GlycogenolysisGlycogenesisGlycogen formation when glucose supplies exceed need for ATP synthesisMostly in liver and skeletal muscleGlycogenolysisGlycogen beakdown in response to low blood glucoseFigure 24.13Cell exteriorHexokinase(all tissue cells)Cell interiorMutaseGlycogenesisGlycogenolysis MutaseADPGlucose-6-phosphatase(present in liver,kidney, andintestinal cells)GlycogensynthaseGlycogenphosphorylasePyrophosphorylase2Blood glucoseGlucose-6-phosphateGlucose-1-phosphateGlycogenUridine diphosphateglucoseGluconeogenesisGlucose formation from noncarbohydrate (glycerol and amino acid) moleculesMainly in the liverProtects against damaging effects of hypoglycemia Lipid MetabolismFat catabolism yields 9 kcal per gram (vs 4 kcal per gram of carbohydrate or protein)Most products of fat digestion are transported as chylomicrons and are hydrolyzed by endothelial enzymes into fatty acids and glycerol Lipid MetabolismOnly triglycerides are routinely oxidized for energyThe two building blocks are oxidized separatelyGlycerol pathwayFatty acid pathwayLipid MetabolismGlycerol is converted to glyceraldehyde phosphateEnters the Krebs cycleEquivalent to 1/2 glucose Lipid MetabolismFatty acids undergo beta oxidation, which producesTwo-carbon acetic acid fragments, which enter the Krebs cycleReduced coenzymes, which enter the electron transport chainFigure 24.14Krebscycle GlycerolFatty acidsCoenzyme ALipaseb Oxidationin the mito-chondriaCleavageenzymesnips off2C fragmentsGlycolysisGlyceraldehydephosphate(a glycolysis intermediate)Pyruvic acidLipidsAcetyl CoAFADH2ONAD+NADH + H+FADH2Lipogenesis Triglyceride synthesis occurs when cellular ATP and glucose levels are highGlucose is easily converted into fat because acetyl CoA is An intermediate in glucose catabolism A starting point for fatty acid synthesis LipolysisThe reverse of lipogenesisOxaloacetic acid is necessary for complete oxidation of fatWithout it, acetyl CoA is converted by ketogenesis in the liver into ketone bodies (ketones)Figure 24.15ElectrontransportCholesterolStored fatsin adiposetissueDietary fatsGlycerolGlycolysisGlucoseGlyceraldehydephosphatePyruvic acidAcetyl CoACO2 + H2O+SteroidsBile saltsFatty acidsKetonebodiesTriglycerides(neutral fats)CertainaminoacidsKetogenesis (in liver)Catabolic reactionsAnabolic reactionsLipogenesisKrebscycle bSynthesis of Structural MaterialsPhospholipids for cell membranes and myelinCholesterol for cell membranes and steroid hormone synthesisIn the liver Synthesis of transport lipoproteins for cholesterol and fatsSynthesis of cholesterol from acetyl CoAUse of cholesterol to form bile salts