Section 4. Fuel oxidation, generation of ATPFuel oxidation overview - respirationRespiration occurs in mitochondriaGlucose is universal fuel for every cellChapt. 19 Cellular bioenergetics of ATP, O2Fuel oxidation makes ATPATPThermodynamics briefSlide 9C. Exogonic, endogonic reactionsIII. Energy transformation for mechanical workATP powers transportIII. ATP powers biochemical workActivated intermediates in glycogen synthesisDG depends on substrate, product concentrationsActivated intermediates with ~bondsV. Energy from fuel oxidationOxidation/reductionRedox potentialsCalorie content of fuels reflects oxidation stateAnaerobic glycolysis” = fermentationOxidation not for ATP generationVII Energy balanceEnergy balanceSection 4. Fuel oxidation, generation of ATPFig.iv.1Section 4. Overview of Fuel oxidation, ATP generation:Physiological processes require energy transfer from chemical bonds in food:•Electrochemical gradient•Movement of muscle•Biosynthesis of complex molecules3 phases:•Oxidation of fuels (carbs, fats, protein)•Conversion of energy to ~PO4 of ATP•Utilization of ATP to drive energy-requiring reactionsFuel oxidation overview - respirationPhase 1: energy (e- ) from fuel transfer to NAD+ and FAD;Acetyl CoA, TCA intermediates are central compounds Phase 2: electron transport chain convert e- to ATP;membrane proton gradient drives ATP synthasePhase 3: ATP powers processesFig. iv.2Respiration occurs in mitochondriaFig. iv.3Respiration occurs in mitochondria:•Most enzymes in matrix•Inner surface has• e- transport chain•ATP synthase•ATP transported through inner membrane, diffuses through outer•Some enzymes encoded by mitochondrion genome, •most by nuclear genesGlucose is universal fuel for every cellFig. iv.4Glycolysis is universal fuel:1 glucose -> 2 pyruvate + 2 NADH + 2 ATP•Aerobic path:•Continued oxidation•Acetyl CoA -> TCA, •NADH, FAD(2H) -> e- transport chain•Lots of ATP•Anaerobic: fermentation:•‘anaerobic glycolysis’•Oxidation of NADH to NAD+•Wasteful reduction of pyruvate•to lactate in muscles•to ethanol, CO2 by yeastChapt. 19 Cellular bioenergetics of ATP, O2Ch. 19 Cellular bioenergeticsStudent Learning Outcomes:•Explain the ATP-ADP cycle•Describe how chemical bond energy of fuels can do cellular work through ~PO4 bond of ATP•Explain how NADH, FAD(2H) coenzymes carry electrons to electron transport chain• Describe how ATP synthesis is endergonic (requires energy)• Describe how ATP hydrolysis (exergonic) powers biosynthesis, movement, transportFuel oxidation makes ATPFig. 19.1Cellular Bioenergetics of ATP and O2:•Chemical bond energy of fuels transforms to physiological responses necessary for life•Fuel oxidation generates ATP•ATP hydrolysis provides energy for most work•High energy bonds of ATP:•Energy currency of cellATPHigh energy phosphate bond of ATP:•Strained phosphoanhydride bond• G0’ -7.3 kcal/mol standard conditions•Hydrolysis of ATP to ADP + Pi transfers PO4 to metabolic intermediate or protein, for next stepFig. 19.2Thermodynamics briefThermodynamics states what is possible:G = change in Gibbs free energy of reaction: G = G0 + RT ln [P]/[S] (R = gas const; T = temp oK)GG at standard conditions of1 M substrate & product and proceeding to equilibrium)G0’ = G0 under standard conditions of [H2O] = 55.5 M, pH 7.0, and 25oC [37oC not much different]Concentrations of substrate(s) and products(s):At equilibrium, G = 0, thereforeG0’ = -RT lnKeq’ = -RT ln[P]/[S]Thermodynamics briefThermodynamics states what is possible:•Exergonic reactions give off energy (G0’ < 0)•typically catabolic•Endergonic reactions require energy (G0’ > 0)•typically anabolic •Unfavorable reactions are coupled to favorable reactions • Hydrolysis of ATP is very favorable• Additive G0’ values determine overall directionC. Exogonic, endogonic reactionsPhosphoglucomutase converts G6P to/from G1P:• G6P to glycolysis• G1P to glycogen synthesis• Equilibrium favors G6PExergonic reactions give off energy (DG0’ < 0)Endergonic reactions require energy (DG0’ > 0)Fig. 19.3III. Energy transformation for mechanical workATP hydrolysis can power muscle movement:• Myosin ATPase hydrolyzes ATP, changes shape•ADP form changes shape back, moves along• Actin was activated by Ca2+ Fig. 19.4ATP powers transportActive transport: ATP hydrolysis moves molecules:• Na+, K+ ATPase sets up ion gradient; bring in items• Vesicle ATPases pump protons into lysosome• Ca2+-ATPases pump Ca2+ into ER, out of cell Fig. 10.6III. ATP powers biochemical workATP powers biochemical work, synthesis:Anabolic paths require energy: Go’ additive• Couple synthesis to ATP hydrolysis:•Phosphoryl transfer reactions•Activated intermediateEx. Table 19.3: glucose + Pi -> glucose 6-P + H2O + 3.3 kcal/mol ATP + H2O -> ADP + Pi- 7.3 kcal/molSum: glucose + ATP -> glucose 6-P + ADP -4.0 Also Glucose -> G-1-P will be -2.35 kcal/mol overall: hydrolysis of ATP, through G-6-P to G-1-PActivated intermediates in glycogen synthesisGlycogen synthesis needs 3 ~P:•Phosphoryl transfer to G6P•Activated intermediate with UDP covalently linkedFig. 19.5Fig. 19.6G depends on substrate, product concentrationsG depends on substrate, product concentrationsG = G0 + RT ln [P]/[S]•Cells do not have 1M concentrations•High substrate can drive reactions with positive G0’•Low product (removal) can drive reactions with positive G0’• Ex., even though equilibrium (G0’= +1.6 kcal/mol)favors G6P: G1P in a ratio 94/6, • If G1P is being removed (as glycogen synthesis), then equilibrium shifts ex. If ratio 94/3, then G = -0.41 favorableActivated intermediates with ~bondsOther compounds have high-energy bonds to aid biochemical work: (equivalent to ATP)•UTP, CTP and GTP also (made from ATP + NDP):•UTP for sugar biosyn, GTP for protein, CTP for lipids•Some other compounds:•Creatine PO4 energy reserve muscle, nerve, sperm•Glycolysis•Ac CoA TCA cycleFig. 19.7V. Energy from fuel oxidationFig. 19.8Energy transfer from fuels through oxidative phosphorylation in mitochondrion:•NADH, FAD(2H) transfer e- to O2•Stepwise process through protein carriers•Proton gradient created• e- to O2 -> H2O•ATP synthase makes ATP•lets in H+Oxidation/reductionFig. 19.9 NADHFig. 19.10FAD(2H)Oxidation: reduction