Cellular Respira,on: Harvesng Chemical Energy Is To Make ATP

Chapter 9What’s thepoint?Cellular Respira,on:Harves,ng ChemicalEnergyThe pointis to makeATP!ATP2006-2007Principles of Energy HarvestHarves ng stored energy Glucose is the model– catabolism of glucose to produce ATP Cellularrespiration Catabolic pathwayFermenta onRespira onC6H12O6 6O2--- 6CO2 6H2O E (ATP heat)glucose oxygen energy water carbondioxideC6H12O6 6O2 ATP 6H2O 6CO2 heatCOMBUSTION making a lot of heat energy RESPIRATION making ATP (& some heat)by burning fuels in many small stepsby burning fuels in one stepATPenzymesO2fuel(carbohydrates)How do we harvest energy from fuels? Digest large molecules into smaller ones as electrons move they “carry energy” with them that energy is stored in another bond,released as heat or harvested to make ATPgains e- oxidized e-e-How do we move electrons in biology?– electrons cannot move alone in cells electrons move as part of H atom move H move electronsloses e-gains e-–e-reductionredoxoxidized reduced oxidationCO2 H2O heat Moving electrons in living systems– break bonds & move electrons from one moleculeto anotherloses e-ATPO2CO2 H2O ATP ( heat)glucoseoxidationepreduced –HreductionHoxidationC6H12O6 6O2H e- 6CO2 6H2O ATPreduction1

Coupling oxida on & reduc onOxida on & reduc on REDOX reac ons in respira on Oxida on– release energy as breakdown organic molecules break C-C bonds strip off electrons from C-H bonds by removing H atoms– C6H12O6 CO2 the fuel has been oxidized electrons aYracted to more electronega ve atoms– in biology, the most electronega ve atom?– O2 H2O oxygen has been reducedO– couple REDOX reac ons &use the released energy to synthesize ATP2– removing O– adding H– gain of electrons– stores energy– endergonicoxidationoxidationC6H12O6 6O2 Reduc on– adding O– removing H– loss of electrons– releases energy– exergonicC6H12O6 6O2 6CO2 6H2O ATP 6CO2 6H2O ATPreductionreductionlike in the bankMoving electrons in respira on Electron carriers move electrons byshuYling H atoms around– NAD NADH (reduced)– FAD 2 FADH2 (reduced)NAD nicotinamideVitamin B3niacinO–O– Pphosphates–OCN OO–O– P–OOH HNH2HOCN reductionoxidationO–O– P–Ocarries electrons asa reduced molecule–O NAD (nico namideadenine dinucleo de) Removes electrons fromfood (series of reac ons) NAD is reduced toNADH Enzyme ac on:dehydrogenase Oxygen is the eventual eacceptorOElectron transport chains Electron carrier molecules(membrane proteins) ShuYles electrons that releaseenergy used to make ATP Sequence of reac ons thatprevents energy release in 1explosive step Electron route:food--- NADH --- electron transport chain --- oxygenNH2How efficient!Build once,use many waysOO–O– Padenineribose sugarreducing power!NADHOHOxidizing agent in respira onCellular respira on: overview (anaerobic) 1.Glycolysis: cytosol; degradesglucose into pyruvate (aerobic) Pyruvate oxida on 2.Kreb’s Cycle: mitochondrialmatrix; pyruvate into carbondioxide 3.Electron Transport Chain:inner membrane ofmitochondrion; electronspassed to oxygen2

GlycolysisWhat’s thepoint? Breaking down glucose– “glyco – lysis” (splifng sugar)In thecytosol?Why doesthat makeevolutionarysense?glucose pyruvate2x 3C6CThe pointis to makeATP!– ancient pathway which harvests energy where energy transfer first evolved transfer energy from organic molecules to ATP s ll is star ng point for ALL cellular respira onATP– but it’s inefficient generate only 2 ATP for every 1 glucose2006-2007Evolu onary perspec ve Prokaryotes– first cells had no organellesEnzymesof glycolysis are“well-conserved” Anaerobic atmosphere– life on Earth first evolved without free oxygen (O2) inatmosphere– energy had to be captured from organic molecules inabsence of O2 Prokaryotes that evolved glycolysis are ancestors of allmodern life– ALL cells s ll u lize glycolysisYou meanwe’re related?Do I have to invitethem over forthe holidays?Glycolysis summaryendergonicinvest some ATPENERGY INVESTMENTENERGY PAYOFFexergonicharvest a little4 ATPATP & a little NADHlike in thebankNET YIELDThat’s not enoughATP for me!glucoseC-C-C-C-C-COverviewenzyme10 reac ons– convertglucose (6C) to2 pyruvate (3C)– produces:4 ATP & 2 NADH– consumes:2 ATP– net yield:2 ATP & 2 NADHnet yieldü2 ATPü2 ymeenzymeenzymeDHAPP-C-C-CG3PC-C-C-P22H2Pi enzymeNAD 2enzyme42PiADPenzymepyruvate 4C-C-CDHAP dihydroxyacetone phosphateG3P glyceraldehyde-3-phosphateATPSubstrate-level Phosphoryla on In the last steps of glycolysis, where did the Pcome from to make ATP?– the sugar substrate (PEP)-2 ATPG3PC-C-C-P– occurs in cytosolP is transferredfrom PEP to ADPükinase enzymeüADP ATPATP9enolaseH2OH2OPhosphoenolpyruvate Phosphoenolpyruvate(PEP)(PEP)ADP10pyruvate kinaseATPPyruvatePyruvateADPATPOCOC OCH2POCOC OCH3I get it!The Pi camedirectly fromthe substrate!3

Energy accoun ng of glycolysis2 ATPIs that all there is?2 ADPglucose pyruvate6C Not a lot of energy – for 1 billon years this is how life on Earthsurvived2x 3C4 ADP4 ATP2 NAD 2 no O2 slow growth, slow reproduc on only harvest 3.5% of energy stored in glucoseAll that work!And that’s allI get?– some energy investment (-2 ATP)– small energy return (4 ATP 2 NADH)O2O2But can’t stop there!DHAPNAD PiPiNAD NADHNADH 1,3-BPGHow is NADH recycled to NAD ?G3P6PiPiNAD NAD NADHNADH1,3-BPG7ADPGlycolysisADPAnother moleculemust accept H fromNADHH2OATPATP3-Phosphoglycerate(3PG)glucose 2ADP 2Pi 2 NAD 2 pyruvate 2ATP 2PG) Going to run out of NAD – without regenera ng NAD ,energy produc on would stop!– another molecule must accept Hfrom NADH soNAD H2O2CNAD 1Cback to glycolysis § Animals, some fungipyruvate lactic acidNADHwithout oxygenaerobic respirationanaerobic D NADHacetyl-CoACO2NADH3CNAD back to glycolysis acetaldehydeNADHNAD NAD lactatelactic acidfermentationwhich path youuse dependson who youare KrebscycleethanolalcoholfermentationAlcohol Fermenta onpyruvate ethanol CO2pyruvate ethanol Hwith oxygenH2OATP Bacteria, yeast§ beer, wine, bread2-Phosphoglycerate(2PG)10Fermenta on (anaerobic)NADH9Phosphoenolpyruvate(PEP)ADPis freed up for another round3CHard wayto makea living!O2 1 6C sugar 2 3C sugarsraw materials productsglucose pyruvate2x 3C6CO2O2Butglucose hasso much moreto give! Net gain 2 ATP 2 NADH– more carbons to strip off more energy to harvest3CNADH2C1CbacteriayeastrecycleNADHNAD back to glycolysis § Dead endprocess§ at 12%ethanol, killsyeast§ can’t reverse thereactionCount thecarbons!§ cheese, anaerobic exercise (no O2)4

animalssome fungiLac c Acid Fermenta onpyruvate lactic acid 3CNADHrecycleNADHO2Pyruvate is a branching pointPyruvate3CNAD back to glycolysis O2§ Reversible riaKrebs cycleaerobic respiration§ once O2 isavailable, lactate isconverted back topyruvate by theliverCount thecarbons!Glycolysis is only the startOxida on of pyruvate Glycolysis Pyruvate enters mitochondrial matrixglucose pyruvate6C2x 3C Pyruvate has more energy to yield– 3 more C to strip off (to oxidize)– if O2 is available, pyruvate enters mitochondria– enzymes of Krebs cycle complete the full oxida on ofsugar to CO2pyruvate CO23C1CKrebs cycle[––––NADCount the carbons!pyruvate aka Citric Acid Cycle each catalyzed by specific enzyme step-wise catabolism of 6C citrate moleculeWheredoes theCO2 go?Exhale!3 step oxida on processreleases 2 CO2 (count the carbons!)reduces 2 NAD 2 NADH (moves e-)produces 2 acetyl CoA Acetyl CoA enters Krebs cycle1937 1953– in mitochondrial matrix– 8 step pathway]2x pyruvate acetyl CoA CO23C2C1C3C2C6C4CHans Krebs1900-1981 Evolved later than glycolysis– does that make evolu onary sense? bacteria 3.5 billion years ago (glycolysis) free O2 2.7 billion years ago (photosynthesis) eukaryotes 1.5 billion years ago (aerobic respira on organelles mitochondria)This happenstwice for eachglucosemolecule4Cacetyl CoAcitrateoxidationof sugarsCO2x24C4C6C5C4CCO25

Count the electron carriers!pyruvate3C4CNADHcitratereductionof electroncarriers6Cx25C4CFADH2CO2acetyl CoA6C4CNADHThis happenstwice for eachglucosemolecule2C4CCO2CO24CATPNADHNADHElectron Carriers Hydrogen CarriersH § Krebs cycleH produces largequantities ofelectron carriers H H H H H H Whassup?So we fullyoxidizedglucoseC6H12O6 CO2& ended upwith 4 ATP!What’s thepoint?Energy accoun ng of Krebs cycle4 NAD 1 FADADP PiNADHu FADH2u go to ElectronTransportChain!2x pyruvate CO2ATPu4 NADH 1 FADH2H 3C3x 1C1 ADP1 ATPATPNet gain 2 ATP 8 NADH 2 FADH2What’s soimportant aboutelectron carriers?Value of Krebs cycle? If the yield is only 2 ATP then how was the Krebs cyclean adapta on?– value of NADH & FADH2 electron carriers & H carriers– reduced molecules move electrons– reduced molecules move H ions to be used in the Electron Transport Chainlike in thebankKreb’s Cycle: review If molecular oxygen is present . Each pyruvate is converted intoacetyl CoA (begin w/ 2):CO2 is released;NAD --- NADH;coenzyme A(from B vitamin),makesmolecule very reac ve From this point, each turn 2 C atomsenter (pyruvate) and 2 exit (carbondioxide) Oxaloacetate is regenerated (the“cycle”) For each pyruvate that enters: 3NAD reduced to NADH; 1 FAD reduced to FADH2; 1 ATP molecule6

ATP accoun ng so far There is a beYer way! Glycolysis 2 ATP Kreb’s cycle 2 ATP Life takes a lot of energy to run, need toextract more energy than 4 ATP!There’s got to be a better way!I need a lotmore ATP! Electron Transport Chain– series of proteins built intoinner mitochondrial membrane along cristae transport proteins & enzymes– transport of electrons down ETC linked to pumpingof H to create H gradient– yields 34-36 ATP from 1 glucose!– only in presence of O2 (aerobic respira on)Thatsounds morelike it!A working muscle recyclesover10 million ATPs per secondRemember the Electron Carriers?GlycolysisglucoseKrebs cycleG3PElectron Transport Chain8 NADH2 FADH2Building proton gradient!NADH NAD Hep2 NADHintermembranespaceH H H H e- H innermitochondrialmembraneCe–Qe–Time tobreak openthe piggybank!O2NADH HFADH2NAD NADHdehydrogenasee–HFAD2H 1O22cytochromebc complexH2Ocytochrome coxidase complexmitochondrialmatrixWhat powers the proton (H ) pumps? Electron Transport ChainInnermitochondrialmembraneIntermembrane spaceCcytochromebc complexMitochondrial matrix Electron carriers pass electrons & H to ETC– H cleaved off NADH & FADH2– electrons stripped from H atoms H (protons) electrons passed from one electron carrier to next in mitochondrialmembrane (ETC) flowing electrons energy to do work– transport proteins in membrane pump H (protons) acrossinner membrane to intermembrane spaceQNADHdehydrogenaseStripping H from Electron Carrierscytochrome coxidase complexTA-DA!!Moving electronsdo the work! HH HH H HH H H H H H H H Ce–NADHQe–FADH2FADNAD NADHdehydrogenasee–12H 2 O2cytochromebc complexH2Ocytochrome coxidase complexADP PiATPH 7