Mitochondria Cellular Respiration

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<ul><li><p>ATP</p></li><li><p>Overview of cellular respiration4 metabolic stagesAnaerobic respiration1. Glycolysisrespiration without O2in cytosolAerobic respirationrespiration using O2in mitochondria2. Pyruvate oxidation3. Krebs cycle4. Electron transport chain(+ heat)</p></li><li><p>What is Cellular Respiration?Step-by-step breakdown of high-energy glucose molecules to release energy Takes place day and night in all living cellsOccurs in stages, controlled by enzymes</p></li><li><p>1. Glycolysis (splitting of sugar) a. cytosol, just outside of mitochondria.Grooming Phase a. migration from cytosol to matrix.Krebs Cycle (Citric Acid Cycle) a. mitochondrial matrix4. Electron Transport Chain (ETC) and Oxidative Phosphorylationa. Also called Chemiosmosisb. inner mitochondrial membrane.</p><p>Breakdown of Cellular Respiration</p></li><li><p>ATP Energy Currency of CellsAn ATP molecule contains potential energy, much like a compressed spring. When a phosphate group is pulled away during a chemical reaction, energy is released. </p></li><li><p>This cycle is the fundamental mode of energy exchange in biological systems.ATP-ADP Cycle</p></li><li><p>ATP-ADP CycleATP is constantly recycled in your cells. A working muscle cell recycles all of its ATP molecules about once each minute. That's 10 million ATP molecules spent and regenerated per second! </p></li><li><p>Different types of Cellular RespirationAerobic respiration Occurs in the presence of oxygenWhen chemically breaking down glucose completely, this process releases large amounts energy- Releasing carbon dioxide and water as waste products.</p><p>Anaerobic respiration-Occurs if there is a lack of oxygen available for aerobic respiration-Only Glycolysis occurs-Glucose is incompletely broken down -In this type of respiration a lot less energy is -produced and most of it is lost as heat. </p></li><li><p>Glycolysis Breaking down glucose glyco lysis (splitting sugar)</p><p>ancient pathway which harvests energywhere energy transfer first evolvedtransfer energy from organic molecules to ATPstill is starting point for all cellular respirationbut its inefficient generate only 2 ATP for every 1 glucoseoccurs in cytosolIn the cytosol? Why does that make evolutionary sense?</p></li><li><p>Evolutionary perspectiveProkaryotesfirst cells had no organellesAnaerobic atmospherelife on Earth first evolved without free oxygen (O2) in atmosphereenergy had to be captured from organic molecules in absence of O2Prokaryotes that evolved glycolysis are ancestors of all modern lifeALL cells still utilize glycolysisYou mean were related? Do I have to invite them over for the holidays?</p></li><li><p>10 reactionsconvert glucose (6C) to 2 pyruvate (3C) produces: 4 ATP &amp; 2 NADHconsumes: 2 ATPnet: 2 ATP &amp; 2 NADHglucoseC-C-C-C-C-Cfructose-1,6bPP-C-C-C-C-C-C-PDHAPP-C-C-C G3PC-C-C-PpyruvateC-C-COverviewDHAP = dihydroxyacetone phosphateG3P = glyceraldehyde-3-phosphate</p></li><li><p>Pi364,5ADPNAD+GlucosehexokinasephosphoglucoseisomerasephosphofructokinaseGlyceraldehyde 3-phosphate (G3P)DihydroxyacetonephosphateGlucose 6-phosphateFructose 6-phosphateFructose 1,6-bisphosphateisomeraseglyceraldehyde3-phosphatedehydrogenasealdolase1,3-Bisphosphoglycerate(BPG)1,3-Bisphosphoglycerate(BPG)12ATPADPATPNADHNAD+NADHPiCH2COCH2OHPOCH2OPOCHOHCCH2OPOCHOHCH2OPOCH2OP OPOCH2HCH2OHOCH2POOCH2OHPO1st half of glycolysis (5 reactions)Glucose primingget glucose ready to splitphosphorylate glucose molecular rearrangementsplit destabilized glucose</p></li><li><p>2nd half of glycolysis (5 reactions)Payola! Finally some ATP!</p><p>NADH productionG3P donates Hoxidize sugarreduce NAD+NAD+ NADHATP productionG3P pyruvatePEP sugar donates PADP ATP78H2O910ADPATP3-Phosphoglycerate(3PG)3-Phosphoglycerate(3PG)2-Phosphoglycerate(2PG)2-Phosphoglycerate(2PG)Phosphoenolpyruvate(PEP)Phosphoenolpyruvate(PEP)PyruvatePyruvatephosphoglyceratekinasephosphoglyceromutaseenolasepyruvate kinaseADPATPADPATPADPATPH2OCH2OHCH3CH2O-OCPHCHOHO-O-O-CCCCCCPPOOOOOOCH2NAD+NADHNAD+NADHEnergy Harvest G3PC-C-C-PPiPi6</p></li><li><p>Substrate-level PhosphorylationP is transferred from PEP to ADPkinase enzymeADP ATPI get it!The PO4 came directly from the substrate!In the last steps of glycolysis, where did the P come from to make ATP?the sugar substrate (PEP)ATP</p></li><li><p>Substrate-Level PhosphorylationATP is formed when an enzyme transfers a phosphate group from a substrate to ADP.Example:PEP to PYR</p></li><li><p>Energy accounting of glycolysis Net gain = 2 ATPsome energy investment (-2 ATP)small energy return (+4 ATP)1 6C sugar 2 3C sugarsglucose pyruvate2x6C3CAll that work! And thats all I get?</p></li><li><p>Is that all there is?Not a lot of energyfor 1 billon years+ this is how life on Earth survivedno O2= slow growth, slow reproductiononly harvest 3.5% of energy stored in glucosemore carbons to strip off = more energy to harvestHard way to make a living! glucose pyruvate6C</p></li><li><p>GlycolysisSplits a glucosemolecule into 2 - 3 Carbon molecules calledPYRUVATE.products: 2 ATP, NADH and pyruvate</p></li><li><p>Glycolysis</p><p>glucose + 2ADP + 2Pi + 2 NAD+ 2 pyruvate + 2ATP + 2NADHWe cant stop there!Going to run out of NAD+without regenerating NAD+, energy production would stop!another molecule must accept H from NADH</p></li><li><p>NADHpyruvateacetyl-CoAlactateethanolNAD+NAD+NADHNAD+NADHCO2acetaldehydeH2OKrebscycleO2(lactic acid)with oxygenaerobic respirationwithout oxygenanaerobic respirationfermentationHow is NADH recycled to NAD+?Another molecule must accept H from NADHwhich path you use depends on who you are</p></li><li><p>Fermentation (anaerobic)Bacteria, yeastAnimals, some fungibeer, wine, breadcheese, anaerobic exercise (no O2)to glycolysisto glycolysis</p></li><li><p>Alcohol FermentationCount the carbons! Dead end processat ~12% ethanol, kills yeastcant reverse the reactionbacteria yeast</p></li><li><p>Reversible processonce O2 is available, lactate is converted back to pyruvate by the liverLactic Acid FermentationCount the carbons! animals</p></li><li><p>Pyruvate is a branching pointPyruvatemitochondriaKrebs cycleaerobic respirationfermentationanaerobic respiration</p></li><li><p>Without OxygenNo O2Alcoholic FermentationLactic Acid Fermentation</p></li><li><p>Whats the point?The point is to make ATP!ATP</p></li><li><p>And how do we do that?ATPBut Have we done that yet?ADPATP synthaseset up a H+ gradientallow H+ to flow through ATP synthasepowers bonding of Pi to ADP</p><p> ADP + Pi ATP</p></li><li><p>NO! Theres still more to my story!Any Questions?</p></li><li><p>Metabolism in the mitochondrial matrixOooooh! Form fits function!</p></li><li><p>Oxidation of pyruvate3C2C1CPyruvate enters mitochondria</p><p>3 step oxidation processreleases 1 CO2 (count the carbons!)reduces 2 NAD 2 NADH (moves e-)produces acetyl CoAAcetyl CoA enters Krebs cycleWhere does the CO2 go?Exhale!</p></li><li><p>Pyruvate oxidized to Acetyl CoA Yield = 2C sugar + NADH + CO2reductionoxidationCoenzyme APyruvateAcetyl CoAC-C-CC-CCO2</p></li><li><p>Krebs cycleaka Citric Acid Cyclein mitochondrial matrix8 step pathwayeach catalyzed by specific enzymestep-wise catabolism of 6C citrate moleculeEvolved later than glycolysisdoes that make evolutionary sense?bacteria 3.5 billion years ago (glycolysis)free O2 2.7 billion years ago (photosynthesis)eukaryotes 1.5 billion years ago (aerobic respiration = organelles mitochondria)1937 | 1953Hans Krebs1900-1981</p></li><li><p>citrateacetyl CoACount the carbons!pyruvatex 2oxidation of sugarsThis happens twice for each glucose molecule</p></li><li><p>citrateacetyl CoACount the electron carriers!pyruvatereduction of electron carriersThis happens twice for each glucose moleculex2</p></li><li><p>So we fully oxidized glucose C6H12O6CO2&amp; ended up with 4 ATP!Whassup?Whats the point? </p></li><li><p>Krebs cycle produces large quantities of electron carriersNADHFADH2go to Electron Transport ChainElectron Carriers = Hydrogen CarriersWhats so important about electron carriers? ATPADP + Pi</p></li><li><p>Energy accounting of Krebs cycle Net gain=2 ATP =8 NADH + 2 FADH2ATPpyruvate CO23C</p></li><li><p>Value of Krebs cycle?If the yield is only 2 ATP then how was the Krebs cycle an adaptation?value of NADH &amp; FADH2electron carriers &amp; H carriersreduced molecules move electronsreduced molecules move H+ ionsto be used in the Electron Transport Chainlike $$ in the bank</p></li><li><p>ATP accounting so farGlycolysis 2 ATP Krebs cycle 2 ATP Life takes a lot of energy to run, need to extract more energy than 4 ATP!Whats the point? A working muscle recycles over 10 million ATPs per secondTheres got to be a better way!</p></li><li><p>There is a better way!Electron Transport Chain series of molecules built into inner mitochondrial membranealong cristaetransport proteins &amp; enzymes transport of electrons down ETC linked to pumping of H+ to create H+ gradientyields ~34 ATP from 1 glucose!only in presence of O2 (aerobic respiration)That sounds more like it! </p></li><li><p>Electron Transport ChainIntermembrane spaceMitochondrial matrixQCNADH dehydrogenasecytochrome bc complexcytochrome c oxidase complex</p></li><li><p>G3PGlycolysisKrebs cycle8 NADH2 FADH2Remember the Electron Carriers? 4 NADHTime to break open the bank!glucose</p></li><li><p>Electron Transport Chainintermembrane spacemitochondrial matrixinner mitochondrial membraneNAD+QCNADH H2OH+e 2H+ + O2 H+H+eFADH2NADH dehydrogenasecytochrome bc complexcytochrome c oxidase complexFADeHH e- + H+NADH NAD+ + HHBuilding proton gradient!What powers the proton (H+) pumps?</p></li><li><p>ATPStripping H from Electron CarriersNADH passes electrons to ETCH cleaved off NADH &amp; FADH2electrons stripped from H atoms H+ (protons)electrons passed from one electron carrier to next in mitochondrial membrane (ETC)transport proteins in membrane pump H+ (protons) across inner membrane to intermembrane spaceADP + PiTA-DA!!Moving electrons do the work!</p></li><li><p>But what pulls the electrons down the ETC?electrons flow downhill to O2oxidative phosphorylation</p></li><li><p>Electrons flow downhillElectrons move in steps from carrier to carrier downhill to O2each carrier more electronegativecontrolled oxidationcontrolled release of energymake ATP instead of fire!</p></li><li><p>We did it!ATPSet up a H+ gradientAllow the protons to flow through ATP synthaseSynthesizes ATP</p><p>ADP + Pi ATPAre we there yet?proton-motive force</p></li><li><p>Structure of ATP synthaseHead section:it contain two parts, one is coupling factor1,it can synthesize ATP.the other is F1 inhibitory protein,it can prevent synthesization of ATP Stalk section:it can regulate the passage of protons.basal section:it can allows passage of proton, it allow proton to pass.</p></li><li><p>The diffusion of ions across a membranebuild up of proton gradient just so H+ could flow through ATP synthase enzyme to build ATPChemiosmosisChemiosmosis links the Electron Transport Chain to ATP synthesisSo thats the point!</p></li><li><p>Peter MitchellProposed chemiosmotic hypothesisrevolutionary idea at the time1961 | 19781920-1992proton motive force</p></li><li><p>taaaddaaa</p></li><li><p>ATP Synthase</p></li><li><p>Cellular respiration2 ATP~2 ATP2 ATP~34 ATP+++</p></li><li><p>GLYCOLYSISKREBSCYCLEInsert 1 Glucose2 energytokens(ATP)2 energytokens32 energytokensELECTRONTRANSPORT CHAIN--------reactantsproductsGLYCOLYSISglucoseOxygenWater2 ATP2 NADH2 NADH6 NADH2 FADH22 ATP32 ATPKREBSCYCLEELECTRONTRANSPORTCHAINglucose derivativescarbon dioxidecarbon dioxidecytosolmitochondrion</p></li><li><p>Summary of cellular respirationWhere did the glucose come from?Where did the O2 come from?Where did the CO2 come from?Where did the CO2 go?Where did the H2O come from?Where did the ATP come from?What else is produced that is not listed in this equation?Why do we breathe?</p></li><li><p>ETC backs upnothing to pull electrons down chainNADH &amp; FADH2 cant unload HATP production ceasescells run out of energyand you die!Taking it beyondWhat is the final electron acceptor in Electron Transport Chain?O2So what happens if O2 unavailable?</p></li><li><p>You cannot live on sugar [glucose] alone!--your MomProteinsBreak into AAsDeaminateAlanine to pyruvateGlutamate to ketoglutarateAspartate to oxaloacetateAAs join the Krebs cycle at different pointsFATSDegrade into individual fatty acids &amp; glycerolOxidized in matrixenzymes attack long fatty acid chains and remove 2C chunksEntire chain is converted into acetyl-CoACalled Beta oxidationGlycerol is converted into pyruvate.</p></li><li><p>BIOSYNTHESISWhen there is an excess of intermediates they can be used to build necessary molecules. Lipids can be generated from excess acetyl CoAGlycogen is generated from excess pyruvateAmino acids are genertated from different stages of the krebs cycle. </p></li><li><p>***Why does it make sense that this happens in the cytosol?Who evolved first?**1st ATP used is like a match to light a fire initiation energy / activation energy.</p><p>Destabilizes glucose enough to split it in two***And thats how life subsisted for a billion years.Until a certain bacteria learned how to metabolize O2; which was previously a poison.But now pyruvate is not the end of the processPyruvate still has a lot of energy in it that has not been captured.It still has 3 carbons bonded together! There is still energy stored in those bonds. It can still be oxidized further. *So why does glycolysis still take place?**Count the carbons!!</p><p>Lactic acid is not a dead end like ethanol. Once you have O2 again, lactate is converted back to pyruvate by the liver and fed to the Krebs cycle.******CO2 is fully oxidized carbon == cant get any more energy out itCH4 is a fully reduced carbon == good fuel!!!*Release CO2 because completely oxidizedalready released all energy it can release no longer valuable to cell.</p><p>Because whats the point?The Point is to make ATP!!!**A 2 carbon sugar went into the Krebs cycle and was taken apart completely. Two CO2 molecules were produced from that 2 carbon sugar. Glucose has now been fully oxidized!</p><p>But wheres all the ATP??? *Everytime the carbons are oxidized, an NAD+ is being reduced.</p><p>But waitwheres all the ATP??**********Oxidation refers to the loss of electrons to any electron acceptor, not just to oxygen. Uses exergonic flow of electrons through ETC to pump H+ across membrane.*Pumping H+ across membrane what is energy to fuel that?Cant be ATP! that would cost you what you want to make! Its like cutting off your leg to buy a new pair of shoes. :-(Flow of electrons powers pumping of H+</p><p>O2 is 2 oxygen atoms both looking for electrons*Electrons move from molecule to molecule until they combine with O &amp; H ions to form H2O</p><p>Its like pumping water behind a dam -- if released, it can do work </p><p>**Chemiosmosis is the diffusion of ions across a membrane. More specifically, it relates to the generation of ATP by the movement of hydrogen ions across a membrane.</p><p>Hydrogen ions (protons) will diffuse from an area of high proton concentration to an area of lower proton concentration. Peter Mitchell proposed that an electrochemical concentration gradient of protons across a membrane could be harnessed to make ATP. He likened this process to osmosis, the diffusion of water across a membrane, which is why it is called chemiosmosis.****Where did the glucose come from?from food eatenWhere did the O2 come from?breathed inWhere did the CO2 come from?oxidized carbons cleaved off of the sugarsWhere did the CO2 go?exhaledWhere did the H2O come from?from O2 after it accepts electrons in ETCWhere did the ATP come from?mostly from ETCWhat else is produced that is not listed in this equation?NAD, FAD, heat!*What if you have a chemical that punches holes in the inner mitochondrial membrane?</p></li></ul>


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