Making energy! The energy needs of life rganisms are endergonic systems What do we need energy for? synthesis building biomolecules reproduction movement active transport temperature regulation The point is to make! 008-009 Where do we get the energy from? Work of life is done by energy coupling use exergonic (catabolic) reactions to fuel endergonic (anabolic) reactions digestion synthesis + + energy + + energy Living economy Fueling the body s economy eat high energy organic molecules food = carbohydrates, lipids, proteins, nucleic acids break them down digest = catabolism capture released energy in a form the cell can use Need an energy currency a way to pass energy around need a short term energy storage molecule Whoa! ot stuff! Adenosine Trihosphate modified nucleotide nucleotide = adenine + ribose + i AM AM + i + i adding phosphates is endergonic ow efficient! Build once, use many ways high energy bonds ow does store energy? AM I think he s a bit unstable don t you? Each negative 4 more difficult to add a lot of stored energy in each bond most energy stored in 3rd i 3rd i is hardest group to keep bonded to molecule Bonding of negative i groups is unstable spring-loaded i groups pop off easily & release energy Instability of its bonds makes an excellent energy donor 1
ow does transfer energy? releases energy G = -7.3 kcal/mole Fuel other reactions hosphorylation released i can transfer to other molecules destabilizing the other molecules that phosphorylates = kinase + 7.3 energy An example of hosphorylation Building polymers from monomers need to destabilize the monomers phosphorylate! synthesis + + +4. kcal/mol kinase It s + + never that -7.3 kcal/mol simple! + -3.1 kcal/mol + i Another example of hosphorylation The first steps of cellular respiration beginning the breakdown of to make Those phosphates sure make it uncomfortable hexokinase around here! phosphofructokinase ----- fructose-1,6b ------- DA --- G3 --- activation energy / cycle an t store good energy donor, not good energy storage too reactive transfers i too easily only short term energy storage carbohydrates & fats are long term energy storage Whoa! ass me the (and )! cellular respiration + i 7.3 kcal/mole A working muscle recycles over 10 million s per second ells spend a lot of time making! The point is to make! What s the point? synthase Enzyme channel in mitochondrial membrane permeable to flow down concentration gradient flow like water over water wheel flowing + cause change in shape of synthase powers bonding of i to : + i + But ow is the proton ( ) gradient formed? rotor rod catalytic head
respiration That s the rest of my story! Any Questions? ellular Respiration arvesting hemical Energy 008-009 006-007 What s the point? The point is to make! arvesting stored energy Energy is stored in organic molecules carbohydrates, fats, proteins eterotrophs eat these organic molecules food digest organic molecules to get raw materials for synthesis fuels for energy controlled release of energy burning fuels in a series of step-by-step -controlled reactions 006-007 arvesting stored energy Glucose is the model catabolism of to produce + oxygen energy + water + carbon dioxide 6 1 6 + 6 + 6 + 6 + heat ow do we harvest energy from fuels? Digest large molecules into smaller ones break bonds & move electrons from one molecule to another as electrons move they carry energy with them that energy is stored in another bond, released as heat or harvested to make MBUSTIN = making a lot of heat energy by burning fuels in one step fuel carbohydrates) + + heat RESIRATIN = making (& some heat) by burning fuels in many small steps s + + (+ heat) loses e- gains e- oxidized reduced + + + e - e - redox e - reduction 3
ow do we move electrons in biology? Moving electrons in living systems electrons cannot move alone in cells electrons move as part of atom move = move electrons e p loses e- gains e- oxidized reduced + + + reduction 6 1 6 + 6 6 + 6 + e - reduction oupling & reduction REDX reactions in respiration release energy as breakdown organic molecules break - bonds strip off electrons from - bonds by removing atoms 6 1 6 = the fuel has been oxidized electrons attracted to more electronegative atoms in biology, the most electronegative atom? = oxygen has been reduced couple REDX reactions & use the released energy to synthesize 6 1 6 + 6 6 + 6 + reduction xidation & reduction xidation Reduction adding removing loss of electrons releases energy exergonic removing adding gain of electrons stores energy endergonic 6 1 6 + 6 6 + 6 + reduction Moving electrons in respiration Electron carriers move electrons by shuttling atoms around nicotinamide Vitamin B3 niacin phosphates (reduced) FAD + FAD (reduced) N + adenine ribose sugar N + reduction carries electrons as a reduced molecule like $$ in the bank reducing power! N N + ow efficient! Build once, use many ways verview of cellular respiration 4 metabolic stages Anaerobic respiration 1. Glycolysis respiration without in cytosol Aerobic respiration respiration using in mitochondria. yruvate 3. Krebs cycle 4. Electron transport chain What s the point? The point is to make! 6 1 6 + 6 + 6 + 6 (+ heat) 006-007 4
And how do we do that? synthase flows through it conformational changes bond i to to make set up a gradient allow the to flow down concentration gradient through synthase + i + But ow is the proton ( ) gradient formed? ellular Respiration Stage 1: Glycolysis 007-008 What s the point? The point is to make! 007-008 Glycolysis Breaking down glyco lysis (splitting sugar) pyruvate 6 x 3 ancient pathway which harvests energy where energy transfer first evolved transfer energy from organic molecules to still is starting point for ALL cellular respiration but it s inefficient generate only for every 1 occurs in cytosol That s not enough for me! In the cytosol? Why does that make evolutionary sense? Evolutionary perspective rokaryotes first cells had no organelles Anaerobic atmosphere life on Earth first evolved without free oxygen ( ) in atmosphere energy had to be captured from organic molecules in absence of rokaryotes that evolved glycolysis are ancestors of all modern life ALL cells still utilize glycolysis Enzymes of glycolysis are well-conserved You mean we re related? Do I have to invite them over for the holidays? verview 10 reactions convert (6) to pyruvate (3) produces: 4 & consumes: net yield: & DA = dihydroxyacetone phosphate G3 = glyceraldehyde-3-phosphate ----- fructose-1,6b ------- DA --- G3 --- i i pyruvate -- 4 4 5
Glycolysis summary ENERGY INVESTMENT ENERGY AYFF NET YIELD G3 --- - 4 endergonic invest some exergonic harvest a little & a little like $$ in the bank net yield 1st half of glycolysis (5 reactions) Glucose priming get ready to split phosphorylate molecular rearrangement split destabilized Glucose 1 hexokinase Glucose 6-phosphate phospho isomerase Fructose 6-phosphate 3 phosphofructokinase Fructose 1,6-bisphosphate 4,5 aldolase isomerase Dihydroxyacetone phosphate Glyceraldehyde 3 -phosphate (G3) 6 i i glyceraldehyde 3-phosphate dehydrogenase 1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate (BG) (BG) nd half of glycolysis (5 reactions) Energy arvest production G3 donates oxidizes the sugar reduces production G3 pyruvate E sugar donates substrate level phosphorylation ayola! Finally some! 3-hosphoglycerate (3G) -hosphoglycerate (G) 7 phosphoglycerate kinase 8 phosphoglyceromutase 9 enolase hosphoenolpyruvate (E) DA --- yruvate i 6 10 pyruvate kinase G3 --- i 3-hosphoglycerate (3G) -hosphoglycerate (G) hosphoenolpyruvate (E) yruvate - - - - 3 Substrate-level hosphorylation In the last steps of glycolysis, where did the come from to make? the sugar substrate (E) is transferred from E to kinase I get it! The i came directly from the substrate! 9 enolase hosphoenolpyruvate (E) yruvate 10 pyruvate kinase hosphoenolpyruvate (E) yruvate - - 3 Energy accounting of glycolysis pyruvate 6 x 3 4 4 But has Net gain = + some energy investment (- ) small energy return (4 + ) 1 6 sugar 3 sugars so much more to give! All that work! And that s all I get? Is that all there is? Not a lot of energy for 1 billon years + this is how life on Earth survived no = slow growth, slow reproduction only harvest 3.5% of energy stored in more carbons to strip off = more energy to harvest pyruvate 6 x 3 ard way to make a living! 6
But can t stop there! raw materials products Glycolysis NAD so is freed up for another round 3-hosphoglycerate (3G) -hosphoglycerate (G) hosphoenolpyruvate (E) yruvate i 6 7 8 9 10 i 3-hosphoglycerate (3G) + + i + pyruvate + + Going to run out of without regenerating, energy production would stop! another molecule must accept from DA 1,3-BG i i G3 1,3-BG -hosphoglycerate (G) hosphoenolpyruvate (E) yruvate NAD ow is recycled to? Another molecule must accept from recycle who you are which path you use depends on with oxygen aerobic respiration pyruvate acetyl-oa Krebs cycle lactate lactic acid fermentation without oxygen anaerobic respiration fermentation acetaldehyde ethanol alcohol fermentation Fermentation (anaerobic) Bacteria, yeast pyruvate ethanol + 3 1 beer, wine, bread back to glycolysis Animals, some fungi pyruvate lactic acid 3 3 back to glycolysis cheese, anaerobic exercise (no ) Alcohol Fermentation pyruvate ethanol + 3 1 back to glycolysis Dead end process at ~1% ethanol, kills yeast can t reverse the reaction ount the carbons! bacteria yeast recycle Lactic Acid Fermentation pyruvate lactic acid 3 3 Reversible process once is available, lactate is converted back to pyruvate by the liver back to glycolysis ount the carbons! animals some fungi recycle yruvate is a branching point yruvate fermentation anaerobic respiration mitochondria Krebs cycle aerobic respiration 7
What s the point? The point is to make! And how do we do that? synthase set up a gradient allow to flow through synthase powers bonding of i to + i + But ave we done that yet? verview 10 reactions convert (6) to pyruvate (3) produces: 4 & consumes: net: & ----- fructose-1,6b ------- DA --- G3 --- i i pyruvate -- 4 4 ellular Respiration Stage & 3: xidation of yruvate Krebs ycle 006-007 Glycolysis is only the start Glycolysis pyruvate 6 x 3 yruvate has more energy to yield 3 more to strip off (to oxidize) if is available, pyruvate enters mitochondria s of Krebs cycle complete the full of sugar to ellular respiration pyruvate 3 1 8
Mitochondria Structure Double membrane energy harvesting organelle smooth outer membrane highly folded inner membrane cristae intermembrane space fluid-filled space between membranes matrix inner fluid-filled space DNA, ribosomes s outer intermembrane space inner membrane free in matrix & membrane-bound membrane cristae matrix What cells would have A a lot Biology of mitochondria? mitochondrial DNA Mitochondria Function Dividing mitochondria Who else divides like that? bacteria! What does this tell us about the evolution of eukaryotes? Endosymbiosis! ooooh! Form fits function! Membrane-bound proteins Enzymes & permeases Advantage of highly folded inner membrane? More surface area for membranebound s & permeases xidation of pyruvate yruvate enters mitochondrial matrix x pyruvate acetyl oa + [ 3 1 ] NAD 3 step process releases (count the carbons!) reduces NAD (moves e - ) produces acetyl oa Acetyl oa enters Krebs cycle Where does the go? Exhale! yruvate oxidized to Acetyl oa yruvate -- reduction o A Acetyl oa - x [ Yield = sugar + NAD ] Krebs cycle aka itric Acid ycle in mitochondrial matrix 1937 1953 8 step pathway ans Krebs each catalyzed by specific 1900-1981 step-wise catabolism of 6 citrate molecule Evolved later than glycolysis does that make evolutionary sense? bacteria 3.5 billion years ago (glycolysis) free.7 billion years ago (photosynthesis) eukaryotes 1.5 billion years ago (aerobic respiration = organelles mitochondria) ount the carbons! pyruvate 3 This happens twice for each molecule 4 4 4 4 of sugars x acetyl oa 6 4 citrate 6 5 9
ount the electron carriers! pyruvate 3 This happens twice for each molecule 4 4 4 acetyl oa 6 reduction of electron carriers x citrate 6 5 Whassup? So we fully oxidized 6 1 6 & ended up with 4! FAD 4 4 What s the point? Electron arriers = ydrogen arriers + Krebs cycle + + produces large quantities of electron carriers + i FAD go to Electron Transport hain! What s so important about electron carriers? x Energy accounting of Krebs cycle 4 1 FAD 4 NAD 1 FAD pyruvate 3 3x 1 1 1 Net gain = = 8 NAD FAD Value of Krebs cycle? If the yield is only then how was the Krebs cycle an adaptation? What s the point? value of & FAD electron carriers & carriers reduced molecules move electrons reduced molecules move ions to be used in the Electron Transport hain like $$ in the bank The point is to make! 10
And how do we do that? synthase set up a gradient allow to flow through synthase powers bonding of i to + ellular Respiration Stage 4: Electron Transport hain + i But ave we done that yet? 006-007 ellular respiration What s the point? The point is to make! 006-007 accounting so far Glycolysis Kreb s cycle Life takes a lot of energy to run, need to extract more energy than 4! There s got to be a better way! I need a lot more! A working muscle recycles over 10 million s per second There is a better way! Electron Transport hain series of proteins built into inner mitochondrial membrane along cristae transport proteins & s transport of electrons down ET linked to pumping of to create gradient yields ~36 from 1! only in presence of (aerobic respiration) That sounds more like it! 11
Mitochondria Double membrane outer membrane inner membrane highly folded cristae s & transport proteins intermembrane space fluid-filled space between membranes ooooh! Form fits function! Electron Transport hain Intermembrane space Q dehydrogenase Mitochondrial matrix cytochrome bc complex Inner mitochondrial membrane cytochrome c oxidase complex Remember the Electron arriers? Glycolysis Time to break open the piggybank! G3 Krebs cycle 8 FAD Electron Transport hain + e- + e p Building proton gradient! intermembrane space inner mitochondrial membrane Q e e e FAD FAD 1 + cytochrome cytochrome c dehydrogenase bc complex oxidase complex mitochondrial matrix What powers the proton ( ) pumps? Stripping from Electron arriers Electron carriers pass electrons & to ET cleaved off & FAD electrons stripped from atoms (protons) electrons passed from one electron carrier to next in mitochondrial membrane (ET) flowing electrons = energy to do work transport proteins in membrane pump (protons) across inner membrane to intermembrane space TA-DA!! + Moving electrons do the work! Q e e e FAD FAD 1 + + i cytochrome cytochrome c dehydrogenase bc complex oxidase complex But what pulls the electrons down the ET? electrons flow downhill to oxidative phosphorylation 1
Electrons flow downhill Electrons move in steps from carrier to carrier downhill to oxygen each carrier more electronegative controlled controlled release of energy make instead of fire! We did it! Set up a gradient Allow the protons to flow through synthase Synthesizes + i + i proton-motive force Are we there yet? hemiosmosis The diffusion of ions across a membrane build up of proton gradient just so + could flow through synthase to build 1961 1978 eter Mitchell roposed chemiosmotic hypothesis revolutionary idea at the time hemiosmosis links the Electron Transport hain to synthesis proton motive force So that s the point! 190-199 yruvate from cytoplasm Inner mitochondrial membrane Q Intermembrane space Electron transport system ellular respiration 1. Electrons are harvested Acetyl-oA and carried to the transport system. e - Krebs cycle e - FAD e - 3. xygen joins with protons to form water.. Electrons provide energy to pump protons across the membrane. 1 + e - Mitochondrial matrix 4. rotons diffuse back in down their concentration gradient, driving the synthesis of. synthase + + ~34 13
Summary of cellular respiration Where did the come from? Where did the come from? Where did the come from? Where did the go? Where did the come from? Where did the come from? What else is produced that is not listed in this equation? Why do we breathe? 6 1 6 + 6 6 + 6 + ~38 Taking it beyond + What is the final electron acceptor in Q e Electron Transport hain? e FAD NAD + cytochrome dehydrogenase bc complex So what happens if unavailable? ET backs up nothing to pull electrons down chain & FAD can t unload production ceases cells run out of energy and you die! FAD e 1 + cytochrome c oxidase complex ellular respiration ellular Respiration ther Metabolites & ontrol of Respiration Beyond : ther carbohydrates Glycolysis accepts a wide range of carbohydrates fuels polysaccharides hydrolysis ex. starch, glycogen other 6 sugars modified ex. galactose, fructose Beyond : roteins proteins amino acids hydrolysis waste amino group = waste product excreted as ammonia, urea, or uric acid N R glycolysis Krebs cycle sugar = carbon skeleton = enters glycolysis or Krebs cycle at different stages 14
Beyond : Fats fats glycerol + fatty acids hydrolysis glycerol (3) G3 glycolysis fatty acids acetyl acetyl Krebs groups coa cycle arbohydrates vs. Fats Fat generates x vs. carbohydrate more in gram of fat more energy releasing bonds more in gram of carbohydrate so it s already partly oxidized less energy to release That s why it takes so much to lose a pound a fat! fat 3 glycerol fatty acids carbohydrate enters glycolysis A as Biology G3 enter Krebs cycle as acetyl oa Metabolism oordination of chemical processes across whole organism digestion catabolism when organism needs energy or needs raw materials synthesis anabolism when organism has enough energy & a supply of raw materials by regulating s feedback mechanisms raw materials stimulate production products inhibit further production Metabolism Digestion digestion of carbohydrates, fats & proteins all catabolized through same pathways enter at different points cell extracts energy from every source ells are versatile & selfish! Metabolism Synthesis enough energy? build stuff! cell uses points in glycolysis & Krebs cycle as links to pathways for synthesis run pathways backwards have extra fuel, build fat! pyruvate ells are versatile & thrifty! arbohydrate Metabolism The many stops on the arbohydrate Line from Krebs cycle back through glycolysis Krebs cycle intermediaries amino acids gluconeogenesis acetyl oa fatty acids 15
Lipid Metabolism The many stops on the Lipid Line from Krebs cycle (acetyl oa) to a variety of lipid synthesis pathways Amino Acid Metabolism The many stops on the Amino Acid Line from Krebs cycle & glycolysis to an array of amino acid synthesis pathways 8 essential amino acids 1 synthesized aa s Nucleotide Metabolism The many stops on the GAT Line sugar from glycolysis phosphate & N-base from Krebs cycle entral Role of Acetyl oa Acetyl oa is central to both energy production & biomolecule synthesis Depending on yruvate rotein organism s need build co A immediate use build fat stored energy Fat Glycolysis Acetyl coa Lipid Glucose Glycolysis yruvate Krebs cycle ET acetyl group ontrol of Respiration Feedback ontrol Feedback Inhibition Regulation & coordination of production final product is inhibitor of earlier step allosteric inhibitor of earlier no unnecessary accumulation of product production is self-limiting A B D E F G X 1 3 4 5 6 006-007 allosteric inhibitor of 1 16
Respond to cell s needs Key point of control phosphofructokinase allosteric regulation of why here? can t turn back step before splitting AM & stimulate inhibits citrate inhibits Why is this regulation important? Balancing act: availability of raw materials vs. A energy Biology demands vs. synthesis A Metabolic economy Basic principles of supply & demand regulate metabolic economy balance the supply of raw materials with the products produced these molecules become feedback regulators they control s at strategic points in glycolysis & Krebs cycle levels of AM,, regulation by final products & raw materials levels of intermediates compounds in pathways regulation of earlier steps in pathways levels of other biomolecules in body regulates rate of siphoning off to synthesis pathways It s a Balancing Act yruvate Balancing synthesis with availability of both energy & raw materials is essential for survival! rotein do it well & you survive longer you survive longer & you have more offspring you have more offspring & you get to take over the world Fat Glycolysis Lipid Glucose Glycolysis yruvate Krebs cycle ET 17