hapter 07 ellular Respiration 1 http://www.mobento.com/video/diyoea5mc
**Important study hints** Draw out processes on paper and label structures and steps Keep working on those flash cards! http://getyournotes.blogspot.com/2012/01/cellular-respiration-aerobic-and.html 2
Respiration rganisms can be classified based on how they obtain energy: Autotrophs Able to produce their own organic molecules through photosynthesis eterotrophs Live on organic compounds produced by other organisms All organisms use cellular respiration to extract energy from organic molecules 3 http://en.wikipedia.org/wiki/eterotroph
http://chemwiki.ucdavis.edu/analytical_hemistry/electrochemistry/redox_hemistry/xidizing_and_reducing_agents ellular respiration ellular respiration is a series of reactions xidation loss of electrons Reduction gain of electron Dehydrogenation lost electrons are accompanied by protons A hydrogen atom is lost (1 electron, 1 proton) 4
http://chemwiki.ucdavis.edu/analytical_hemistry/electrochemistry/redox_hemistry/xidizing_and_reducing_agents Redox During redox reactions, electrons carry energy from one molecule to another Redox reactions are often coupled with an electron carrier (NAD + ) Reduced compound A (reducing agent) A e - e- xidized compound B (oxidizing agent) B A e - e- B A is oxidized B is reduced 5
Redox Nicotinamide adenosine dinucleotide (NAD +) An electron carrier NAD + accepts 2 electrons and 1 proton from another molecule to become NAD Reaction is reversible As energy-rich molecule is oxidized, NAD + is reduced to NAD Energy-rich molecule Enzyme NAD + NAD + xidation Reduction 2e + Product ++ NAD + NAD NAD 6
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Note change from textbook xidation Energy-rich molecule Reduction Product Enzyme + + 2e + NAD + NAD + NAD NAD NAD + 1. Enzymes that use NAD + as a cofactor for oxidation reactions bind NAD + and the substrate. 2. In an oxidation reduction reaction, 2 electrons and a proton are transferred to NAD +, forming NAD. A second proton is donated to the solution. 3. NAD diffuses away and can then donate electrons to other molecules. As energy-rich molecule is oxidized, NAD + is reduced to NAD 7
In overall cellular energy harvest Dozens of redox reactions take place Number of electron acceptors, including NAD + In the end, high-energy electrons from initial chemical bonds have lost much of their energy Electrons are transferred to a final electron acceptor A NAD+ B xidation Reduction xidation Reduction A NAD B 8
Types of ellular Respiration Aerobic respiration Final electron receptor is oxygen ( 2 ) Anaerobic respiration Final electron acceptor is an inorganic molecule (not 2 ) Fermentation Final electron acceptor is an organic molecule, such as lactic acid or ethanol 9
Aerobic respiration 6 12 6 + 6 2 6 2 + 6 2 Free energy = 686 kcal/mol of glucose Free energy can be even higher than this in a cell This large amount of energy must be released in small steps rather than all at once. 6 12 6 (general form for 6 carbon sugar such as glucose) 10
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Electrons from food 2e Energy released for synthesis igh energy Low energy 2 + 1 / 2 2 2 11
Electron carriers Many types of carriers used Soluble, membrane-bound, move within membrane All carriers can be easily oxidized and reduced Some carry just electrons, some electrons and protons NAD + acquires 2 electrons and a proton to become NAD 12
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Reduction N 2 + 2 xidation N 2 + + P 2 N P 2 N P N N 2 N P N N 2 N 2 N N Adenine 2 N N Adenine NAD + : xidized form of nicotinamide NAD: Reduced form of nicotinamide 13
ells use to drive endergonic reactions ΔG (free energy) = 7.3 kcal/mol ompare with ΔG from complete combustion of glucose = 686 kcal/mol ellular reactions can t use all the energy of glucose breakdown at once, so cells must use stepwise breakdown and intermediaries such as http://fgamedia.org/faculty/cholcroft/bio45/miscellaneous_web_pages/lectures/metabolism/metabolism_intro.html 14
2 mechanisms for synthesis 1. Substrate-level phosphorylation Transfer phosphate group directly from substrate molecule to ADP During glycolysis and Krebs cycle PEP Enzyme P P P Adenosine ADP Enzyme 2. xidative phosphorylation synthase uses energy from a proton gradient in the electron transport chain 15
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. PEP P Enzyme P Enzyme P Adenosine ADP 16
xidation of Glucose The complete oxidation of glucose proceeds in stages: 1. Glycolysis 2. Pyruvate oxidation 3. Krebs cycle 4. Electron transport chain & chemiosmosis 17 http://www.mobento.com/video/diyoea5mc
NAD opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. uter Glycolysis mitochondrial membrane Glucose Intermembrane space Pyruvate Pyruvate xidation Mitochondrial matrix NAD Acetyl-oA 2 NAD 2 Krebs ycle FAD 2 e NAD + FAD 2 2 Inner mitochondrial membrane e e Electron Transport hain hemiosmosis Synthase + 18
Glycolysis onverts 1 glucose (6 carbons) to 2 pyruvate (3 carbons) 10-step biochemical pathway ccurs in the cytoplasm 2 NAD produced by the reduction of NAD + Net production of 2 molecules by substrate-level phosphorylation (uses 2 s and produces 4 total = 2 net s) Fun fact nly process that occurs in red blood cells since they do not have mitochondria! 19
xidation and Formation leavage Priming Reactions opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Glycolysis NAD Pyruvate xidation Krebs ycle Electron Transport hain hemiosmosis 6-carbon glucose (Starting material) ADP ADP Glycolysis begins with the addition of energy. Two highenergy phosphates (P) from two molecules of are added to the 6-carbon molecule glucose, producing a 6-carbon molecule with two phosphates. P P 6-carbon sugar diphosphate Then, the 6-carbon molecule with two phosphates is split in two, forming two 3-carbon sugar phosphates. P P P i 3-carbon sugar phosphate NAD + NAD + NAD ADP ADP 3-carbon sugar phosphate P i NAD ADP ADP An additional Inorganic phosphate ( P i ) is incorporated into each 3-carbon sugar phosphate. An oxidation reaction converts the two sugar phosphates into intermediates that can transfer a phosphate to ADP to form. The oxidation reactions also yield NAD giving a net energy yield of 2 and 2 NAD. 3-carbon pyruvate 3-carbon pyruvate 20
Pyruvate Phosphoenolpyruvate 2-Phosphoglycerate 3-Phosphoglycerate 1,3-Bisphosphoglycerate Dihydroxyacetone Phosphate Glyceraldehyde 3-phosphate Fructose 1,6-bisphosphate Fructose 6-phosphate Glucose 6-phosphate Glucose opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. NAD Glycolysis Pyruvate xidation Krebs ycle Glycolysis: The Reactions Glucose 1 exokinase ADP Glucose 6-phosphate 2 2 P Electron Transport hain hemiosmosis 2 Phosphoglucose isomerase Fructose 6-phosphate 2 P 2 3 1. Phosphorylation of glucose by. 2 3. Rearrangement, followed by a second phosphorylation. Phosphofructokinase AD P Fructose 1,6-bisphosphate 4 5 Aldolase Isomerase P 2 2 P 4 5. The 6-carbon molecule is split into two 3-carbon moleculesone G3P, another that is converted into G3P in another reaction. Dihydroxyacetone phosphate NAD+ P i 6 Glyceraldehyde 3- phosphate (G3P) P i NAD+ P 2 2 2 P 6. xidation followed by phosphorylation produces two NAD molecules and two molecules of BPG, each with one high-energy phosphate bond. 7. Removal of high-energy phosphate by two ADP molecules produces two molecules and leaves two 3PG molecules. NAD 1,3-Bisphosphoglycerate (BPG) ADP 3-Phosphoglycerate (3PG) Glyceraldehyde 3-phosphate dehydrogenase 7 Phosphoglycerate kinase NAD 1,3-Bisphosphoglycerate (BPG) ADP 3-Phosphoglycerate (3PG) P 2 2 P P 8 9. Removal of water yields two PEP molecules, each with a high-energy phosphate bond. 10. Removal of high-energy phosphate by two ADP molecules produces two molecules and two pyruvate molecules. 2-Phosphoglycerate (2PG) 2 8 Phosphoglyceromutase 9 Enolase 2-Phosphoglycerate (2PG) 2 2 P Phosphoenolpyruvate Phosphoenolpyruvate (PEP) (PEP) 2 P ADP 10 Pyruvate kinase ADP 21 Pyruvate Pyruvate 3
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NAD must be recycled http://getyournotes.blogspot.com/2012/01/cellular-respiration-aerobic-and.html For glycolysis to continue, NAD must be recycled to NAD + by either: 1. Aerobic respiration xygen is available as the final electron acceptor Produces significantly more 2. Fermentation ccurs when oxygen is not available rganic molecule is the final electron acceptor 23
Fate of pyruvate Depends on oxygen availability When oxygen is present, pyruvate is oxidized to acetyl- oa which enters the Krebs cycle Aerobic respiration Without oxygen, pyruvate is reduced in order to oxidize NAD back to NAD + Fermentation 24 http://getyournotes.blogspot.com/2012/01/cellular-respiration-aerobic-and.html
Without oxygen, pyruvate is reduced by lactate or alcohol fermentation This oxidizes NAD back to NAD + Pyruvate Without oxygen 2 NAD + With oxygen 2 2 NAD NAD Acetaldehyde ET in mitochondria This is important because NAD + must be recycled so glycolysis can continue to operate Acetyl-oA Krebs ycle NAD + Lactate NAD NAD + Ethanol 25 opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display.
Pyruvate xidation In the presence of oxygen, pyruvate is oxidized ccurs in the mitochondria in eukaryotes multienzyme complex called pyruvate dehydrogenase catalyzes the reaction ccurs at the plasma membrane in prokaryotes http://schoolworkhelper.net/cellular-respiration-glycolysis-pyruvate-kerbs-etc/ 26
Products of pyruvate oxidation For each 3-carbon pyruvate molecule: 1 2 Decarboxylation by pyruvate dehydrogenase 1 NAD 1 Acetyl-oA which consists of 2 carbons from pyruvate attached to coenzyme A Acetyl-oA proceeds to the Krebs cycle ***Double each of these products per glucose molecule 27 http://schoolworkhelper.net/cellular-respiration-glycolysis-pyruvate-kerbs-etc/
Acetyl oenzyme A Pyruvate opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Glycolysis NAD Pyruvate xidation Krebs ycle Electron Transport hain hemiosmosis Pyruvate xidation: The Reaction Per glucose molecule = 2 2 2 NADs 2 Acetyl oa Pyruvate 2 NAD + NAD oa Acetyl oenzyme A 3 S oa 3 28
Krebs ycle xidizes the acetyl group from pyruvate ccurs in the matrix of the mitochondria Biochemical pathway of 9 steps in three segments 1. Acetyl-oA + oxaloacetate citrate 2. itrate rearrangement and decarboxylation 3. Regeneration of oxaloacetate 3 1 2 29 http://drchadedwards.com/244/energy-production-through-the-krebs-cycle/
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Glycolysis 1 Pyruvate xidation oa- (Acetyl-oA) oa NAD FAD 2 Krebs ycle Electron Transport hain hemiosmosis NAD 4-carbon molecule (oxaloacetate) 6-carbon molecule (citrate) NAD + 2 NAD + NAD 2 Pyruvate from glycolysis is oxidized Krebs ycle into an acetyl group that feeds into the Krebs cycle. The 2- acetyl group combines with 4- oxaloacetate to produce the 6- compound citrate (thus this is also called the citric acid cycle). xidation reactions are combined with two decarboxylations to produce NAD, 2, and a new 4-carbon molecule. Two additional oxidations generate another NAD and an FAD 2 and regenerate the original 4- oxaloacetate. FAD 2 4-carbon molecule FAD 4-carbon molecule Krebs ycle 4-carbon molecule 5-carbon molecule 2 NAD + NAD 3 ADP + P 30
Krebs ycle For each Acetyl-oA entering: Release 2 molecules of 2 Reduce 3 NAD + to 3 NAD Reduce 1 FAD (electron carrier) to FAD 2 Produce 1 Regenerate oxaloacetate 31 http://drchadedwards.com/244/energy-production-through-the-krebs-cycle/
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Glycolysis 1. Reaction 1: ondensation Pyruvate xidation 2 3. Reactions 2 and 3: Isomerization 4. Reaction 4: The first oxidation NAD F AD 2 Krebs ycle 5. Reaction 5: The second oxidation 6. Reaction 6: Substrate-level phosphorylation Electron T ransport hain hemiosmosis 7. Reaction 7: The third oxidation 8 9. Reactions 8 and 9: Regeneration of oxaloacetate and the fourth oxidation Krebs ycle: The Reactions Acetyl-oA Per glucose molecule, the Krebs cycle produces 4 2 6 NADs 2 FAD 2 2 FAD 2 FAD 2 7 8 Fumarate (4) Succinate (4) 2 2 Malate (4) 2 Fumarase NAD + Succinate dehydrogenase oa-s 9 NAD Malate dehydrogenase Succinyl-oA synthetase xaloacetate (4) 2 Succinyl-oA (4) 3 S 1 oa oa-s itrate synthetase 2 itrate (6) Isocitrate dehydrogenase 2 2 2 2 Aconitase 3 Isocitrate (6) 2 4 NAD + -Ketoglutarate (5) 2 NAD ADP GTP 6 GDP + P i 2 2 S oa -Ketoglutarate dehydrogenase 5 oa-s NAD NAD + 2 32
At this point Glucose has been oxidized to: 6 2 (byproduct of aerobic respiration) 4 10 NAD These two types of electron carriers proceed to the electron transport chain 2 FAD 2 Electron transfer has released 53 kcal/mol of energy by gradual energy extraction Energy will be put to use to manufacture in ET 33
Electron Transport hain (ET) ET is a series of membrane-bound electron carriers Embedded in the inner mitochondrial membrane Mitochondrial matrix NAD dehydrogenase NAD + + NAD + FAD 2 2 e FAD bc 1 complex ytochrome oxidase complex 2 + + 1 / 2 2 2 Inner mitochondrial membrane Intermembrane space 2 e 2 e + + a. The electron transport chain Q + 34
Electron Transport hain (ET) Electrons from NAD and FAD 2 are transferred to complexes of the ET Each complex A proton pump creating proton gradient Transfers electrons to next carrier Mitochondrial matrix NAD dehydrogenase NAD + + NAD + FAD 2 2 e FAD bc 1 complex ytochrome oxidase complex 2 + + 1 / 2 2 2 Inner mitochondrial membrane Intermembrane space 2 e 2 e + + a. The electron transport chain Q + 35
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Glycolysi s Pyruvate xidatio n Krebs ycle Electron Transport hain hemiosmosis Note that 2 is the final electron acceptor (the reason we require 2 ), combining with protons to form 2 as a byproduct of aerobic respiration. Mitochondrial matrix + NAD dehydrogenase bc 1 complex ytochrome oxidase complex synthase NAD + + NAD + 2 + + 1 / 2 2 2 ADP + P i FAD 2 2 e FAD Inner mitochondrial membrane Intermembrane space 2 e 2 e + + a. The electron transport chain Q + + b. hemiosmosis 36
hemiosmosis Accumulation of protons ( + ) in intermembrane space drives protons into the matrix via diffusion Membrane relatively impermeable to ions Most + can only reenter matrix via synthase Uses energy of gradient to make from ADP + P i Proton Motive Force Mitochondrial matrix NAD + + NAD dehydrogenase NAD + 2 FAD 2 e FAD bc 1 complex ytochrome oxidase complex 2 + + 1 / 2 2 2 synthase + ADP + P i Inner mitochondrial membrane Intermembrane space 2 e 2 e a. The electron transport chain Q + + + + + + + + + + b. hemiosmosis + +
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Mitochondrial matrix + ADP + P i atalytic head Stalk Rotor Intermembrane space + + + + + + 38
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. NAD NAD Glycolysis Glucose Pyruvate Pyruvate xidation Acetyl-oA 2 Note the location of each component of cellular respiration glycolysis, pyruvate oxidation, Krebs cycle and ET e e NAD FAD 2 Krebs ycle 2 2 2 2 + + 1 / 2 2 + 32 e Q + + + Note where the electron carriers transfer electrons 39 from to the ET
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Energy Yield of Respiration Theoretical energy yield (these values vary from book to book) 38 per glucose for bacteria 36 per glucose for eukaryotes Actual energy yield 30 per glucose for eukaryotes Reduced yield is due to Leaky inner membrane Use of the proton gradient for purposes other than synthesis 41
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Glucose 2 2 Glycolysis Pyruvate 2 5 NAD 2.5 s per NAD hemiosmosis Pyruvate oxidation 2 NAD 5 2 Krebs ycle 2.5 s per NAD 6 NAD 15 1.5 s hemiosmosis per FAD 2 2 FAD 2 3 Total net yield = 32 (30 in eukaryotes)?? 42
Regulation of Respiration Glycolysis Glucose ADP Examples of negative feedback inhibition Two key control points 1. In glycolysis Phosphofructokinase is allosterically inhibited by and/or citrate Inhibits Fructose 6-phosphate Phosphofructokinase Fructose 1,6-bisphosphate Pyruvate Pyruvate xidation Pyruvate dehydrogenase Acetyl-oA Krebs ycle itrate Inhibits NAD Activates Inhibits Electron Transport hain and hemiosmosis 43
Regulation of Respiration Glycolysis Glucose ADP Two key control points 2. In pyruvate oxidation Pyruvate dehydrogenase inhibited by high levels of NAD itrate synthetase inhibited by high levels of Inhibits Fructose 6-phosphate Phosphofructokinase Fructose 1,6-bisphosphate Pyruvate Pyruvate xidation Pyruvate dehydrogenase Acetyl-oA Krebs ycle itrate Inhibits NAD Activates Inhibits Electron Transport hain and hemiosmosis 44
Glycolysis Glucose Fructose 6-phosphate ADP Activates Phosphofructokinase Inhibits Fructose 1,6-bisphosphate Inhibits Pyruvate Pyruvate xidation Pyruvate dehydrogenase Acetyl-oA Inhibits Krebs ycle itrate NAD Electron Transport hain and hemiosmosis 45 opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display.
xidation Without 2 1. Anaerobic respiration Use of inorganic molecules (other than 2 ) as final electron acceptor Many prokaryotes use sulfur, nitrate, carbon dioxide or even inorganic metals 2. Fermentation Use of organic molecules as final electron acceptor 46
Anaerobic respiration Methanogens 2 is reduced to 4 (methane) Found in diverse organisms including cows Sulfur bacteria Inorganic sulphate (S 4 ) is reduced to hydrogen sulfide ( 2 S) Early sulfate reducers set the stage for evolution of photosynthesis 47
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Fermentation Reduces organic molecules in order to regenerate NAD + to supply glycolysis allowing it to continue, even in absence of 2 1. Ethanol fermentation occurs in yeast 2, ethanol, and NAD + are produced 2 ADP 2 3 Alcohol Fermentation in Yeast Glucose G L Y L Y S I S 2 Pyruvate 2 NAD + 2 NAD 2 3 2 Ethanol 3 2 Acetaldehyde Lactic Acid Fermentation in Muscle ells 2 AD P Glucose G L 49
Fermentation 2. Lactic acid fermentation Electrons are transferred from NAD to pyruvate to produce lactic acid ccurs in animal cells (especially muscles, such as during sprinting) 2 ADP 2 3 2 AD P 2 2 NAD + 2 NAD 2 Lactic Acid Fermentation in Muscle ells 3 G L Y L Y S I S 2 Pyruvate Glucose G L Y L Y S I S 2 Pyruvate 2 NAD + 2 NAD 3 2 Ethanol 3 2 Acetaldehyde 3 2 Lactate 50
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Alcohol Fermentation in Yeast Glucose 2 ADP 2 G L Y L Y S I S 2 NAD + 2 NAD 3 2 Ethanol 3 2 Pyruvate 2 3 2 Acetaldehyde Lactic Acid Fermentation in Muscle ells 2 AD P 2 Glucose G L Y L Y S I S 2 NAD + 2 NAD 3 2 Lactate 3 2 Pyruvate 51
Anabolic and atabolism Pathways Metabolic pathways are linked to reversible pathways of cellular respiration Large molecules broken down and rearranged catabolic pathways Most larger molecules needed by the cell are produced anabolic pathways 52
Example of atabolism of Protein Amino acids undergo deamination to remove the amino group (-N 2 ) Remainder of the amino acid is converted to a molecule that enters glycolysis or the Krebs cycle Alanine is converted to pyruvate Aspartate is converted to oxaloacetate 2 N Glutamate N 3 Urea α-ketoglutarate 53
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atabolism of Fat Fatty acid Fats are broken down to fatty acids and glycerol Fatty acids are converted to 2- acetyl groups by b-oxidation xygen-dependent process The respiration of a 6-carbon fatty acid yields 20% more energy than 6-carbon glucose Runs in reverse to produce fats Fatty acid 2 shorter oa oa 2 Fatty acid AMP + Fatty acid FAD FAD 2 Fatty acid Fatty acid NAD + NAD Krebs ycle PP i oa oa oa oa Acetyl-oA 55
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Fatty acid oa AMP + Fatty acid PP i oa Fatty acid 2 shorter FAD FAD 2 Fatty acid oa 2 Fatty acid oa oa NAD + NAD Fatty acid oa Acetyl-oA Krebs ycle 56
opyright The McGraw-ill ompanies, Inc. Permission required for reproduction or display. Macromolecule degradation Nucleic acids Proteins Polysaccharides Lipids and fats ell building blocks Nucleotides Amino acids Sugars Fatty acids Deamination Glycolysis b-oxidation xidative respiration Pyruvate Reaction pathways are reversible to make & breakdown most molecules needed by cells Acetyl-oA Krebs ycle Ultimate metabolic products N 3 2 2 57
Evolution of Metabolism ypothetical timeline 1. Ability to store chemical energy in 2. Evolution of glycolysis Pathway found in all living organisms 3. Anaerobic photosynthesis (using 2 S) 4. Use of 2 in photosynthesis (not 2 S) Begins permanent change in Earth s atmosphere about 2.4 Bya 5. Evolution of nitrogen fixation 6. Aerobic respiration evolved most recently 58