2/8/2012 Cellular Respiration Chapter 5 Outline Glycolysis Occurs in a series of reactions: 1. Glycolysis 2. Citric acid cycle (aka TCA or Kreb’s Cycle) 3. Electron transport system Aerobic Respiration Lactic Acid Pathway Glycogenesis, glycogenolysis, gluconeogenesis 2 5-2 General to the Specific Break down of large Molecules to simple molecules Break down simple molecules to Acetyl CoA Oxidation of Acyetl CoA to H20 and CO2 – produce Eand make ATP 5-4 Carbohydrate Catabolism Glycolysis (ATP generated by ETC) (ATP generated by breaking bonds) Figure 24.5 5-5 1 2/8/2012 Glycolysis (General) In glycolysis 2 ATPs are added and 4 are produced for a net gain of 2 ATP Glycolysis (Specific) Event 1 Phosphorylation • Two phosphates added to glucose • Requires ATP Glucose Phase 1 priming Carbon atom P Phosphate 2 ATP 2 ADP Fructose-1,6-diphosphate P P Phase 2 cleavage Event 2 – Splitting (cleavage) • 6-carbon glucose split into two 3-carbon molecules Dihydroxyacetone phosphate Glyceraldehyde phosphate P Phase 3 oxidation and formation of ATP and release of high energy electrons Glyceraldehyde phosphate P P 1 NAD+ 2 ADP 1 NADH + H+ 2 ATP 1 Pyruvic acid 1 Pyruvic acid O2 O22 O 2 NADH + H+ 2 NAD+ To citric acid cycle and electron transport chain (aerobic pathway) 2 Lactic acid 8 5-8 Glycolysis Glycolysis Event 3 – Production of NADH and ATP • H atoms released • Bind to NAD+ to produce NADH • NADH delivers H+ to ETC • ADP is phosphorylated to ATP • 2 pyruvic acid are produced • 2 ATP are generated (4 – 2 [used to start] = 2) Glucose Phase 1 priming Carbon atom P Phosphate 2 ATP 2 ADP Fructose-1,6-diphosphate P P Phase 2 cleavage Dihydroxyacetone phosphate Glyceraldehyde phosphate P Phase 3 oxidation and formation of ATP and release of high energy electrons Glyceraldehyde phosphate P P 2 ADP 1 NAD+ 1 NADH + H+ 2 ATP 1 Pyruvic acid 1 Pyruvic acid O2 O22 O 2 NADH + H+ 2 NAD+ To citric acid cycle and electron transport chain (aerobic pathway) 2 Lactic acid 9 5-9 Aerobic Respiration 5-16 2 2/8/2012 Carbohydrate Catabolism Krebs Cycle (General) In mitochondria matrix Begins with acetyl CoA combining with oxaloacetic acid to form citric acid In a series of reactions citric acid converted back to oxaloacetic acid to complete the pathway Figure 24.5 5-18 Mitochondrial Matrix Reactions (Specific) 6 Cytosol Pyruvic acid from glycolysis Glycolysis Krebs cycle Pyruvic acid (C3) Electron transport chain and oxidative phosphorylation CoA Acetyl CoA CO2 ATP ATP NAD+ CO2 NADH+H+ Mitochondrion (fluid matrix) ATP NAD+ 7 NADH + H+ Acetyl group (C2) 8 Acetyl-Co A Coenzyme A H2O 9 Citric acid (C6) Oxaloacetic acid (C4) H2O 10 NADH + H+ 18 NAD+ (C6) Citric acid cycle NAD+ H2O 11 NADH + H+ (C4) 12 CO2 17 (C5) H2O NAD+ 13 Occurs in mitochondrial matrix (C4) Key: NADH + H+ = Carbon atom 14 16 FADH2 (C4) CO2 FAD Pi = Inorganic phosphate (C4) Pi CoA = Coenzyme A 15 GTP GDP 26-15 ADP Figure 24.7 ATP Pyruvic acid from glycolysis Glycolysis ATP Krebs cycle Electron transport chain and oxidative phosphorylation ATP Cytosol CoA Acetyl CoA NADH+H+ (pickup molecule) Krebs cycle Electron transport chain and oxidative phosphorylation Mitochondrion (fluid matrix) ATP ATP Oxaloacetic acid Cytosol Pyruvic acid from glycolysis Glycolysis NAD+ CO2 ATP NAD+ CO2 CoA Acetyl CoA Oxaloacetic acid Citric acid (pickup molecule) CoA (initial reactant) NADH+H+ Mitochondrion (fluid matrix) ATP Citric acid CoA (initial reactant) Isocitric acid Krebs cycle Krebs cycle Key: Key: = Carbon atom = Carbon atom Pi = Inorganic phosphate Pi = Inorganic phosphate CoA = Coenzyme A CoA = Coenzyme A Figure 24.7 Figure 24.7 3 2/8/2012 Cytosol Pyruvic acid from glycolysis Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation CoA Acetyl CoA ATP ATP (pickup molecule) Electron transport chain and oxidative phosphorylation NAD+ CO2 CoA Acetyl CoA ATP ATP ATP Oxaloacetic acid Krebs cycle Mitochondrion (fluid matrix) NADH+H+ Cytosol Pyruvic acid from glycolysis Glycolysis NAD+ CO2 Mitochondrion (fluid matrix) NADH+H+ ATP Oxaloacetic acid Citric acid (pickup molecule) CoA (initial reactant) Citric acid CoA (initial reactant) Isocitric acid Isocitric acid NAD+ Krebs cycle NAD+ Krebs cycle CO2 CO2 NADH+H+ NADH+H+ a-Ketoglutaric acid a-Ketoglutaric acid CoA NAD+ CO2 Succinyl-CoA Key: NADH+H+ Key: = Carbon atom = Carbon atom Pi = Inorganic phosphate Pi = Inorganic phosphate CoA = Coenzyme A CoA = Coenzyme A Figure 24.7 Cytosol Pyruvic acid from glycolysis Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation (pickup molecule) Electron transport chain and oxidative phosphorylation NAD+ CO2 CoA Acetyl CoA ATP ATP ATP Oxaloacetic acid Krebs cycle Mitochondrion (fluid matrix) NADH+H+ Cytosol Pyruvic acid from glycolysis Glycolysis NAD+ CO2 CoA Acetyl CoA ATP ATP Figure 24.7 Mitochondrion (fluid matrix) NADH+H+ ATP Oxaloacetic acid Citric acid (pickup molecule) CoA (initial reactant) Citric acid CoA (initial reactant) Isocitric acid Isocitric acid NAD+ Krebs cycle NAD+ Krebs cycle CO2 CO2 NADH+H+ NADH+H+ a-Ketoglutaric acid CoA NAD+ CO2 Succinic acid Key: Succinyl-CoA Succinic acid FAD Key: GTP GDP + Pi Succinyl-CoA NADH+H+ CoA = Carbon atom Pi = Inorganic phosphate CoA NAD+ CO2 FADH2 NADH+H+ CoA = Carbon atom a-Ketoglutaric acid Fumaric acid GTP GDP + Pi ADP ATP Pi = Inorganic phosphate CoA = Coenzyme A CoA = Coenzyme A ATP ADP Figure 24.7 Cytosol Pyruvic acid from glycolysis Glycolysis ATP Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP Oxaloacetic acid (pickup molecule) Krebs cycle Electron transport chain and oxidative phosphorylation NAD+ CO2 Mitochondrion (fluid matrix) NADH+H+ Cytosol Pyruvic acid from glycolysis Glycolysis NAD+ CO2 CoA Acetyl CoA ATP Figure 24.7 CoA Acetyl CoA ATP Oxaloacetic acid Citric acid (pickup molecule) NADH+H+ CoA (initial reactant) Mitochondrion (fluid matrix) NADH+H+ ATP Citric acid CoA (initial reactant) NAD+ Isocitric acid Malic acid Isocitric acid Malic acid NAD+ Krebs cycle NAD+ Krebs cycle CO2 CO2 NADH+H+ CO2 FADH2 FAD Key: NADH+H+ a-Ketoglutaric acid Fumaric acid Succinic acid Succinyl-CoA CoA NAD+ FAD Key: GTP GDP + Pi Succinic acid Succinyl-CoA CoA NAD+ NADH+H+ CoA = Carbon atom Pi = Inorganic phosphate CoA = Coenzyme A CO2 FADH2 NADH+H+ CoA = Carbon atom a-Ketoglutaric acid Fumaric acid GTP GDP + Pi ADP ATP Pi = Inorganic phosphate ADP CoA = Coenzyme A ATP Figure 24.7 Figure 24.7 4 2/8/2012 Krebs Cycle Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). 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Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 5-20 Summary of Matrix Reactions Electron Transport Chain 2 pyruvate + 6 H2O 6 CO2 2 ADP + 2 Pi 2 ATP 6 NAD+ + 6 H2 6 NADH + 6 H+ of glucose have all been carried away as CO 2 Also, citric acid cycle is a source of substances for synthesis of fats and nonessential amino acids (later) Relative free energy (kcal/mole) Fe-S 2 FAD + 2 H2 2 FADH2 and exhaled NAD+ FMN (+2 NADH produced during glycolysis) carbon atoms NADH + H+ 50 40 FADH2 FAD Enzyme complex 1 CoQ 30 Cyt b Fe-S Cyt c1 1 20 Enzyme complex 2 Cyt c Cu 10 Cyt a Cyt a3 Enzyme complex 3 0 26-28 26-27 • ADP + P ATP synthase H2O Reaction progress Electron Transport and Oxidative Phosphorylation Electron Transport System NADH and FADH2 carry electrons to the ETS • ETS is a series of electron carriers (proteins) (in cristae of mitochondria) • Energy from electrons transferred to ATP synthase • ATP synthase catalyzes the phosphorylation of ADP to ATP • Water is formed ½ O2 + 2 H+ The electron transport chain is a linked series of proteins on the cristae of mitochondria Proteins are FMN, coenzyme Q, and cytochromes ATP Energy NADH + H+ Energy 2H+ + 2e– NAD+ Energy FADH2 2H+ + 2e– FAD Electron transport chain 2e– 2H+ O2 H2O 29 5-21 5 2/8/2012 Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP ATP Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP ATP H+ H+ H+ Core Intermembrane space Core Intermembrane space Cyt c Cyt c e- Q 1 Q 1 3 3 2 2 Inner mitochondrial membrane Inner mitochondrial membrane NADH + H+ Mitochondrial matrix FADH2 NADH + H+ NAD + e- Mitochondrial matrix Electron Transport Chain FAD NAD + (carrying e from food) Electron Transport Chain Figure 24.8 Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP ATP H+ H+ Figure 24.8 Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP ATP Intermembrane space Cyt c e- eQ 1 H+ H+ Core Intermembrane space FADH2 NADH + H+ Mitochondrial matrix e- eQ 1 3 3 2 Inner mitochondrial membrane FAD FADH2 NADH + H+ NAD + (carrying e from food) FAD NAD + (carrying e from food) Mitochondrial matrix Electron Transport Chain Electron Transport Chain ATP Synthase Figure 24.8 Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP ATP H+ H+ Intermembrane space Q Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation ATP ATP ATP H+ Intermembrane space e- FADH2 NADH + H+ (carrying e from food) Mitochondrial matrix Q 1 3 2 Inner mitochondrial membrane FAD ATP ADP + Pi ATP Synthase Figure 24.8 2 H+ + FADH2 NADH + H+ (carrying e from food) H+ Electron Transport Chain e- e- 3 NAD + Core Cyt c 2 Inner mitochondrial membrane H+ H+ Core Cyt c e- Figure 24.8 H+ H+ H+ 1 Core Cyt c 2 Inner mitochondrial membrane H+ H+ H+ Mitochondrial matrix 1 2 O2 H2O FAD ATP ADP + Pi NAD + H+ Electron Transport Chain ATP Synthase Figure 24.8 6 2/8/2012 Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. ETC Chemiosmotic ATP Synthesis Intermembrane space Matrix Cristae Inner membrane Outer membrane ½ O2 + 2 H+ NADH + H+ NAD+ 6 H+ H2O Matrix 2e– Inner membrane Enzyme complex 1 CoQ 2e– 2e– Enzyme complex 2 Enzyme complex 3 3 ADP + 3 Pi 3 ATP ATP synthase Cyt c Intermembrane space 2 H+ 2 H+ 2 H+ Outer membrane 5-24 ATP Generated by Oxidation of Glucose 26-40 Anaerobic Reactions Glucose 2 Glycolysis ATP (net) 2 NADH + 2 H+ Cytosol 2 pyruvate • If oxygen is not available: • ETC cannot accept electrons from NADH •Pyruvic acid is converted to lactic acid • Glycolysis is inhibited • Less ATP produced CO2 6 NADH + 6 H+ Citric acid cycle 2 ATP Electron-transport chain O2 Carbon atom P Phosphate 2 ATP 2 ADP Fructose-1,6-diphosphate P P Dihydroxyacetone Glyceraldehyde phosphate phosphate P P Phase 3 P oxidation and 1 NAD+ formation of 2 ADP ATP and release 1 NADH + H+ of high energy 2 ATP electrons Pyruvic acid O2 2 FADH2 26-41 Glucose Phase 2 cleavage Mitochondria 2 NADH + 2 H+ Phase 1 priming H2O 4 ATP 28–30 ATP Total 36–38 ATP O2 2 NADH + H+ 2 NAD+ 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) 42 7 2/8/2012 Lactic Acid Pathway Lactic Acid Pathway In absence of O2 - - NADH + H gives its Hs to pyruvic acid creating lactic acid Anaerobic metabolism or Lactic acid fermentation) Only yields a net gain of 2 ATPs per glucose don’t have mitochondria; use only lactic acid pathway Occurs in skeletal and heart muscle when oxygen supply falls below critical level During heavy exercise or vascular blockage RBCs 5-10 5-11 Glycogenesis and Glycogenolysis Break down of large Molecules to simple molecules For osmotic reasons cells can’t store lots of free glucoses in cells – we change it to glycogen Glycogen = polymers of glucose Glucose to Glycogen = (Glycogenesis) Place a P group on glucose and take it back off Polymerizes glucose to glycogen Skeletal muscle & liver store glycogen Glycogenolysis = glycogen to glucose Add the P back to Glucose (glucose 6 phosphate) Most cells can use for glycolysis If P attached to Glucose – it can’t leave cell Break down simple molecules to Acetyl CoA Oxidation of Acyetl CoA to H20 and CO2 – produce Eand make ATP 5-12 Cori Cycle Glycogenesis and Glycogenolysis Skeletal muscles use trapped glucose-6phosphate for own energy needs - i.e., uses it for glycolysis - cannot release into blood glycogenisis Some skeletal muscle lactic acid goes to liver Gluconeogenesis: convert non-carb molecules (e.g. lactic acid) back through pyruvic acid to glucose and glycogen Glycogenolysis (Glycogen synthase) (glycogen phosphorylase) Glucose-6 phosphotase Only liver has glucose-6phosphatase that removes phosphate groups So it can secrete free glucose into blood Rule to remember - - Org. molecules w/ phosphate groups can not pass through plasma membrane (Lactic acid dehydrogenase) 5-14 5-15 8