Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Electrons from food 2e– Oxidation Energy-rich Energy released Product molecule Reduction for ATP synthesis Enzyme H H High energy +H+ H H 2e– H H H+ H H + NAD NAD+ NAD NAD NAD+ Low energy 1. Enzymes that use NAD+ 2. In an oxidation–reduction 3. NADH diffuses away as a cofactor for oxidation reaction, 2 electrons and and can then donate reactions bind NAD+ and the a proton are transferred electrons to other + 1 2H /2 O2 substrate. to NAD+, forming NADH. molecules. A second proton is donated to the solution. H2O 1 2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reduction + 2H H Oxidation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. PEP Pyruvate P P Enzyme Enzyme P P P – ADP P – ATP Adenosine Adenosine 3 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis ATP NADH Outer Glycolysis Pyruvate Oxidation mitochondrial membrane Glucose Intermembrane Krebs Cycle space NADH ATP Electron Transport Chain Chemiosmosis Pyruvate STEP A 6-carbon glucose Glycolysis begins (Starting material) with the addition of energy. Two high- energy phosphates ATP ATP (P) from two Pyruvate molecules of ATP are added to the ADP ADP Oxidation Mitochondrial 6-carbon molecule glucose, producing matrix Priming Reactions a 6-carbon molecule with two P P NADH CO2 phosphates. Acetyl-CoA 6-carbon sugar diphosphate STEP B Then, the 6-carbon molecule with two phosphates is split in two, forming two NADH CO2 3-carbon sugar phosphates. Cleavage Krebs P P Cycle FADH2 ATP Inner 3-carbon sugar 3-carbon sugar STEPS C and D phosphate phosphate An additional mitochondrial P P Inorganic phosphate – i i e ( Pi ) is incorporated membrane + + + H O NAD NAD into each 3-carbon NAD FAD O2 2 ATP sugar phosphate. An NADH NADH oxidation reaction converts the two sugar phosphates – ADP ADP e Electron e– Chemiosmosis into intermediates that can transfer a phosphate to ADP to Transport Chain ATP Synthase ATP ATP form ATP. The oxidation reactions + ADP ADP also yield NADH H giving a net energy yield of 2 ATP and 2 Oxidation and ATP Formation ATP and Oxidation NADH. ATP ATP 3-carbon 3-carbon pyruvate pyruvate 5 6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis CH2OH ATP Glycolysis: The Reactions O NADH Glucose Pyruvate Oxidation Glucose Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 ATP CH O P Hexokinase 2 Krebs ADP O Without oxygen Cycle Glucose 6-phosphate Glucose 6-phosphate Phosphoglucose Electron Transport Chain 2 isomerase CH O P Chemiosmosis 2 Pyruvate O CH OH Fructose 6-phosphate 2 Fructose ATP 3 6-phosphate With oxygen Phosphofructokinase H O 1. Phosphorylation of ADP P O CH2 CH2 O P 2 + NAD CO glucose by ATP. 2 O Fructose 1,6-bisphosphate 2–3. Rearrangement, Fructose 4 5 followed by a second Aldolase ATP phosphorylation. Isomerase 1,6-bisphosphate 4–5. The 6-carbon molecule P O CH2 H Dihydroxyacetone Glyceraldehyde 3- is split into two 3-carbon phosphate phosphate (G3P) C O C O O NADH NADH molecules—one G3P, 2 Acetaldehyde another that is converted CH OH CHOH 6 2 into G3P in another 3-phosphate P Glyceraldehyde O reaction. NAD+ P P NAD+ CH2 i i Dihydroxyacetone Phosphate NADH Glyceraldehyde NADH ETC in mitochondria 6. Oxidation followed by phosphorylation produces 3-phosphate P O C O two NADH molecules and dehydrogenase + CHOH Acetyl-CoA NAD NADH two molecules of BPG, 1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate (BPG) each with one (BPG) glycerate CH2 O P high-energy phosphate 1,3-Bisphospho- bond. ADP 7 ADP O– 7. Removal of high-energy Phosphoglycerate ATP ATP C O phosphate by two ADP kinase molecules produces two + 3-Phosphoglycerate 3-Phosphoglycerate CHOH NAD glycerate ATP molecules and leaves 3-Phospho- Lactate two 3PG molecules. (3PG) (3PG) CH O P 2 8 8–9. Removal of water yields O– two PEP molecules, each Phosphoglyceromutase with a high-energy C O phosphate bond. Krebs H C O P glycerate 2-Phosphoglycerate 2-Phosphoglycerate 2-Phospho- 10. Removal of high-energy (2PG) (2PG) CH2OH Cycle phosphate by two ADP molecules produces two 9 O– ATP molecules and two H O H O 2 Enolase 2 C O Ethanol C O P pyruvate Phosphoenolpyruvate Phosphoenolpyruvate (PEP) (PEP) Phosphoenol- CH2 O– ADP 10 ADP C O Pyruvate kinase ATP ATP C O Pyruvate Pyruvate Pyruvate CH 3 7 8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis Glycolysis Pyruvate Oxidation Pyruvate Oxidation CoA- (Acetyl-CoA) CoA NADH NADH Krebs 4-carbon ATP Krebs Cycle molecule FADH Cycle 2 (oxaloacetate) 6-carbon molecule Electron Transport Chain NADH (citrate) Chemiosmosis NAD + Electron Transport Chain SEGMENT A Chemiosmosis NADH NAD+ SEGMENT A CO Pyruvate from glycolysis is 2 SEGMENT C oxidized into an acetyl group that Pyruvate Oxidation: The Reaction feeds into the citrate cycle. 2-C 4-carbon – acetyl group combines with 4-C O molecule Krebs Cycle 5-carbon oxaloacetate to produce the 6-C molecule C O compound citrate. Pyruvate ⎯ NAD+ C ⎯ O FADH Pyruvate ⎯ SEGMENT B 2 Oxidation reactions produce CO CH 3 2 NADH. The loss of two CO2's NADH leaves a new 4-C compound. 1 NAD+ ATP is directly generated for FAD SEGMENT B each acetyl group fed in. NADH CO2 4-carbon CoA S CoA 4-carbon SEGMENT C molecule molecule Two additional oxidations C ⎯ O generate another NADH and an FADH and regenerate the CH 2 Acetyl Coenzyme A 3 original 4-C oxaloacetate. ATP ADP + P Acetyl Coenzyme A A Acetyl Coenzyme 9 10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis 1. Reaction 1: Condensation Pyruvate Oxidation 2–3. Reactions 2 and 3: Isomerization 4. Reaction 4: The first oxidation Glycolysis NADH 5. Reaction 5: The second oxidation Krebs ATP Cycle 6. Reaction 6: Substrate-level phosphorylation FADH 2 7. Reaction 7: The third oxidation Pyruvate Oxidation Electron T ransport Chain Chemiosmosis 8–9. Reactions 8 and 9: Regeneration of oxaloacetate and the fourth oxidation Krebs Cycle: The Reactions Krebs Acetyl-CoA Cycle ATP O — CoA ═ Oxaloacetate (4C) CH3— C— S NADH — Citrate (6C) COO — — CoA-SH COO Electron Transport Chain + NAD O ═ C 1 — — Malate (4C) CH 2 Chemiosmosis CH Citrate — 2 — COO — synthetase — 9 HO— C — COO — COO— — HO— CH Malate CH — dehydrogenase 2 — CH 2 — + COO + — H COO— ATP 2 Mitochondrial matrix H2O Aconitase 3 Cytochrome ATP 8 Fumarase NADH dehydrogenase bc1 complex oxidase complex synthase Fumarate (4C) Isocitrate (6C) ADP + Pi — COO — + 1 COO + + H O NADH + H NAD 2H + /2O 2 2 — CH — CH 2 ═ FADH — 2 HC — HC — COO — — – COO— HO — CH 2 e FAD — — FADH2 COO – 22 – Succinate Isocitrate e 22 e FAD 7 dehydrogenase dehydrogenase 4 NAD+ Q Succinate (4C) CO2 COO— NADH C — Inner CH 2 -Ketoglutarate (5C) — α mitochondrial CH CoA-SH 2 — COO — + — Succinyl-CoA (4C) membrane H + COO Succinyl-CoA — H + CO + H — 2 CH 2 H synthetase COO — GTP — -Ketoglutarate α CH CH 2 Intermembrane space 6 2 dehydrogenase — ADP — C — O GDP + P CH i 2 + 5 NAD — — COO— a. The electron transport chain b. Chemiosmosis C ═ O ATP — CoA-SH S — CoA NADH 11 12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis + H NADH Glucose Mitochondrial 2 ATP matrix Pyruvate ATP Pyruvate NADH Oxidation CO2 ADP+Pi Acetyl-CoA Catalytic head NADH CO2 + H Krebs - e Cycle 32 ATP FADH2 2 ATP - e + Stalk 2H H O + 2 1 /2 O2 - e Q C + H + Rotor H + H + + H H + Intermembrane + H H space + + H H 13 14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis Glucose ADP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Activates Glucose Fructose 6-phosphate 2 ATP 2 ATP Glycolysis Phosphofructokinase Pyruvate 2 NADH 6 ATP Fructose 1,6-bisphosphate Inhibits Inhibits Chemiosmosis Pyruvate Pyruvate oxidation 2 NADH 6 ATP Pyruvate Oxidation 2 ATP Pyruvate dehydrogenase ATP Acetyl-CoA Krebs Inhibits 6 NADH 18 Cycle ATP Citrate Chemiosmosis Krebs Cycle 2 FADH2 4 ATP NADH Total net ATP yield = 38 Electron Transport Chain (36 in eukaryotes) and Chemiosmosis 15 16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Alcohol Fermentation in Yeast H Macromolecule degradation Nucleic acids Proteins Polysaccharides Lipids and fats H C OH 2 ADP CH3 2 Ethanol 2 NAD+ Cell building blocks 2 ATP Nucleotides Amino acids Sugars Fatty acids 2 NADH – O H Glycolysis Deamination β-oxidation C O C O CO C O 2 CH3 Oxidative respiration CH3 2 Acetaldehyde Pyruvate Lactic Acid Fermentation in Muscle Cells – Acetyl-CoA O C O 2 ADP H C OH 2 ATP CH3 Krebs 2 Lactate 2 NAD+ Cycle – O 2 NADH C O Ultimate metabolic products C O NH3 H2O CO2 CH3 17 18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urea NH3 19 .