Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Product Enzyme NAD + NAD 2e – H+H+ +H + Energy-rich molecule 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 NADH. A second proton is donated to the solution. 3. NADH diffuses away and can then donate electrons to other molecules. ReductionOxidation H H H H H H H H 1

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2e – Electrons from food High energy Low energy 2H + 1 / 2 O2O2 Energy released for ATP synthesis H2OH2O 2

2HH+H+ Reduction Oxidation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3

– ADP Enzyme – ATP PEP Adenosine Pyruvate P P P P P P P P P P Adenosine P P 4

Outer mitochondrial membrane Intermembrane space Mitochondrial matrix CO 2 ATP H2OH2O FAD O2O2 Inner mitochondrial membrane Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ATP e–e– Electron Transport Chain Chemiosmosis ATP Synthase e–e– H+H+ e–e– NAD + NADH Glycolysis Pyruvate Glucose Pyruvate Oxidation Acetyl-CoA NADH Krebs Cycle CO 2 ATP NADH FADH 2 5

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis NADH Pyruvate Oxidation ATP Electron Transport Chain Chemiosmosis Krebs Cycle 6-carbon sugar diphosphate NAD + Priming Reactions Cleavage Oxidation and ATP Formation STEPS C and D NADH PP P P STEP A ATP ADP STEP B 3-carbon sugar phosphate 3-carbon sugar phosphate PiPi PiPi ADP ATP ADP ATP 3-carbon pyruvate 3-carbon pyruvate 6-carbon glucose (Starting material) Glycolysis begins with the addition of energy. Two high- energy phosphates (P) from two molecules of ATP are added to the 6-carbon molecule glucose, producing a 6-carbon molecule with two phosphates. Then, the 6-carbon molecule with two phosphates is split in two, forming two 3-carbon sugar phosphates. 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 ATP. The oxidation reactions also yield NADH giving a net energy yield of 2 ATP and 2 NADH. 6

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. NADH NAD+ NADH PiPi NAD+ Glucose Hexokinase Phosphofructokinase Glucose 6-phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate Isomerase Aldolase Pyruvate Enolase Pyruvate kinase ADP 10 Glucose Glyceraldehyde 3-phosphate Pyruvate Glycolysis: The Reactions Glycolysis NADH Pyruvate Oxidation H2OH2O ATP ADP Electron Transport Chain Chemiosmosis Krebs Cycle ATP Phosphoglucose isomerase Glyceraldehyde 3- phosphate (G3P) Dihydroxyacetone phosphate 1. Phosphorylation of glucose by ATP. 2–3. Rearrangement, followed by a second ATP phosphorylation. 4–5. The 6-carbon molecule is split into two 3-carbon molecules—one G3P, another that is converted into G3P in another reaction. 6. Oxidation followed by phosphorylation produces two NADH 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 ATP molecules and leaves two 3PG molecules. 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 ATP molecules and two 1,3-Bisphosphoglycerate (BPG) 1,3-Bisphosphoglycerate (BPG) Glyceraldehyde 3-phosphate dehydrogenase PiPi ADP Phosphoglycerate kinase ADP ATP 3-Phosphoglycerate (3PG) 3-Phosphoglycerate (3PG) 2-Phosphoglycerate (2PG) 2-Phosphoglycerate (2PG) H2OH2O ATP Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) ADP ATP Phosphoenol- pyruvate 3-Phospho- glycerate 1,3-Bisphospho- glycerate Glucose 6-phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate Dihydroxyacetone Phosphate 2-Phospho- glycerate CH 2 OH O CH 2 O O P O O P CH 2 OH OCH 2 O O PP CHOH H CO CH 2 O P CO O P CH 2 OH CHOH OCO CH 2 O P P CHOH O–O– CO CH 2 O P H C O O–O– CO CH 2 OH P CO O–O– CO CH 2 P CO O–O– CO CH Phosphoglyceromutase 7

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Without oxygen NAD + O2O2 NADH ETC in mitochondria Acetyl-CoA Ethanol NAD + CO 2 NAD + H2OH2O Lactate Pyruvate Acetaldehyde NADH With oxygen Krebs Cycle 8

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis Pyruvate Oxidation NADH Krebs Cycle Electron Transport Chain Chemiosmosis Pyruvate Oxidation: The Reaction NAD + CO 2 CoA Acetyl Coenzyme A Pyruvate Acetyl Coenzyme A O CH 3 C O–O– C  O     S CoA CH 3 OC   NADH 9

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. SEGMENT A Pyruvate from glycolysis is oxidized into an acetyl group that feeds into the citrate cycle. 2-C acetyl group combines with 4-C oxaloacetate to produce the 6-C compound citrate. SEGMENT B Oxidation reactions produce NADH. The loss of two CO 2 's leaves a new 4-C compound. 1 ATP is directly generated for each acetyl group fed in. CoA- (Acetyl-CoA) CoA 4-carbon molecule (oxaloacetate) 6-carbon molecule (citrate) NAD + NADH CO 2 5-carbon molecule NAD + NADH CO 2 4-carbon molecule ADP + P Krebs Cycle FAD FADH 2 4-carbon molecule NAD + NADH SEGMENT C Two additional oxidations generate another NADH and an FADH 2 and regenerate the original 4-C oxaloacetate. ATP Glycolysis Pyruvate Oxidation Electron Transport Chain Chemiosmosis NADH FADH 2 Krebs Cycle ATP SEGMENT A SEGMENT B SEGMENT C 4-carbon molecule 10

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis NADH FADH 2 Pyruvate Oxidation ATP Krebs Cycle: The Reactions Citrate synthetase NAD + NADH H2OH2O NAD + NADH CO 2 FAD Isocitrate dehydrogenase Fumarase CoA-SH 1 2 Aconitase CoA-SH NAD + CO NADH CoA-SH GDP + P i Acetyl-CoA ═ CH 3 — C — S OCoA — Krebs Cycle Malate dehydrogenase  -Ketoglutarate dehydrogenase Succinyl-CoA synthetase GTP ATP ADP Succinate dehydrogenase FADH 2 8–9. Reactions 8 and 9: Regeneration of oxaloacetate and the fourth oxidation 7. Reaction 7: The third oxidation 6. Reaction 6: Substrate-level phosphorylation 5. Reaction 5: The second oxidation 4. Reaction 4: The first oxidation 2–3. Reactions 2 and 3: Isomerization 1. Reaction 1: Condensation Electron T ransport Chain Chemiosmosis Oxaloacetate (4C) CH 2 O ═ C COO — — — — Citrate (6C) HO — C — COO — CH 2 — — — — Isocitrate (6C) HC — COO — CH 2 HO — CH — — — —  -Ketoglutarate (5C) CH 2 COO — CH 2 C — O — — — — Succinyl-CoA (4C) CH 2 COO — S — CoA CH 2 C ═ O — — — — Succinate (4C) COO — CH 2 COO — CH 2 — — — Fumarate (4C) HC CH ═ COO — — — Malate (4C) HO — CH COO — CH 2 COO — — — — 11

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mitochondrial matrix NADH + H + ADP + P i H2OH2O H+H+ H+H+ 2H / 2 O2O2 Glycolysis Pyruvate Oxidation 2 Krebs Cycle ATP Electron Transport Chain Chemiosmosis NADH dehydrogenase bc 1 complex Cytochrome oxidase complex FAD Inner mitochondrial membrane Intermembrane space a. The electron transport chain ATP synthase ATP b. Chemiosmosis NAD + Q C e–e– FADH 2 H+H+ H+H+ H+H+ H+H+ e–e– 2 2 e–e–

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ADP+P i Catalytic head Stalk Rotor H+H+ H+H+ Mitochondrial matrix Intermembrane space H+H+ H+H+ H+H+ H+H+ H+H+ ATP 13

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H2OH2O CO 2 H+H+ H+H+ 2H / 2 O2O2 H+H+ e-e- H+H+ 32 ATP Krebs Cycle 2 ATP NADH FADH 2 NADH Pyruvate Oxidation Acetyl-CoA e-e- Q C e-e- Glycolysis Glucose Pyruvate 2 ATP 14

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemiosmosis NADH Total net ATP yield = 38 (36 in eukaryotes) ATP Krebs Cycle Pyruvate oxidation FADH 2 Glycolysis 2 Glucose Pyruvate ATP 15

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glucose Acetyl-CoA Fructose 6-phosphate Fructose 1,6-bisphosphate Pyruvate Pyruvate Oxidation Krebs Cycle Electron Transport Chain and Chemiosmosis Citrate ADP ATP NADH Inhibits Activates Inhibits Phosphofructokinase Pyruvate dehydrogenase Glycolysis 16

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CO 2 2Acetaldehyde 2ADP 2 Lactate Alcohol Fermentation in Yeast 2 ADP Lactic Acid Fermentation in Muscle Cells 2 NAD + 2 NADH 2 ATP CO CO O–O– CH 3 CO H CO CO O–O– HCOH CO O–O– H 2 Ethanol HCOH CH 3 17

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell building blocks Deamination  -oxidation Glycolysis Oxidative respiration Ultimate metabolic products Acetyl-CoA Pyruvate Macromolecule degradation Krebs Cycle Nucleic acidsPolysaccharides NucleotidesAmino acidsFatty acidsSugars ProteinsLipids and fats NH 3 H2OH2OCO 2 18

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urea NH 3 19