Electrons from Food High Energy Low Energy 2H+ Energy Released for ATP Synthesis

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

Reduction

PEP Pyruvate

P Enzyme Enzyme P P

P – ADP P – ATP Adenosine Adenosine

3 4

NADH Outer Glycolysis Pyruvate Oxidation mitochondrial membrane Glucose Intermembrane Krebs Cycle NADH ATP space 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 Reactions Priming a 6-carbon molecule with two CO P P phosphates. NADH Acetyl-CoA 2

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 Cycle P P 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 NAD+ NAD+ NAD+ FAD O H2O ATP into each 3-carbon 2 sugar phosphate. An NADH NADH oxidation reaction converts the two sugar phosphates – ADP ADP e Electron e– Chemiosmosis into intermediates that can transfer a Transport Chain ATP Synthase ATP ATP phosphate to ADP to 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 Formation ATP and Oxidation NADH. ATP ATP

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 6-phosphate Phosphoglucose Electron Transport Chain 2 isomerase CH O P Chemiosmosis 2 Pyruvate O CH2OH Fructose 6-phosphate Fructose ATP 3 6-phosphate With oxygen Phosphofructokinase 1. Phosphorylation of O CH CH O H O + ADP P 2 2 P 2 NAD CO glucose by ATP. 2 O Fructose 1,6-bisphosphate

2–3. Rearrangement, Fructose 4 5 followed by a second Aldolase

1,6-bisphosphate ATP phosphorylation. Isomerase P CH H 4–5. The 6-carbon molecule Dihydroxyacetone Glyceraldehyde 3- O 2 is split into two 3-carbon phosphate phosphate (G3P) O NADH molecules—one G3P, C O C O 2 NADH Acetaldehyde another that is converted CH OH CHOH 6 2 into G3P in another 3-phosphate 3-phosphate P Glyceraldehyde CH O reaction. NAD+ P P NAD+ 2 i i Dihydroxyacetone Phosphate ETC in mitochondria 6. Oxidation followed by NADH Glyceraldehyde NADH phosphorylation produces 3-phosphate P O C O two NADH molecules and dehydrogenase NAD+ NADH two molecules of BPG, 1,3-Bisphosphoglycerate CHOH Acetyl-CoA 1,3-Bisphosphoglycerate (BPG) each with one glycerate (BPG) CH O P 2 high-energy phosphate 1,3-Bisphospho- 1,3-Bisphospho- bond. ADP 7 ADP O– 7. Removal of high-energy ATP Phosphoglycerate ATP kinase C O phosphate by two ADP + molecules produces two CHOH NAD 3-Phosphoglycerate 3-Phosphoglycerate ATP molecules and leaves glycerate

3-Phospho- 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 CH OH (2PG) (2PG) 2 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 Phosphoenol- Phosphoenol- CH (PEP) (PEP) 2 O– ADP 10 ADP

C O ATP Pyruvate kinase ATP C O Pyruvate Pyruvate Pyruvate CH 3 7 8

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 AcetylCoenzyme 9 10

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 + Pi CH 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

C + H + Rotor H + H

+ + H H + Intermembrane + H H space + + H H 13 14

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

Urea

NH3