Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CHAPTER 7 LECTURE SLIDES Prepared by Brenda Leady University of Toledo To run the animations you must be in Slideshow View. Use the buttons on the animation to play, pause, and turn audio/text on or off. Please note: once you have used any of the animation functions (such as Play or Pause), you must first click in the white background before you advance the next slide.

2 Cellular respiration Process by which living cells obtain energy from organic molecules Primary aim to make ATP and NADH Aerobic respiration uses oxygen  O 2 consumed and CO 2 released Focus on glucose but other organic molecules also used

3 Glucose metabolism C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O 4 metabolic pathways 1. Glycolysis- Substrate level phosphorylation 2. Breakdown of pyruvate to an acetyl group 3. Citric acid cycle 4. Oxidative phosphorylation

4 1 2 pyruvate CCCCCC CCC acetyl CCC 2 CC 2 2 pyruvate 2 CO CO 2 C C 2 2 acetyl Cytosol 2 NADH 2 +2 ATP Via chemiosmosis 6 NADH 2 FADH 2 Glycolysis: Glucose Outer mitochondrial membrane Breakdown of pyruvate: 2CO 2 + 2acetyl Citric acid cycle: Via substrate-level phosphorylation Via substrate-level phosphorylation Mitochondrial matrix Inner mitochondrial membrane +2 ATP +30–34 ATP 4 Oxidative phosphorylation: The oxidation of NADH and FADH 2 via the electron transport chain provides energy to make more ATP via the ATP synthase. O 2 is consumed. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

5 Stage 1: Glycolysis Glycolysis can occur with or without oxygen Steps in glycolysis nearly identical in all living species 10 steps in 3 phases 1. Energy investment 2. Cleavage 3. Energy liberation

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7 3 phases of glycolysis 1. Energy investment  Steps 1-3  2 ATP hydrolyzed to create fructose-1,6 bisphosphate 2. Cleavage  Steps 4-5  6 carbon molecule broken into two 3 carbon molecules of glyceraldehyde-3-phosphate 3. Energy liberation  Steps 6-10  Two glyceraldehyde-3-phosphate molecules broken down into two pyruvate molecules producing 2 NADH and 4 ATP Net yield in ATP of 2

8 CCCCCC Glucose OHH H H O HH HO CH 2 OH Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

9 ATP CCCCCC CCCCCC Energy investment phase Step 2Step 3Step 1 Glucose Fructose-1,6- bisphosphate OHH H H O HH HO CH 2 OH H HO OH H H OCH 2 PP O CH 2 O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

10 CC C ATP CCCCCC CCCCCC CCC Cleavage phaseEnergy investment phase Step 4 Step 5 Step 2Step 3Step 1 Glucose Fructose-1,6- bisphosphate OHH H H O HH HO CH 2 OH ATP H HO OH H H OCH 2 PP O CH 2 O P CHOH C H O CH 2 O P CHOH H OC CH 2 O Two molecules of glyceraldehyde- 3-phosphate Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

11 CC C PiPi ATP NADH ATP NADH ATP CCCCCC CCCCCC CCC CCC CC C CO CO O–O– CH 3 CO CO O–O– Cleavage phaseEnergy investment phase Step 4 Step 5 Step 6 Step 7Step 8Step 9Step 10 Energy liberation phase Step 2Step 3Step 1 Glucose Fructose-1,6- bisphosphate OHH H H O HH HO CH 2 OH H HO OH H H OCH 2 PP O CH 2 O P CHOH C H O CH 2 O PiPi Two molecules of pyruvate P CHOH H OC CH 2 O Two molecules of glyceraldehyde- 3-phosphate Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

12 H+H+ OC O–O– CH 3 O C NADH + NAD + ++ CoASH CO 2 Acetyl CoA Outer membrane channel H + /pyruvate symporter Pyruvate dehydrogenase O CoA C S CH 3 + OC O–O– O C Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

13 Stage 3: Citric acid cycle Metabolic cycle  Particular molecules enter while other leave, involving a series of organic molecules regenerated with each cycle Acetyl is removed from Acetyl CoA and attached to oxaloacetate to form citrate or citric acid Series of steps releases 2CO 2, 1ATP, 3NADH, and 1 FADH 2 Oxaloacetate is regenerated to start the cycle again

14 Citric acid cycle GTP ATP 5 NADH CO CCCCC 1 2 CCCC NADH 8 CCCC 7 CCCC FADH 2 6 CCCC +2 ATP 2 CO 2 2 NADH 6 NADH2 FADH 2 2 CO ATP 2 pyruvate CCCC +30–34 ATP CCCCCC CCCCCC NADH Acetyl CoA Oxaloacetate Citrate Glycolysis: Glucose Break- down of pyruvate Oxidative phosphorylation O CSCoAH2CH2C Citric acid cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

15 Stage 4: Oxidative phosphorylation High energy electrons removed from NADH and FADH 2 to make ATP Typically requires oxygen Oxidative process involves electron transport chain Phosphorylation occurs by ATP synthase

16 Oxidation: ETC Electron transport chains (ETC)  Group of protein complexes and small organic molecules embedded in the inner mitochondrial membrane Can accept and donate electrons in a linear manner in a series of redox reactions Movement of electrons generates H + electrochemical gradient/ proton-motive force  Excess of positive charges outside of matrix

17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. NAD + c I III II IV H2OH2O Q Matrix + NADH dehydrogenase Ubiquinone Cytochrome b-c 1 Cytochrome c Cytochrome oxidase ATP synthase Succinate reductase Inner mitochondrial membrane ATP synthesis Electron transport chain Intermembrane space movement e–e– KEY H+H+ NADH FAD + 2 H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H - - FADH 2 ADP + P i H+H+ 2 H + + ½ O 2 ATP Matrix Intermembrane space

Phosphorylation: ATP synthase Lipid bilayer of inner mitochondrial membrane relatively impermeable to H + Can only pass through ATP synthase Harnesses free energy release to synthesize ATP from ADP Chemiosmosis- chemical synthesis of ATP as a result of pushing H + across a membrane 18

19 NADH oxidation and ATP synthesis Oxidation of NADH results in electrochemical gradient used to synthesize ATP ATP molecules per glucose molecule broken down into CO 2 and H 2 O Rarely achieve maximal amount  NADH used in anabolic pathways  H + gradient used for other purposes

20 ATP synthase Enzyme harnesses free energy as H + flow through membrane embedded region Energy conversion- H + electrochemical gradient or proton motive force converted to chemical bond energy in ATP Racker and Stoeckenius confirmed ATP uses an H + electrochemical gradient Rotary machine that makes ATP as it spins

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Cancer cells usually favor glycolysis Many disease associated with alterations in carbohydrate metabolism Warburg effect- cancer cells preferentially use glycolysis while decreasing oxidative phosphorylation Used to diagnose cancers in PET scans Glycolytic enzymes overexpressed in 80% of all types of cancers Caused by genetic and environmental factors- mutations and low oxygen

24 Other organic molecules Focus on glucose but other carbohydrates, proteins and fats also used for energy Enter into glycolysis or citric acid cycle at different points Utilizing the same pathways for breakdown increases efficiency Metabolism can also be used to make other molecules (anabolism)

25 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proteins Carbohydrates Fats Sugars Pyruvate Acetyl CoA Amino acids Glycolysis: Glucose Glyceraldehyde- 3-phosphate Citric acid cycle Oxidative phosphorylation Glycerol Fatty acids © The McGraw-Hill Companies, Inc./Ernie Friedlander/Cole Group/Getty Images

26 Anaerobic metabolism For environments that lack oxygen or during oxygen deficits 2 strategies  Use substance other than O 2 as final electron acceptor in electron transport chain  Produce ATP only via substrate-level phosphorylation

Fermentation Many organisms can only use O 2 as final electron acceptor Make ATP via glycolysis only Need to regenerate NAD + to keep glycolysis running Muscle cells produce lactate Yeast make ethanol Produces far less ATP 27

28 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) Production of lactic acid(b) Production of ethanol 2 lactate (secreted from the cell) 2 H 1 2 NAD H + 2 NADH 2 ATP 2 ethanol (secreted from the cell)2 acetaldehyde 2 H + 2 pyruvate 2 NAD H + 2 NADH GlycolysisGlucose 2 pyruvate 2 ATP GlycolysisGlucose O OC O—O— C CH 3 O HOHC C O—O— CH P i 2 ADP O OC O—O— C CH 3 2 CO 2 HOHC H CH 3 OC H (weights): © Bill Aron/Photo Edit; (wine barrels): © Jeff Greenberg/The Image Works + 2 P i 2 ADP