1. Chapter 8: Cellular Respiration (Outline)
NAD+ and FAD
Phases of Cellular Respiration
Glycolysis
Preparatory (prep) Reaction
Citric Acid Cycle
Electron Transport System (ETC)
Fermentation
Catabolic and Anabolic Reactions

2. Cellular Respiration
A cellular process that requires oxygen and gives off carbon dioxide
Usually involves breakdown of glucose to carbon dioxide and water
Energy extracted from glucose molecule:
Released slowly step-wise
Allows ATP to be produced efficiently
Oxidation-reduction enzymes include NAD+ and FAD as coenzymes

3. Cellular Respiration
Glucose is oxidized and thus releases energy, while oxygen is reduced to form water
The carbon atoms of the sugar molecule are released as carbon dioxide (CO2)
Glucose is high-energy molecule; CO2 and H2O are low-energy molecules thus energy is released

4. Cellular Respiration
Cells carry out cellular respiration in order to build up ATP molecules
Energy is released slowly, step-wise, through many enzymatic reactions in different parts of the cell, why?
Breakdown of glucose realizes a maximum yield of 36 or 38 ATP; this preserves 39% of energy available in glucose

5. NAD+ and FAD
Each metabolic reaction in cellular respiration is catalyzed by its own enzyme
NAD+ is a redox coenzyme that can
Oxidize a metabolite by accepting two electrons and a hydrogen ion; results in NADH
Reduce a metabolite by giving up electrons
FAD is another redox coenzyme
Sometimes used instead of NAD+
Accepts two electrons and two hydrogen ions (H+) to become FADH2

6. NAD+ and FAD
Electrons received by NAD+ and FAD are high-energy electrons and are usually carried to the electron transport system
Only a small amount of NAD+ is needed in cells, because each NAD+ molecule is used over & over again

7. Phases of Cellular Respiration
Cellular respiration involves four phases
Glycolysis:
Occurs in the cytoplasm
Does not require oxygen; occurs under aerobic or anaerobic conditions
Glucose broken down into two 3-carbon molecules of pyruvate
Enough energy is released for immediate buildup of two ATP molecules

8. Phases of Cellular Respiration
Preparatory (Prep) reaction:
Takes place inside the mitochondrion
Pyruvate is oxidized to a 2-carbon (C2) acetyl group
Electron energy is stored in NADH
CO2 is released as waste product
Occurs twice per glucose molecule

9. Phases of Cellular Respiration
Citric acid cycle:
Series of oxidation reactions occurring in the matrix of mitochondrion (i.e. aerobic)
Electron energy is stored in NADH and FADH2
Produces two immediate ATP molecules per glucose molecule
Four carbons are released as CO2
The cycle turns twice per glucose molecule

10. Phases of Cellular Respiration
Electron transport chain:
A series of carriers on the cristae of the mitochondria
Extracts energy from NADH & FADH2
Electrons pass from higher to lower energy states, energy is released and stored for ATP production, how?
Produces 32 or 34 molecules of ATP per glucose molecule

11. Glucose Breakdown: Overview of the Four Phases

12. Pyruvate Pyruvate is a pivotal metabolite in cellular respiration
If O2 is not available to the cell, fermentation, an aerobic process, occurs
During fermentation, glucose is incompletely metabolized to lactate or CO2 and alcohol
Fermentation results in a net gain of only two ATP per glucose molecule

13. Glucose Breakdown: Glycolysis
Proceeds in the cytosol
Occurs universally in organisms (i.e. most likely evolved before the citric acid cycle and the electron transport system)
Energy Investment Steps:
The addition of two phosphate groups from ATP to activate glucose in 2 separate reactions
Glucose splits into two (C3) G3P molecules, each with a phosphate group
glucose + 2 ATP → 2 G3P + 2 ADP

14. Glycolysis Energy Harvesting Steps:
In duplicated reactions, NAD+ accepts two electrons and one H+ ion resulting in two NADH
Four ATP molecules are formed by substrate-level ATP synthesis
Net gain of two ATP from glycolysis, why?
Both G3Ps are oxidized to pyruvates
Pyruvate enters mitochondria if oxygen is available and aerobic respiration follows
If oxygen is not available, glycolysis becomes a part of fermentation and pyruvate is reduced

15. Inputs and Outputs of Glycolysis

16. Glycolysis: Substrate-level ATP synthesis
A phosphate group is transferred to ADP giving one ATP molecule
During glycolysis, the C3 substrate BPG gives up a phosphate group to ADP
Occurs twice per glucose molecule

17. Glycolysis

18. Inside the Mitochondria
Aerobic Respiration – involves the preparatory reaction, the citric acid cycle and the electron transport system
Mitochondrion Structure and Function
Double membrane with an intermembrane space between the outer and inner membrane
Cristae - inner folds of membrane
Matrix - the innermost compartment filled with a gel-like fluid
Produces most of the ATP from cellular respiration (i.e. powerhouse of the cell)

19. Mitochondrion: Structure and Function

20. Glucose Breakdown: The Preparatory (Prep) Reaction
Preparatory reaction connects glycolysis to the citric acid cycle
End product of glycolysis (i.e. pyruvate) enters the mitochondrial matrix
Pyruvate is converted to a C2 acetyl group
Attached to CoA to form acetyl CoA
Electrons picked up by 2 NAD+ to give 2 NADH
CO2 is released and transported out of mitochondria into the cytoplasm
Reaction occurs twice per glucose molecule

21. Preparatory Reaction

22. Glucose Breakdown: Citric Acid Cycle
Also known as the Krebs cycle; a cyclic pathway occurring in the matrix of mitochondria
Both (C2) acetyl-CoA groups from the prep reaction:
Joins with a C4 molecule to give citrate (C6)
Each acetyl group is oxidized to two CO2 molecules
Electrons are accepted by NAD+ in three instances (forming 3 NADH) and by FAD in one instance (forming FADH2)
ATP is formed (per acetyl group) by substrate-level ATP synthesis

23. Citric Acid Cycle

24. Inputs and Outputs of The Citric Acid Cycle
Krebs cycle turns twice per glucose molecule

25. Electron Transport Chain (ETC)
Location:
Eukaryotes – cristae of the mitochondria
Aerobic Prokaryotes – plasma membrane
Series of carrier molecules:
Pass energy rich electrons along
Protein carriers such as cytochrome molecules
Cytochromes - proteins with a central iron (heme) group; the group is the one being oxidized & reduced
Receives electrons from NADH and FADH2 25

26. ETC (cont.) Oxygen is the final electron acceptor in the ETC
Lack of oxygen blocks the entire ETC – no additional ATP is produced leading to death
Some poisons also inhibit normal activity of cytochromes
Example: Cyanide binds to iron in cytochrome, blocking ATP production 26

27. Cycling of Carries The fate of the hydrogens:
H+ from NADH deliver enough energy to make 3 ATPs
Those from FADH2 have only enough for 2 ATPs
Recycling of coenzymes increases efficiency
Once NADH delivers H+, it returns (as NAD+) to pick up more H+
However, hydrogen atoms must be combined with oxygen to make water
If O2 is not present, NADH cannot release H+
No longer recycled back to NAD+ 27

28. ETC 28

29. Carriers on Cristae of a Mitochondrion
The ETC consists of 3 protein complexes and 2 carriers
The 3 protein complexes include:
NADH-Q reductase complex
Cytochrome reductase complex
Cytochrome oxidase complex
The other 2 carriers are coenzyme Q and cytochrome c
H+ carried by NADH and FADH2 are pumped by the protein complexes into the intermembrane space; thus creating H+ gradient 29

30. Organization and Function of Cristae30

31. ATP Production
ATP synthase complex – channel protein (in cristae) that serves as an enzyme for ATP synthesis
Protons diffuse from the intermembrane space (high conc.) to the matrix (low conc.) through the enzyme complex ATP synthase
This catalyzes the phosphorylation of ADP to form ATP – Chemiosmosis
ATP molecules them move out of the mitochondria to perform cellular work 31

32. Mitochondria in Active Tissue
ATP production must be constant in order to sustain life
Active tissues (e.g. muscles) require greater amounts of ATP and contain more mitochondria than less active cells
Example – Dark meat of chickens contains more mitochondria than the white meat of the breast 32

33. Energy Yield from Glucose Metabolism
Complete breakdown of glucose to CO2 and H2O yields 36 to 38 ATPs
Substrate-level ATP synthesis
2 ATP from glycolysis
2 AP from the citric acid cycle
Total of four ATP are formed outside of the electron transport system
32 to 34 ATP from the electron transport chain and chemiosmosis 33

34. Energy Yield from Glucose Metabolism (cont.)
ETC and Chemiosmosis
Per glucose molecule, 10 NADH and two FADH2 provide electrons and H+ ions to electron transport system
For each NADH formed within the mitochondrion, ATP are produced
For each FADH2 formed by Krebs cycle, 2 ATP result since FADH2 delivers electrons after NADH
For each NADH formed in the cytoplasm, 2 ATP are formed as electrons are “shuttled” across the mitochondrial membrane and delivered to FAD 34

35. Energy Yield from Glucose Breakdown
Total NADH = 8 x 3 ATP = 24 ATP
Total FADH2 = 2 x 2 ATP = 4 ATP
ETC yields 28 ATP
28 (ETC) + 4 (substrate level) = 32 ATP
Other 4 ATP comes from NADH produced by glycolysis which transport electrons via shuttle molecule to 2 FADH2, thus 2 x 2ATP = 4 ATP
Now we have = 36 ATP molecules 35

36. Efficiency of Cellular Respiration
Energy difference (∆G) = 686 kcal
One ATP phosphate bond has an energy content of 7.3 kcal
36 ATP produced during glucose breakdown (36 x 7.3) = 263 kcal
Efficiency is 263/686 x 100 = 39% of available energy from glucose
The rest of the energy is lost as heat 36

37. Overall Energy Yielded per Glucose Molecule

38. Fermentation When oxygen is limited: Fermentation:
Spent hydrogens have no final acceptor
NADH can’t recycle back to NAD+
Glycolysis stops because NAD+ is required
Fermentation:
“Anaerobic” pathway
Can provide rapid burst of ATP in the absence of O2
Provides NAD+ for glycolysis
NADH combines with pyruvate to yield NAD+
NAD+ is then free to return and pick up more e- during earlier reactions of glycolysis 38

39. Fermentation

40. Fermentation (cont.) Pyruvate is reduced by NADH to:
Lactate (Animals & anaerobic bacteria)
In muscles, pyruvate is reduced to lactate when it is produced faster than it can be oxidized by Krebs cycle
Cheese & yogurt
Industrial chemicals (i.e. isoprpanol, butyric acid, propionic acid & acetic acid)
Ethanol & carbon dioxide (Yeasts)
Bread & alcoholic beverages 40

41. Advantages and Disadvantages of Fermentation
Despite the low yield of 2 ATP, it provides a quick burst of energy for muscular activity
Allows glycolysis to proceed faster than O2 can be obtained
Anaerobic exercise
Lactic acid accumulates (toxic to cells)
Causes cramping and oxygen debt
When O2 restored, lactate is broken down to pyruvate; then respired or converted into glucose

42. Efficiency of Fermentation
Two ATP produced per glucose molecule during fermentation gives (2 x 7.3)= 14.6 kcal
Complete glucose breakdown to CO2 and H2O during cellular respiration = 686 kcal of energy
Efficiency is 14.6/686 x 100 = 2.1%
Much less efficient than complete breakdown of glucose

43. Catabolic and Anabolic Reactions
Metabolism – sum of all chemical reactions within a living organism
Catabolism – chemical reactions that result in the breakdown of complex organic compounds into simpler substances; thus releases energy
Example: Cellular Respiration
Anabolism – chemical reactions that build new molecules from simpler substances; thus requires energy
Example: Photosynthesis