1. How Cells Release Chemical Energy
Chapter 8

2. Cellular or Aerobic Respiration
Cellular respiration evolved to enable organisms to utilize energy stored in glucose.
Taps the energy found in the bonds of organic compounds (carbohydrates, lipids, proteins)

3. Comparison of the Main Pathways
Aerobic respiration
Aerobic metabolic pathways (using oxygen) are used by most eukaryotic cells
Ends in the mitochondria
Aerobes use oxygen as the final electron acceptor
Fermentation
Anaerobic metabolic pathways (occur in the absence of oxygen) are used by prokaryotes and protists in anaerobic habitats
Anaerobes use nitrate or sulfate as the final e- acceptor

4. Comparison of the Main Pathways
Aerobic respiration and fermentation both begin with glycolysis, which converts one molecule of glucose into two molecules of pyruvate
After glycolysis, the two pathways diverge
Fermentation is completed in the cytoplasm, yielding 2 ATP per glucose molecule
Aerobic respiration is completed in mitochondria, yielding 36 ATP per glucose molecule (liberates the most energy)

5. Overview of Aerobic Respiration
Three sequential stages
Glycolysis
Acetyl-CoA formation and Krebs cycle
Electron transfer phosphorylation (ATP formation)
C6H12O6 (glucose) + O2 (oxygen) →
CO2 (carbon dioxide) + H2O (water)
Coenzymes NADH and FADH2

6. Figure 8.3
Overview of aerobic respiration. The reactions start in the cytoplasm and end inside mitochondria. The pathway’s inputs and outputs are summarized on the right.
Figure It Out: What is aerobic respiration’s net yield of ATP?
Answer: 38 – 2 = 36 ATP per glucose
Fig. 8-3b, p. 125

7. Animation: Overview of aerobic respiration

8. 8.2 Glycolysis – Glucose Breakdown Starts
Glycolysis starts and ends in the cytoplasm of all prokaryotic and eukaryotic cells
An energy investment/input of ATP (2) starts glycolysis
Requires a continous supply of glucose and NAD+ (reduced in both glycolysis and the kreb cycle)

9. Glycolysis
Two ATP’s are used to split glucose (6 carbon compound) and form 2 PGAL (3 carbon compound)
Enzymes convert 2 PGAL to 2 PGA, forming 2 NADH
Four ATP are formed by substrate-level phosphorylation (net yield of 2 ATP)

10. Figure 8.4
Glycolysis. This first stage of carbohydrate breakdown starts and ends in the cytoplasm of prokaryotic and eukaryotic cells. Glucose (right) is the reactant in the example shown on the opposite page; we track its six carbon atoms (black balls). Appendix VI shows the complete structures of the intermediates and the products.
Fig. 8-4a (2), p. 126

11. fructose-1,6-bisphosphate (intermediate)
ATP-Requiring Steps
Glycolysis
A An enzyme transfers a phosphate group from ATP to glucose, forming glucose-6-phosphate.
glucose
ATP
ADP
B A phosphate group from a second ATP is transferred to the glucose-
6- phosphate. The resulting molecule is unstable, and it splits into two three- carbon molecules. The molecules are interconvertible, so we will call them both PGAL
(phosphoglyceraldehyde).
glucose-6-phosphate
ATP
ADP
Figure 8.4
Glycolysis. This first stage of carbohydrate breakdown starts and ends in the cytoplasm of prokaryotic and eukaryotic cells. Glucose (right) is the reactant in the example shown on the opposite page; we track its six carbon atoms (black balls). Appendix VI shows the complete structures of the intermediates and the products.
fructose-1,6-bisphosphate (intermediate)
So far, two ATP have been invested in the reactions.
Fig. 8-4b (1), p. 127

12. The original energy investment of two ATP has now been recovered.
ATP-Generating Steps
C Enzymes attach a phosphate to the two PGAL, and transfer two electrons and a hydrogen ion from each PGAL to NAD+. Two PGA (phosphoglycerate) and two NADH are the result.
2 PGAL
2 NAD+ + 2 Pi
NADH
2 reduced coenzymes
D Enzymes transfer a phosphate group from each PGA to ADP. Thus, two ATP have formed by substrate-level phosphorylation.
2 PGA
2 ADP
ATP
The original energy investment of two ATP has now been recovered.
2 ATP produced
by substrate-level phosphorylation
E Enzymes transfer a phosphate group from each of two intermediates to ADP. Two more ATP have formed by substrate-level phosphorylation.
2 PEP
2 ADP
Figure 8.4
Glycolysis. This first stage of carbohydrate breakdown starts and ends in the cytoplasm of prokaryotic and eukaryotic cells. Glucose (right) is the reactant in the example shown on the opposite page; we track its six carbon atoms (black balls). Appendix VI shows the complete structures of the intermediates and the products.
ATP
2 ATP produced
by substrate-level phosphorylation
Two molecules of pyruvate form at this last reaction step.
2 pyruvate
F Summing up, glycolysis yields two NADH, two ATP (net), and two pyruvate for each glucose molecule.
Net 2 ATP + 2 NADH
to second stage
Fig. 8-4b (2), p. 127

13. 8.3 Second Stage of Aerobic Respiration
The second stage of aerobic respiration finishes breakdown of glucose that began in glycolysis
Occurs in mitochondria (inner compartment) begans with the chemical pyruvate to continue respiration
Includes two stages: acetyl CoA formation and the Krebs cycle (each occurs twice in the breakdown of one glucose molecule)

14. The Krebs Cycle Krebs cycle
A sequence of enzyme-mediated reactions that break down 1 acetyl CoA (transition stage) into 2 CO2
Oxaloacetate (last intermediate) is used and regenerated
3 NADH and 1 FADH2 are formed, 1 ATP is formed
Substrate level phosphorylation occurs
Electrons and hydrogens are transferred to coenzymes in both glycolysis and the Kreb cycle
Energy, CO2, and H+ are released
Cycle turns 2x to break down glucose

15. Acetyl–CoA Formation transition from glyco
A An enzyme splits a pyruvate molecule into a two-carbon acetyl group and CO2. Coenzyme A binds the acetyl group (forming acetyl–CoA). NAD+ combines with released hydrogen ions and electrons, forming NADH.
NADH
pyruvate
CO2
NAD+
coenzyme A
acetyl–CoA
B The Krebs cycle starts as one carbon atom is transferred from acetyl–CoA to oxaloacetate. Citrate forms, and coenzyme A is regenerated.
oxaloacetate
coenzyme A
citrate
Krebs
Cycle
H The final steps of the Krebs cycle regenerate oxaloacetate.
NADH
G NAD+ combines with hydrogen ions and electrons, forming NADH.
NAD+
C A carbon atom is removed from an intermediate and leaves the cell as CO2. NAD+ combines with released hydrogen ions and electrons, forming NADH.
NADH
CO2
NAD+
Figure 8.6
Aerobic respiration’s second stage: acetyl–CoA formation and the Krebs cycle. One set of second-stage reactions converts one pyruvate to three CO2 for a yield of one ATP, four NADH, and one FADH2 (right). The reactions occur in the mitochondrion’s inner compartment. For simplicity, many of the pathway’s intermediates are not shown. See Appendix VI for the detailed reactions.
FADH2
F The coenzyme FAD com-bines with hydrogen ions and electrons, forming FADH2.
FAD
Pyruvate’s three carbon atoms have now exited the cell, in CO2.
D A carbon atom is removed from another intermediate and leaves the cell as CO2, and another NADH forms.
NADH
CO2
NAD+
ATP
E One ATP forms by substrate-level phosphorylation.
ADP + Pi
Stepped Art
Fig. 8-6, p. 129

16. Animation: The Krebs Cycle - details

17. 8.4 Aerobic Respiration’s Big Energy Payoff
Many ATP’s are formed during the third and final stage of aerobic respiration (Chemiosmotic Theory = production of ATP’s)
Electron transfer phosphorylation
Occurs in mitochondria (inner membrane)
Results in attachment of phosphate to ADP to form ATP
Generates a hydrogen concentration (build up of hydrogen ions between 2 membranes) gradient

18. Electron Transfer Phosphorylation

19. Summary: The Energy Harvest
Typically, the breakdown of one glucose molecule yields 36 ATP
Glycolysis: 2 ATP
Acetyl CoA formation and Krebs cycle: 2 ATP
Electron transfer phosphorylation: 32 ATP

20. Animation: Third-stage reactions

21. 8.5 Anaerobic Energy-Releasing Pathways
Fermentation pathways break down carbohydrates without using oxygen (Ex. Bacteria that causes botulism)
The final steps in these pathways regenerate NAD+

22. Fermentation Pathways
Glycolysis is the first stage of fermentation
Forms 2 pyruvate, 2 NADH, and 2 ATP
Pyruvate turns to lactic acid using e- from NADH (Lactate/Lactose Fermentation)
Pyruvate is converted to ethanol producing acetaldehyde and CO2 (Alcoholic Fermentation)

23. Two Pathways of Fermentation
Alcoholic fermentation
Pyruvate produce acetaldehyde and CO2 when converted to ethanol
Acetaldehyde receives electrons and hydrogen from NADH, forming NAD+ and ethanol
Lactate fermentation
Pyruvate receives electrons and hydrogen from NADH, forming NAD+ and lactate (muscle cells, sour cream, etc)

24. Alcoholic Fermentation 2 CO2
Glycolysis
glucose
2 NAD+ 2
ATP
NADH 4
pyruvate
glucose
Glycolysis
2 NAD+ 2
ATP
NADH
pyruvate 4 2
NADH
2 NAD+
ethanol 2
NADH
2 NAD+
Alcoholic Fermentation
2 CO2
acetaldehyde
Lactate Fermentation
lactate
Figure 8.9
(a) Alcoholic fermentation. (b) Lactate fermentation. In both pathways, the final steps do not produce ATP. They regenerate NAD+. The net yield is two ATP per molecule of glucose (from glycolysis).
Stepped Art
Fig. 8-9, p. 132

25. 8.6 The Twitchers
Slow-twitch muscle fibers (“red” muscles) make ATP by aerobic respiration
Have many mitochondria
Dominate in prolonged activity
Fast-twitch muscle fibers (“white” muscles) make ATP by lactate fermentation
Have few mitochondria and no myoglobin
Sustain short bursts of activity
Human muscles have a mixture of both fibers

26. 8.7 Alternative Energy Sources in the Body
In humans and other mammals, the entrance of glucose and other organic compounds into an energy-releasing pathway depends on the kinds and proportions of carbohydrates (our main source of energy), fats and proteins in the diet

27. The Fate of Glucose at Mealtime and Between Meals
When blood glucose concentration rises, the pancreas increases insulin (hormone) secretion
Cells take up glucose faster, more ATP is formed
When blood glucose concentration falls, the pancreas increases glucagon (hormone) secretion (between meals)
Stored glycogen is converted to glucose, the brain continues to receive glucose
Triglycerides are tapped as an energy alternative.

28. Energy From Fats
About 78% of an adult’s energy reserves is stored in fat (mostly triglycerides)
Excess glucose(carbs) in the diet = FAT; acetyl Co A exits the Kreb Cycle and enters a pathway that makes fatty acids
Enzymes cleave fats into glycerol and fatty acids
Glycerol products enter glycolysis
Fatty acid products enter the Krebs cycle

29. Energy from Proteins
Enzymes split dietary proteins into amino acid subunits, which enter the bloodstream
Used to build proteins or other molecules
Excess amino acids are broken down into ammonia (NH3) and various products that can enter the Krebs cycle

30. Electron Transfer Phosphorylation
FOOD
FATS
COMPLEX CARBOHYDRATES
PROTEINS
fatty acids
glycerol
glucose, other simple sugars
amino acids
acetyl–CoA
PGAL
acetyl–CoA
Glycolysis
NADH
pyruvate
oxaloacetate or another intermediate of the Krebs
Figure 8.12
Reaction sites where a variety of organic compounds enter aerobic respiration. Such compounds are alternative energy sources in the human body.
In humans and other mammals, complex carbohydrates, fats, and proteins from food do not enter the pathway of aerobic respiration directly. First, the digestive system, and then individual cells, break apart all of these molecules into simpler subunits. We return to this topic in Chapter 40.
Krebs Cycle
NADH, FADH2
Electron Transfer Phosphorylation
Fig. 8-12, p. 135