1. How Cells make ATP: Energy-Releasing Pathways
Chapter 8
2nd edit BTT2 3/06 AD

2. Learning Objective 1
In aerobic respiration, which reactant is oxidized and which is reduced?

3. Aerobic Respiration A catabolic process Redox reactions
fuel (glucose) broken down to carbon dioxide and water
Redox reactions
transfer electrons from glucose (oxidized)
to oxygen (reduced)
Energy released
produces 36 to 38 ATP per glucose

4. KEY CONCEPTS
Aerobic respiration is an exergonic redox process in which glucose becomes oxidized, oxygen becomes reduced, and energy is captured to make ATP

5. Learning Objective 2
What are the four stages of aerobic respiration?

6. 4 Stages of Aerobic Respiration
Glycolysis
Formation of acetyl CoA
Citric acid cycle
Electron transport chain and chemiosmosis

7. Glycolysis 1 molecule of glucose degraded
to 2 molecules pyruvate
2 ATP molecules (net) produced
by substrate-level phosphorylation
4 hydrogen atoms removed
to produce 2 NADH

8. Glycolysis

9. Glycolysis Formation of acetyl coenzyme A Citric acid cycle
Electron transport
and
chemiosmosis
Glucose
Pyruvate
Figure 8.3: An overview of glycolysis.
The black spheres represent carbon atoms. The energy investment phase of glycolysis leads to the splitting of sugar; ATP and NADH are produced during the energy capture phase. During glycolysis, each glucose molecule is converted to two pyruvates, with a net yield of two ATP molecules and two NADH molecules.
2 ATP
2 ATP
32 ATP
Fig. 8-3, p. 175

10. Energy investment phase and splitting of glucose
GLYCOLYSIS
Energy investment phase and splitting of glucose
Two ATPs invested per glucose
Glucose
2 ATP 3
steps
2 ADP
Fructose-1,6-bisphosphate
Figure 8.3: An overview of glycolysis.
The black spheres represent carbon atoms. The energy investment phase of glycolysis leads to the splitting of sugar; ATP and NADH are produced during the energy capture phase. During glycolysis, each glucose molecule is converted to two pyruvates, with a net yield of two ATP molecules and two NADH molecules. P P
Glyceraldehyde
phosphate
(G3P)
Glyceraldehyde
phosphate
(G3P) P P
Fig. 8-3, p. 175

11. Energy capture phase Four ATPs and two NADH produced per glucose P P
(G3P)
(G3P)
NAD+
NAD+
NADH
NADH 5
steps
2 ADP
2 ADP
2 ATP
2 ATP
Figure 8.3: An overview of glycolysis.
The black spheres represent carbon atoms. The energy investment phase of glycolysis leads to the splitting of sugar; ATP and NADH are produced during the energy capture phase. During glycolysis, each glucose molecule is converted to two pyruvates, with a net yield of two ATP molecules and two NADH molecules.
Pyruvate
Pyruvate
Net yield per glucose:
Two ATPs and two NADH
Fig. 8-3, p. 175

12. Formation of Acetyl CoA
1 pyruvate molecule
loses 1 molecule of carbon dioxide
Acetyl group + coenzyme A
produce acetyl CoA
1 NADH produced per pyruvate

13. Formation of Acetyl CoA

14. Glycolysis Formation of acetyl coenzyme A Citric acid cycle
Electron transport
and
chemiosmosis
Glucose
Pyruvate
Figure 8.5: The formation of acetyl CoA.
This series of reactions is catalyzed by the multienzyme complex pyruvate dehydrogenase. Pyruvate, a three-carbon molecule that is the end product of glycolysis, enters the mitochondrion and undergoes oxidative decarboxylation. First, the carboxyl group is split off as carbon dioxide. Then, the remaining two-carbon fragment is oxidized, and its electrons are transferred to NAD+. Finally, the oxidized two-carbon group, an acetyl group, is attached to coenzyme A. CoA has a sulfur atom that forms a bond, shown as a black wavy line, with the acetyl group. When this bond is broken, the acetyl group can be readily transferred to another molecule.
2 ATP
2 ATP
32 ATP
Fig. 8-5, p. 178

15. Carbon CO2 dioxide Pyruvate NAD+ Coenzyme A NADH Acetyl coenzyme A
Figure 8.5: The formation of acetyl CoA.
This series of reactions is catalyzed by the multienzyme complex pyruvate dehydrogenase. Pyruvate, a three-carbon molecule that is the end product of glycolysis, enters the mitochondrion and undergoes oxidative decarboxylation. First, the carboxyl group is split off as carbon dioxide. Then, the remaining two-carbon fragment is oxidized, and its electrons are transferred to NAD+. Finally, the oxidized two-carbon group, an acetyl group, is attached to coenzyme A. CoA has a sulfur atom that forms a bond, shown as a black wavy line, with the acetyl group. When this bond is broken, the acetyl group can be readily transferred to another molecule.
Acetyl coenzyme A
Fig. 8-5, p. 178

16. Citric Acid Cycle 1 acetyl CoA enters cycle 2 C enter as acetyl CoA
combines with 4-C oxaloacetate
forms 6-C citrate
2 C enter as acetyl CoA
2 leave as CO2
1 acetyl CoA
transfers H atoms to 3 NAD+ , 1 FAD
1 ATP produced

17. Citric Acid Cycle

18. Glycolysis Formation of acetyl coenzyme A Citric acid cycle
Electron transport
and
chemiosmosis
Glucose
Pyruvate
Figure 8.6: Overview of the citric acid cycle.
For every glucose, two acetyl groups enter the citric acid cycle (top). Each two-carbon acetyl group combines with a four-carbon compound, oxaloacetate, to form the six-carbon compound citrate. Two CO2 molecules are removed, and energy is captured as one ATP, three NADH, and one FADH2 per acetyl group (or two ATPs, six NADH, and two FADH2 per glucose molecule).
2 ATP
2 ATP
32 ATP
Fig. 8-6, p. 179

19. Acetyl coenzyme A Coenzyme A Citrate Oxaloacetate NADH NAD+ NAD+
C I T R I C
A C I D
C Y C L E
H2O
NADH
CO2
FADH2
5-carbon compound
FAD
Figure 8.6: Overview of the citric acid cycle.
For every glucose, two acetyl groups enter the citric acid cycle (top). Each two-carbon acetyl group combines with a four-carbon compound, oxaloacetate, to form the six-carbon compound citrate. Two CO2 molecules are removed, and energy is captured as one ATP, three NADH, and one FADH2 per acetyl group (or two ATPs, six NADH, and two FADH2 per glucose molecule).
NADH
GTP
GDP
CO2
4-carbon compound
ADP
ATP
Fig. 8-6, p. 179

20. Electron Transport Chain
H atoms (or electrons) transfer
from one electron acceptor to another
in mitochondrial inner membrane
Electrons reduce molecular oxygen
forming water

21. Electron Transport Chain

22. Outer mitochondrial membrane
Cytosol
Outer mitochondrial membrane
Intermembrane space
Complex I: NADH–ubiquinone oxidoreductase
Complex IV: Cytochrome c oxidase
Complex III: Ubiquinone– cytochrome c oxidoreductase
Inner mitochondrial membrane
Complex II: Succinate– ubiquinone reductase
Figure 8.8: An overview of the electron transport chain.
Electrons fall to successively lower energy levels as they are passed along the four complexes of the electron transport chain located in the inner mitochondrial membrane. (The orange arrows indicate the pathway of electrons.) The carriers within each complex become alternately reduced and oxidized as they accept and donate electrons. The terminal acceptor is oxygen; one of the two atoms of an oxygen molecule (written as 1/2 O2) accepts 2 electrons, which are added to 2 protons from the surrounding medium to produce water.
Matrix of mitochondrion
FADH2
FAD
2 H+
H2O
NAD+
1/2 O2
NADH
Fig. 8-8, p. 181

23. Oxidative Phosphorylation
Redox reactions in ETC are coupled to ATP synthesis through chemiosmosis

24. KEY CONCEPTS
Aerobic respiration consists of four stages: glycolysis, formation of acetyl coenzyme A, the citric acid cycle, and the electron transport chain and chemiosmosis

25. Learning Objective 3
Where in a eukaryotic cell does each stage of aerobic respiration take place?

26. Aerobic Respiration Glycolysis occurs in the cytosol
All other stages in the mitochondria

27. Formation of acetyl coenzyme A Citric acid cycle 1 2 3 4
Glycolysis
Formation of acetyl coenzyme A
Citric acid cycle
Electron transport and chemiosmosis
Glucose
Mitochondrion
Acetyl coenzyme A
Citric acid cycle
Electron transport and chemiosmosis
Pyruvate
Figure 8.2: The four stages of aerobic respiration.
●1. Glycolysis, the first stage of aerobic respiration, occurs in the cytosol.
●2 Pyruvate, the product of glycolysis, enters a mitochondrion, where cellular respiration continues with the formation of acetyl CoA, ●3 the citric acid cycle, and ●4 electron transport and chemiosmosis. Most ATP is synthesized by chemiosmosis.
2 ATP
2 ATP
32 ATP
Fig. 8-2, p. 173

28. Learning Objective 4
Add up the energy captured (as ATP, NADH, and FADH2) in each stage of aerobic respiration

29. Energy Capture Glycolysis Conversion of 2 pyruvates to acetyl CoA
1 glucose: 2 NADH, 2 ATP (net)
Conversion of 2 pyruvates to acetyl CoA
2 NADH
Citric acid cycle
2 acetyl CoA: 6 NADH, 2 FADH2, 2 ATP
Total: 4 ATP, 10 NADH, 2 FADH2

30. Energy Transfer Electron transport chain (ETC)
10 NADH and 2 FADH2 produce 32 to 34 ATP by chemiosmosis
1 glucose molecule yields 36 to 38 ATP

31. Energy from Glucose

32. Substrate-level phosphorylation Oxidative phosphorylation Glycolysis
Glucose
Pyruvate
Acetyl coenzyme A
Citric acid cycle
Figure 8.11: Energy yield from the complete oxidation of glucose by aerobic respiration.
Total ATP from substrate-level phosphorylation
Total ATP from oxidative phosphorylation
Fig. 8-11, p. 185

33. Learning Objective 5 Define chemiosmosis
How is a gradient of protons established across the inner mitochondrial membrane?

34. Chemiosmosis Energy of electrons in ETC
pumps H+ across inner mitochondrial membrane
into intermembrane space
Protons (H+) accumulate in intermembrane space
lowering pH

35. Proton Gradient

36. Outer mitochondrial membrane Cytosol
Inner mitochondrial membrane
Figure 8.9: The accumulation of protons (H+) within the intermembrane space.
As electrons move down the electron transport chain, the electron transport complexes move protons (H+) from the matrix to the intermembrane space, creating a proton gradient. The high concentration of H+ in the intermembrane space lowers the pH.
Intermembrane space — low pH
Matrix — higher pH
Fig. 8-9, p. 183

37. Learning Objective 6
How does the proton gradient drive ATP synthesis in chemiosmosis?

38. ATP Synthase Enzyme ATP synthase
forms channels through inner mitochondrial membrane
Diffusion of protons through channels provides energy to synthesize ATP

39. ETC and Chemiosmosis

40. Cytosol Outer mitochondrial membrane Intermembrane space Complex V:
ATP
synthase
Complex
III
Complex IV
Inner
mitochondrial
membrane
Complex I
Complex II
Matrix of
mitochondrion
FADH2
Figure 8.10: A detailed look at electron transport and chemiosmosis.
NAD+ 1 2
NADH
ADP Pi
ATP
Fig. 8-10a, p. 184

41. Projections of ATP synthase
Figure 8.10: A detailed look at electron transport and chemiosmosis.
250 nm
(b) This TEM shows hundreds of projections of ATP synthase complexes along the surface of the inner mitochondrial membrane.
Fig. 8-10b, p. 184

42. Learning Objective 7
How do the products of protein and lipid catabolism enter the same metabolic pathway that oxidizes glucose?

43. Amino Acids Undergo deamination Carbon skeletons converted
to intermediates of aerobic respiration

44. Lipids Glycerol and fatty acids Fatty acids both oxidized as fuel
converted to acetyl CoA by β-oxidation

45. Catabolic Pathways

46. Electron transport and chemiosmosis
PROTEINS
CARBOHYDRATES
FATS
Amino acids
Glycolysis
Glycerol
Fatty acids
Glucose
G3P
Pyruvate
CO2
Acetyl coenzyme A
Citric acid cycle
Figure 8.12: Energy from proteins, carbohydrates, and fats.
Products of the catabolism of proteins, carbohydrates, and fats enter glycolysis or the citric acid cycle at various points. This diagram is greatly simplified and illustrates only a few of the principal catabolic pathways.
Electron transport and chemiosmosis
End products:
NH3
H2O
CO2
Fig. 8-12, p. 186

47. PROTEINS Amino acids CARBOHYDRATES Glucose Glycolysis G3P Pyruvate
FATS
Glycerol
Fatty acids
CO2
Acetyl coenzyme A
NH3
Citric acid cycle
CO2
Fig 8-12
Electron
transport and
chemiosmosis
H2O
Stepped Art
End products:
Fig. 8-12, p. 186

48. KEY CONCEPTS
Nutrients other than glucose, including many carbohydrates, lipids, and amino acids, can be oxidized by aerobic respiration

49. Learning Objective 8
Compare the mechanism of ATP formation, final electron acceptor, and end products of anaerobic respiration and fermentation

50. Anaerobic Respiration
Electrons transferred
from fuel molecules to ETC
coupled to ATP synthesis (chemiosmosis)
Final electron acceptor
inorganic substance
nitrate or sulfate (not molecular oxygen)

51. KEY CONCEPTS
In anaerobic respiration carried out by some bacteria, ATP is formed during a redox process in which glucose becomes oxidized and an inorganic substance becomes reduced

52. Fermentation Anaerobic process Net energy gain only 2 ATP per glucose
no ETC
Net energy gain only 2 ATP per glucose
produced by substrate-level phosphorylation during glycolysis
NAD+
produced by transferring H from NADH to organic compound from nutrient

53. Fermentation Alcohol fermentation Lactate (lactic acid) fermentation
in yeast cells
waste products: ethyl alcohol, CO2
Lactate (lactic acid) fermentation
some fungi, prokaryotes, animal cells
H atoms added to pyruvate
waste product: lactate

54. KEY CONCEPTS
Fermentation is an inefficient anaerobic redox process in which glucose becomes oxidized and an organic substance becomes reduced
Some fungi and bacteria, as well as muscle cells under conditions of low oxygen, obtain low yields of ATP through fermentation

55. Fermentation

56. Fig. 8-13, p. 187 Figure 8.13: Fermentation.
(a) Light micrograph of live brewer’s yeast (Saccharomyces cerevisiae). Yeast cells have mitochondria and carry on aerobic respiration when O2 is present. In the absence of O2, yeasts carry on alcohol fermentation. (b, c) Glycolysis is the first part of fermentation pathways. In alcohol fermentation (b), CO2 is split off, and the two-carbon compound ethyl alcohol is the end product. In lactate fermentation (c), the final product is the three-carbon compound lactate. In both alcohol and lactate fermentation, there is a net gain of only two ATPs per molecule of glucose. Note that the NAD used during glycolysis is regenerated during both alcohol fermentation and lactate fermentation.
Fig. 8-13, p. 187

57. 25 μm Fig. 8-13a, p. 187 Figure 8.13: Fermentation.
(a) Light micrograph of live brewer’s yeast (Saccharomyces cerevisiae). Yeast cells have mitochondria and carry on aerobic respiration when O2 is present. In the absence of O2, yeasts carry on alcohol fermentation.
25 μm
Fig. 8-13a, p. 187

58. (b) Alcohol fermentation
Glycolysis
Glucose
2 NAD+
2 NADH
2 ATP
2 Pyruvate
Figure 8.13: Fermentation.
(b, c) Glycolysis is the first part of fermentation pathways. In alcohol fermentation (b), CO2 is split off, and the two-carbon compound ethyl alcohol is the end product.
CO2
2 Ethyl alcohol
(b) Alcohol fermentation
Fig. 8-13b, p. 187

59. (c) Lactate fermentation
Glycolysis
Glucose
2 NAD+
2 NADH
2 ATP
2 Pyruvate
Figure 8.13: Fermentation.
(b, c) Glycolysis is the first part of fermentation pathways. In alcohol fermentation (b), CO2 is split off, and the two-carbon compound ethyl alcohol is the end product. In lactate fermentation (c), the final product is the three-carbon compound lactate. In both alcohol and lactate fermentation, there is a net gain of only two ATPs per molecule of glucose. Note that the NAD used during glycolysis is regenerated during both alcohol fermentation and lactate fermentation.
2 Lactate
(c) Lactate fermentation
Fig. 8-13c, p. 187

60. Summary Reaction Complete oxidation of glucose
C6H12O6 + 6 O H2O →
6 CO H2O + energy (36 to 38 ATP)

61. → 2 pyruvate + 4 ATP + 2 NADH + H2O
Summary Reaction
Glycolysis
C6H12O6 + 2 ATP + 2 ADP + 2 Pi + 2 NAD+
→ 2 pyruvate + 4 ATP + 2 NADH + H2O

62. Glycolysis in Detail

63. Energy investment phase and splitting of glucose
Two ATPs invested per glucose
Glucose 1
Glycolysis begins with preparation reaction in which glucose receives phosphate group from ATP molecule. ATP serves as source of both phosphate and energy needed to attach phosphate to glucose molecule. (Once ATP is spent, it becomes ADP and joins ADP
pool of cell until turned into ATP again.) Phosphorylated glucose is known as glucose-6-phosphate. (Note phosphate attached to its carbon atom 6.) Phosphorylation of glucose makes it more chemically reactive.
ATP
Hexokinase
ADP
Figure 8.4: A detailed look at glycolysis.
A specific enzyme catalyzes each of the reactions in glycolysis. Note the net yield of two ATP molecules and two NADH molecules. (The black wavy lines indicate bonds that permit the phosphates to be readily transferred to other molecules; in this case, ADP.)
Glucose-6-phosphate
Phosphoglucoisomerase
Fig. 8-4a, p. 176

64. Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate (G3P)2
Glucose-6-phosphate undergoes another preparation reaction, rearrangement of its hydrogen and oxygen atoms. In this reaction glucose-6-phosphate is converted to its isomer, fructose-6-phosphate.
Fructose-6-phosphate
ATP
Phosphofructokinase
ADP 3
Next, another ATP donates phosphate to molecule, forming fructose-1,6-bisphosphate. So far, two ATP molecules have been invested in process without any being produced. Phosphate groups are now bound at carbons 1 and 6, and molecule is ready to be split.
Fructose-1,6-bisphosphate
Aldolase
Figure 8.4: A detailed look at glycolysis.
A specific enzyme catalyzes each of the reactions in glycolysis. Note the net yield of two ATP molecules and two NADH molecules. (The black wavy lines indicate bonds that permit the phosphates to be readily transferred to other molecules; in this case, ADP.) 4
Fructose-1,6-bisphosphate is then split into two 3-carbon sugars, glyceraldehyde-3- phosphate (G3P) and dihydroxyacetone phosphate.
Dihydroxyacetone phosphate is enzymatically converted to its isomer, glyceraldehyde-3- phosphate, for further metabolism in glycolysis.
Isomerase 5
Dihydroxyacetone
phosphate
Glyceraldehyde-
3-phosphate (G3P)
Fig. 8-4a, p. 176

65. Two glyceraldehyde-3-phosphate (G3P) from bottom of previous page
Energy capture phase
Four ATPs and two NADH produced per glucose
2 NAD+
Glyceraldehyde-3-phosphate dehydrogenase
2 NADH 6
Each glyceraldehyde-3-phosphate undergoes dehydrogenation
with NAD+ as hydrogen acceptor. Product
of this very exergonic reaction is phosphoglycerate,
which reacts with inorganic phosphate present in
cytosol to yield 1,3-bisphosphoglycerate.
Two 1,3-bisphosphoglycerate
2 ADP
Phosphoglycerokinase
2 ATP
Figure 8.4: A detailed look at glycolysis.
A specific enzyme catalyzes each of the reactions in glycolysis. Note the net yield of two ATP molecules and two NADH molecules. (The black wavy lines indicate bonds that permit the phosphates to be readily transferred to other molecules; in this case, ADP.) 7
One of phosphates of 1,3-bisphosphoglycerate reacts
with ADP to form ATP. This transfer of phosphate from
phosphorylated intermediate to ATP is referred to as
substrate-level phosphorylation.
Two 3-phosphoglycerate
Phosphoglyceromutase
Fig. 8-4b, p. 177

66. Two phosphoenolpyruvate8
3-phosphoglycerate is rearranged to 2-phosphoglycerate
by enzymatic shift of position of phosphate group.
This is a preparation reaction.
Two 2-phosphoglycerate
Enolase
2 H2O 9
Next, molecule of water is removed, which results in
formation of double bond. The product, phosphoenolpyruvate (PEP), has phosphate group attached by an unstable bond (wavy line).
Two phosphoenolpyruvate
2 ADP
Pyruvate kinase
2 ATP
Figure 8.4: A detailed look at glycolysis.
A specific enzyme catalyzes each of the reactions in glycolysis. Note the net yield of two ATP molecules and two NADH molecules. (The black wavy lines indicate bonds that permit the phosphates to be readily transferred to other molecules; in this case, ADP.) 10
Each of two PEP molecules transfers its phosphate group
to ADP to yield ATP and pyruvate. This is substrate-level
phosphorylation reaction.
Two pyruvate
Fig. 8-4b, p. 177

67. 2 pyruvate + 2 coenzyme A + 2 NAD+ →
Summary Reaction
Conversion of pyruvate to acetyl CoA
2 pyruvate + 2 coenzyme A + 2 NAD+ →
2 acetyl CoA + 2 CO2 + 2 NADH

68. 2 acetyl CoA + 6 NAD+ + 2 FAD + 2 ADP
Summary Reaction
Citric acid cycle
2 acetyl CoA + 6 NAD+ + 2 FAD + 2 ADP
+ 2 Pi + 2 H2O → 4 CO2 + 6 NADH +
2 FADH2 + 2 ATP + 2 CoA

69. Citric Acid Cycle in Detail

70. Summary Reactions Hydrogen atoms in ETC
NADH + 3 ADP + 3 Pi O2 → NAD+ + 3 ATP + H2O
FADH2 + 2 ADP + 2 Pi + 12 O2 → FAD ATP + H2O

71. Summary Reaction Lactate fermentation
C6H12O6 → 2 lactate + energy (2 ATP)

72. C6H12O6 → 2 CO2 + 2 ethyl alcohol + energy (2 ATP)
Summary Reaction
Alcohol fermentation
C6H12O6 → 2 CO2 + 2 ethyl alcohol + energy (2 ATP)

73. The Overall Reactions of Glycolysis
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