1. Chapter 25: Metabolism

2. Introduction to Cellular Metabolism
Formation of
Organic
Molecules
Energy production
begins in cytosol
Energy is
captured to
produce ATP
Figure 25–1

3. Energy Large food molecules contain energy
Energy in the form of chemical bonds
Work required to liberate energy
ATP: breaking the P bond provides
energy for cells
ATP ADP + P + free energy from food
Food Energy + ADP + P  ATP
(This ATP permits anabolism)

4. Energy Cells break down organic molecules to obtain energy:
used to generate ATP
Most energy production takes place in mitochondria

5. Essential Materials Oxygen Water
absorbed at the lungs
Water
Nutrients: absorbed at digestive tract
vitamins
mineral ions
organic substrates

6. Materials Transport Cardiovascular system: Materials diffuse:
carries materials through body
Materials diffuse:
from bloodstream into cells

7. Metabolism Refers to all chemical reactions in an organism
Includes all chemical reactions within cells
Provides energy to maintain homeostasis and perform essential functions

8. Essential Metabolic Functions
Metabolic turnover:
periodic replacement of cell’s organic components
Growth and cell division
Special processes:
secretion
contraction
propagation of action potentials

9. The Nutrient Pool Contains all organic building blocks cell needs:
to provide energy
to create new cellular components
Is source of substrates for catabolism and anabolism
Catabolism:
Is the breakdown of organic substrates
Releases energy used to synthesize high-energy compounds (e.g., ATP)
Anabolism:
Is the synthesis of new organic molecules via forming new chemical bonds

10. Nutrient Use in Cellular Metabolism
Figure 25–2 (Navigator)

11. Organic Compounds Glycogen (carbohydrates) short carbon chains
most abundant storage carbohydrate
a branched chain of glucose molecules
Triglycerides fatty acids and glycerol
most abundant storage lipids
primarily of fatty acids
Proteins amino acids
most abundant organic components in body
perform many vital cellular functions

12. KEY CONCEPT There is an energy cost to staying alive
Even at rest cells must spend ATP to:
perform routine maintenance
remove and replace structures and components
Cells spend additional energy for vital functions:
growth
secretion
contraction

13. Oxidation-Reduction Reactions (Redox Rxns)
Oxidation = the removal of electrons (Or addition of oxygen)
Reduction = the addition of electrons
These reactions are always coupled
One molecule must be oxidized while another is reduced
A-e’ + B  A + B-e’
Oxidized molecule (A): Loses energy OIL
Reduced molecule (B): Gains energy RIG

14. Oxidation-Reduction Reactions (Redox Rxns)
Cells perform dehydrogenation reactions
Hydrogen (1 proton + 1 electron) is exchanged instead of a free electron, but this is still a redox reaction
Catabolism of large molecules result in reduced carrier compounds
e.i. ADP  ATP; NAD  NADH; FAD  FADH2
These reduced compounds are later oxidized to generate ATP

15. ATP Production Requires the addition of a phosphate to ADP
Two Methods for ATP Productions
Substrate Level Phosphorylation
- High energy phosphate is transferred directly from a substrate to ADP forming ATP
Oxidative Phosphorylation
Electrons are transferred from an organic compound to a cofactor carrier molecule (e.g. NAD+)
Electrons are passed through other carriers (the electron transport chain) to a final acceptor (oxygen)
The passing of electrons releases energy that is harvested to add a phosphate to ADP
Process is called chemiosmosis.

16. What are the basic steps in glycolysis, the TCA cycle, and the electron transport system?

17. Carbohydrate Catabolism (Metabolism)
Carbohydrates are the primary source of cellular energy for most organisms
Glucose is the most commonly used carbohydrate and will always be used first
Generates ATP and other high-energy compounds by breaking down carbohydrates:
glucose + oxygen  carbon dioxide + water 

18. Carbohydrate Catabolism (Metabolism)
Two methods for ATP productions via catabolism of glucose
Cellular Respiration
Requires oxygen to serve as the final electron acceptor in a series of redox reactions
Generate ATP by oxidative phosphorylation
Most efficient method of ATP production
1 glucose generates 36 ATP
Involves reaction performed inside the mitochondria

19. Carbohydrate Catabolism (Metabolism)
Two methods for ATP productions via catabolism of glucose
2. Fermentation
Requires an organic molecule to serve as the final electron acceptor
Can be done in the absence of oxygen
ATP is synthesized using substrate level phosphorylation
Less efficient, 1 glucose generates 2 ATP
In humans, results in lactic acid

20. Anaerobic Vs. Aerobic Respiration Glycolysis
Anaerobic reactions: Fermentation
Do not require oxygen
Example: Glycolysis
Breaks down glucose in cytosol:
into smaller molecules used by mitochondria
Aerobic reactions: Cellular Respiration
Occur in mitochondria:
consume oxygen
produce ATP

21. Aerobic Respiration of Glucose C6H12O6 + 6O2  6 CO2 + 6H2O
Three Stages
Glycolysis
Oxidation of glucose to pyruvic acid
Some ATP and NADH produced
Citric Acid Cycle
Oxidation of acetyl to carbon dioxide
Some ATP, NADH and FADH produced
Electron Transport Chain
NADH and FADH2 are oxidized providing electrons for redox reactions
coenzymes that function to transport electrons in the form of hydrogen
Reduce oxygen to generate ATP
Majority of ATP is produced at this step

22. Nutrient Use in Cellular Metabolism
Figure 25–2 (Navigator)

23. Glycolysis (Anaerobic Process)
Does not require oxygen
Occurs in cytoplasm
10 step metabolic pathway:
Catabolizes and oxidizes one 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules
Generates 2 ATP by substrate level phosphorylation
Many cells can survive on glycolysis alone
Not very efficient
Generates lactic acid as a waste product
Needs to be removed and processed to prevent
Drastic alterations in pH
Loss of homeostasis

24. Glycolysis Factors Glucose molecules Cytoplasmic enzymes ATP and ADP
Inorganic phosphates
NAD (coenzyme)

26. Two Stages in Glycolysis
Preparatory Stage:
Enzyme phosphorylates last (sixth) carbon atom of glucose molecule:
Glucose-6-phosphate is formed using 1 ATP molecule
- traps glucose molecule within cell
Fructose 1,6-bisphosphate is formed using 1 ATP
Therefore, two ATP molecules are used to phosphorylate one 6-carbon glucose and catabolize it into two 3-carbon molecules

27. Two Stages in Glycolysis
Energy Conservation Stage:
the two 3-carbon molecules are oxidized to generate two 3-carbon pyruvic acid molecules
Two NAD+ molecules are reduced to two NADH molecules
4 ATP molecules are produced by substrate level phosphorylation
net gain 2 ATP per 1 glucose

28. Summary of Glycolysis 1 glucose + 2 NAD+ + 2 ADP + 2P 
2 pyruvic acid + 2 NADH + 2H+ + 2 ATP

29. Aerobic Reactions If oxygen supplies are adequate:
mitochondria absorb and break down pyruvic acid molecules

30. Mitochondrial Membranes
Outer membrane:
contains large-diameter pores
permeable to ions and small organic molecules (pyruvic acid)
Inner membrane:
contains carrier protein
moves pyruvic acid into mitochondrial matrix
Intermembrane space:
separates outer and inner membranes

31. Mitochondrial ATP Production
H atoms of pyruvic acid:
are removed by coenzymes
are primary source of energy gain
C and O atoms:
are removed and released as CO2
process of decarboxylation

32. The TCA Cycle
PLAY
TCA Cycle
Figure 25–4a (Navigator)

33. Decarboxylation Preparation of the Citric Acid Cycle
First step in aerobic process of glucose metabolism (oxygen is necessary)
3 carbon pyruvic acid is decarboxylated into carbon dioxide and a 2 carbon acetyl
Acetyl is attached to coenzyme A (serves as a carrier) and one NAD+ is reduced to NADH
Occurs in the matrix of the mitochondria

34. Summary of Decarboxylation
2 pyruvic acid + 2 NAD+ + 2 CoA 
2 Acetyl CoA + 2 CO2 + 2 NADH

35. Citric Acid Cycle a.k.a. Kreb’s Cycle or Tricarboxylic Acid Cycle
Aerobic metabolism of glucose involves
8 enzymatic reactions occurring in the mitochondrial matrix
Function to reduce the coenzyme NAD+ and FAD
2-carbon acetyl + 4-carbon and 2 CO2 molecules
At the same time oxaloacetic acid 
6-carbon citric acid
Oxidation and decarboxylation reactions:
Catabolize the 6-carbon citric acid back into a 4-carbon oxaloacetic acid
3 NAD+ and 1 FAD are reduced into 3 NADH and 1 FADH2
1 ATP is produced by substrate level phosphorylation

36. The TCA Cycle
Figure 25–4b

37. Citric Acid Cycle Remember: 2Acetyl Co A + 6NAD+ + 2FAD + 2ADP +
1 glucose  2 pyruvic acid 
2 acetyl so this cycle will run twice
2Acetyl Co A + 6NAD+ + 2FAD + 2ADP +
2P + 4H20 
2CoA + 4CO2 + 6NADH + 4H+ +
2FADH2 + 2ATP

38. Oxidative Phosphorylation
Figure 25–5a (Navigator)

39. Oxidative Phosphorylation
Occurs on a membrane, the mitochondrial cristae,
to generate most of the ATP produced from glucose
Figure 25–5b

40. Oxidative Phosphorylation
Is the most important mechanism for generation of ATP within the mitochondria
Produces more than 90% of ATP used by body
Requires oxygen, electrons, and coenzymes:
rate of ATP generation is limited by oxygen or electrons
Cells obtain oxygen by diffusion from extracellular fluid
Results in 2 H2 + O2 2 H2O

41. The Electron Transport System (ETS)
Key reaction in oxidative phosphorylation
Is in inner mitochondrial membrane
Coenzymes from the previous reactions pass electrons (which transfer energy) to a series of electron carrier molecules
Molecules carry out redox reactions resulting in the chemiosmotic generation of ATP

42. The Electron Transport System (ETS)
Three classes of carrier molecules
FMN (flavin mononucleotide): protein + flavin coenzyme
Coenzyme Q: nonprotein
Cytochromes: protein + an iron group
- Most common

43. Events of the Electron Transport Chain
NAD+ and FAD collected energy in the form of hydrogens (electrons) from organic molecules during Glycolysis, Decarboxylation, and the Citric Acid Cycle becoming that reduced forms NADH and FADH2
NAD+ + FAD  NADH + FADH2
NADH and FADH2 are oxidized and pass hydrogens (electrons and protons) to the electron transport chain consisting of flavoproteins, cytochromes, and coenzyme Q.
NADH + FADH2  NAD+ + FAD
As electrons are passed along the chain, protons are pushed out through the membrane. This sets up a concentration gradient with protons (+ charge) on the outside and electrons (- charge) on the inside

44. Events of the Electron Transport Chain
At the end of the chain the electrons are accepted by oxygen creating an anion (O-) inside, which has a strong affinity for the cations (H+) outside.
Chemiosmosis generates ATP:
- H+ from the outside moves toward O- on the inside through
special membrane channels that are coupled to ATP
synthase
- High-energy diffusion of H+ drives the reaction
ADP + P  ATP.
a. Energy from 1 NADH from glycolysis generate 2 ATP
b. Energy from 1 NADH from decarboxylation and the
citric acid cycle generate 3 ATP
c. Energy from 1 FADH2 generate 2 ATP for a total of
32 ATP
H+ combines with O- inside the mitochondria creating water (H2O)

45. Oxidative Phosphorylation
Occurs on a membrane, the mitochondrial cristae,
to generate most of the ATP produced from glucose
Figure 25–5b

46. Summary of Electron Transport
2 NADH from glycolysis + 2 NADH from decarboxylation + 6 NADH from Citric Acid Cycle + 2 FADH2 from Citric Acid Cycle + 6 O ATP + 32 P 
12 H2O + 32 ATP + 10 NAD+ + 2 FAD

47. Final Summary of Aerobic Respiration
C6H12O6 + 6 O ADP + 36 P 
6 CO2 + 6 H2O + 36 ATP
36 ATP:
2 from Glycolysis in cytoplasm
2 from Citric Acid Cycle by substrate level phosphorylation in matrix of mitochondria
32 from Electron Transport by oxidative phosphorylation in the cristae of the mitochondria

48. Energy Yield of Aerobic Metabolism
Figure 25–6

49. Lipid Catabolism: Beta–Oxidation
Figure 25–8 (Navigator)

50. Lipolysis – Lipid Catabolism
Hydrolyzes triglycerides (fat storage) 
glycerol and three fatty acids
Glycerol:
Glycerol  pyruvic acids in the cytoplasm
Pyruvic acid catabolized through TCA in mitochondria
Fatty Acids:
Fatty acids are catabolized by beta-oxidation into acetyl-CoA
In mitochondria to enter the TCA as two-carbon fragments
For each two-carbon fragment of fatty acid produced by beta-oxidation, the cell can generate 17 molecules of ATP
This is 1.5 times the energy production as with glucose
Generates more energy but requires more oxygen
Occurs much more slowly than equal carbohydrate metabolism

51. Amino Acid Catabolism
Figure 25–10 (Navigator)

52. Protein and Amino Acid Catabolism
1. Protein  amino acids
2. Amino group (-NH2) is removed from amino acid in process called deamination
Requires vitamin B6
3. Amino group is removed with conjunction with a hydrogen creating ammonia (NH3)
Toxic
4. Liver converts the NH3  urea
Harmless and excreted by the kidney
5. Remaining amino acid carbon chains are used at various stages in the Citric Acid Cycle to generate ATP
Amount of ATP produced varies

53. Protein and Amino Acid Catabolism
Not a Practical Source of Quick Energy
Typically only used in starvation situations
Harder to break apart than carbohydrates or lipids
Proteins are structural and functional parts of every cell
Thus tend to only be used when no other energy source is available
Amino acids are simply recycled by hydrolysis of peptide bonds in one protein, to be reassembled by dehydration synthesis into the next.

54. Nucleic Acid Catabolism
DNA is never catabolized for energy
RNA can be broken down into:
Simple sugars
Nitrogenous bases
Sugars:
Metabolized in glycolysis but only the pyrimidine bases (uracil and cytosine) can be processed in the TCA cycle
Purines (adenine and guanine) are deaminated and excreted as uric acid making RNA metabolism very inefficient
Typically nucleotides are simply recycled into new nucleic acid molecules and are not used for energy production

55. Pathways of Catabolism and Anabolism
Figure 25–12

56. What is the primary role of the TCA cycle in the production of ATP?
break down glucose
create hydrogen gradient
phosphorylate ADP
transfer electrons from substrates to coenzymes

57. How would a decrease in the level of cytoplasmic NAD affect ATP production in mitochondria?
ATP production would increase.
ATP production would decrease.
ATP production would fluctuate randomly.
ATP is not produced in mitochondria.

58. How would a diet that is deficient in pyridoxine (vitamin B6) affect protein metabolism?
It would interfere with protein metabolism.
It would enhance protein metabolism.
It would cause the use of different coenzymes.
Pyridoxine is not involved in protein metabolism.

59. Elevated levels of uric acid in the blood can be an indicator of increased metabolism of which organic compound?
nucleic acids
proteins
carbohydrates
lipids

60. SUMMARY Cellular metabolism Catabolism and Anabolism
Carbohydrate metabolism
Glycolysis
Cellular Respiration
Mitochondrial ATP production
Lipid catabolism (Beta-oxidation)
Amino acid catabolism
Protein synthesis