1. Announcements My Pyramid extra credit project is due TODAY!
You should have turned your labs in/made up your quizzes already.
Cell/Pedigree extra credit projects are due next week.

2. Announcements FINAL EXAM cumulative 2 hrs starts at 11am in this room
you can use a periodic table and calculator
NO CELL PHONES!

3. Announcements
Celebrate the end of Bio 099 at the Outback Steakhouse next Saturday from 2-4pm
Here’s the address:
615 Bel Air Rd
Bel Air MD 21014

4. An overview of Metabolism
Bio 099
December 8, 2007

5. Metabolism
Metabolism is all the chemical reactions that occur in a living organism.

6. Catabolism
Catabolism is the breakdown or digestion of organic molecules.
Catabolic reactions release energy in the form of ATP, which the cell can then use for its various functions.

7. What molecules does the cell break down for energy?
Usually fats and carbohydrates are the fuel of choice
Triglycerides =
fatty acids + glycerol
Glycogen =
monosaccharides

8. Glycogen most abundant storage of carbohydrate
a branched chain of glucose molecules

9. Triglycerides
most abundant storage of lipids
primarily of fatty acids

10. Proteins most abundant organic components in body
perform many vital cellular functions

11. Metabolism Handout

12. Tools for making ATP To survive cells need to make ATP.
For ATP synthesis the following are required:
oxygen

13. Tools for making ATP To survive cells need to make ATP.
For ATP synthesis the following are required:
oxygen
nutrients/vitamins

14. Tools for making ATP To survive cells need to make ATP.
For ATP synthesis the following are required:
oxygen
nutrients/vitamins
mitochondria

15. Tools for making ATP To survive cells need to make ATP.
For ATP synthesis the following are required:
oxygen
nutrients/vitamins
mitochondria
enzymes

16. Why are catabolic reactions necessary for the cell?
To release energy for anabolic reactions!

17. Anabolism
Anabolism is the production of new organic molecules using cellular energy (ATP).
For example:
Proteins are produced through an anabolic reaction that uses ATP to form polypeptide bonds between amino acids.

18. Why is anabolism necessary?
Metabolic Turnover: The cell needs energy to periodically replace its components.
Growth and Division: In order to grow and divide a cell needs energy.
Special Processes: Depending on the specific cell type, various functions require energy.
For example: muscle cell contraction requires energy.
Nutrient Pool: A cell keeps a reserve storage of nutrients, just in case…

19. Catabolism: Aerobic Cellular Respiration

20. Aerobic Cellular Respiration: generating ATP for the cell
Glycolysis
Krebs cycle (TCA)
Electron transport chain

21. Aerobic Cellular Respiration
Glycolysis
Krebs cycle (TCA)
Electron transport chain
happens only in the presence of oxygen
aerobic: requires or takes place in the presence of oxygen

22. Mechanisms of ATP synthesis
substrate-level phosphorylation
occurs during glycolysis and Kreb’s cycle
ADP + P  ATP
oxidative phosphorylation
occurs during the electron transport chain
formation of a proton (H+) gradient across the inner mitochondrial membrane provides potential energy to make ATP

23. Oxidation-reduction (redox) reactions are important in metabolism
Oxidation: a molecule is oxidized when it loses electrons.
Reduction: a molecule is reduced when it gains electrons.
During metabolism enzymes catalyze these reactions

24. Example of a redox reaction: NAD+
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that carries electrons to be used in the electron transport chain.
NAD+ is made from the vitamin niacin.

25. Example of a redox reaction: FAD+
flavin adenine dinucleotide (FAD) is a coenzyme that carries electrons to be used in the electron transport chain.
FAD contains riboflavin (vitamin B2).

26. Carbohydrate Catabolism
generates ATP by breaking down sugar
C6H12O6 + 6O2 6H2O + 6CO2 = 36 ATP + heat
1 molecule of glucose nets 36 molecules of ATP

27. Glucose must first get into the cell
insulin binds to its receptor to tell the cell glucose is coming and to add glucose transporter proteins to the membrane.
glucose is transported into the cell through facilitated diffusion

28. Carbohydrate Metabolism
Glycolysis: always happens first.

29. Glycolysis
STEP 1.
Hexokinase phosphorylates glucose creating glucose-6-phosphate
uses 1 ATP molecule
traps glucose molecule within cell

30. Glycolysis
STEP 2.
Phosphoglucoisomerase transforms glucose-6-phosphate to fructose-6-phophate

31. Glycolysis
STEP 3.
Phosphofructokinase (PFK) adds a phosphate to fructose-6-phophate making it Fructose 1, 6 bisphosphate.
This reaction requires 1 ATP.

32. Glycolysis
STEP 4.
An enzyme splits Fructose 1, 6 bisphosphate into 2 glyceraldehyde-3-phosphates molecules.

33. Glycolysis
STEP 5.
Each glyceraldehyde-3-phosphate is oxidized to 1,3-bisphosphoglycerate.
At the same time NAD+ is reduced to NADH.
NAD+ also donates a phosphate group in the reaction

34. Glycolysis
STEP 6.
Each 1,3-bisphosphoglycerate is striped of its phosphate groups making 3-Phosphoglycerate.
The phosphates are used to generate ATP from ADP (2 total)

35. Glycolysis
STEP 7&8.
2 more enzymatic reactions form phosphoenolypyruvate (PEP).

36. Glycolysis
STEP 9.
PEP is converted to pyruvate generating ATP

37. Glycolysis
Each Glucose makes 2 molecules of glyceraldehyde phosphate so from that point on, multiply everything by 2:
= 2 NADH
= 4 ATP

38. Glycolysis: Take home message
ATP is used in 2 reactions at the beginning of glycolysis:

39. Glycolysis: Take home message
ATP is used in 2 reactions at the beginning of glycolysis:
to keep glucose in the cell
to make the molecule that is then broken in half

40. Glycolysis: Take home message
ATP is used in 2 reactions at the beginning of glycolysis:
to keep glucose in the cell
to make the molecule that is then broken in half
4 ATP and 2 NADH are generated in the last half of glycolysis,

41. Glycolysis: Take home message
ATP is used in 2 reactions at the beginning of glycolysis:
to keep glucose in the cell
to make the molecule that is then broken in half
4 ATP and 2 NADH are generated in the last half of glycolysis
2 pyruvate molecules are generated from glycolysis.

42. Carbohydrate Metabolism
Glycolysis
Pyruvic acid transition

43. The fate of pyruvic acid
In the absence of oxygen (anaerobic)
The Electron Transport Chain (ETC) cannot run because O2 is the final electron acceptor
Because NADH2 cannot unload its H ions in the ETC it returns them to pyruvic acid forming lactate
This often happens in the muscle cells during exercise

44. The fate of pyruvic acid
By the way…
this is also how we make alcohol from sugar: fermentation

45. The fate of pyruvic acid
In the presence of oxygen (aerobic)
First, Pyruvic acid will enter the mitochondria where it is converted to acetyl CoA:

46. The fate of pyruvic acid
In the presence of oxygen (aerobic)
First, Pyruvic acid will enter the mitochondria where it is converted to acetyl CoA:
CO2 is removed
H ions leave and reduce NAD+ to NADH2
coenzyme A is added giving acetyl CoA

47. The fate of pyruvic acid
In the presence of oxygen (aerobic)
First, Pyruvic acid will enter the mitochondria where it is converted to acetyl CoA:
CO2 is removed
H ions leave and reduce NAD+ to NADH2
coenzyme A is added giving acetyl CoA
Next, Acetyl CoA enters the Krebs Cycle and continues aerobic cellular respiration.

48. Carbohydrate Metabolism
Glycolysis
Pyruvic acid transition
Kreb’s cycle

49. Kreb’s Cycle (TCA, citric)
Acetyl CoA combines with oxaloacetic acid to form citric acid

50. Kreb’s Cycle (TCA, citric)
Acetyl CoA combines with oxaloacetic acid to form citric acid
as the cycle continues carbons are removed, forming CO2 and NAD/FAD are reduced to NADH/FADH (electron carriers)

51. Kreb’s Cycle (TCA, citric)
Acetyl CoA combines with oxaloacetic acid to form citric acid
as the cycle continues carbons are removed, forming CO2 and NAD/FAD are reduced to NADH/FADH (coenzymes and electron carriers)
1 ATP molecule is made via substrate-level phosphorylation

52. The Krebs Cycle Overall Reactants Overall Products Acetyl-CoA 3 NAD+
FAD
ADP and Pi
Overall Products
Coenzyme A
2 CO2
3 NADH
FADH2
ATP
Remember: 1 glucose molecule will give double of every reactant and product!

53. What do you get when 1 glucose molecule is broken down via aerobic respiration?
Glycolysis:
2 ATP via substrate-level phosphorylation
2 NADH2
Transition Reaction (pyruvate to acetyl CoA):
Krebs Cycle:
6 NADH2
2 FADH2
2 ATP
36 Total
ATP

54. Metabolism Handout:
note that lipid and protein break-down also form molecules that enter the Kreb’s cycle.

55. Electron Transport Chain (ETC)
Oxygen must be present!
Finally we will see the fate of the coenzymes (NADH, FADH2).

56. the fate of NADH2 and FADH
NADH and FADH drop off H ions (and e-) at the ETC in the mitochondria.

57. Electron shuttling
e- are shuttled through a sequence of membrane proteins (electron carriers).

58. H+ pumping
this provides energy to pump H ions against their concentration gradient
inner membrane matrix
intermembrane space

59. Electron carriers and H+ pumps
Two types of proteins in the inner mitochondrial membrane shuttle e- and/or pump H+.

60. Electron carriers and H+ pumps
Two types of proteins in the inner mitochondrial membrane shuttle e- and/or pump H+.
complexes I-IV

61. Cytochromes
Two types of proteins in the inner mitochondrial membrane shuttle e- and/or pump H+.
complexes I-IV
cytochromes
Cytochromes are proteins with heme groups that require Fe, S and Cu.

62. Electron carriers and H+ pumps
Two types of proteins in the inner mitochondrial membrane shuttle e- and/or pump H+.
complexes I-IV
cytochromes
Cytochromes are proteins with heme groups that require Fe, S and Cu.

63. Electron carriers and H+ pumps
Two types of proteins in the inner mitochondrial membrane shuttle e- and/or pump H+.
complexes I-IV
cytochromes
Cytochromes are proteins with heme groups that require Fe, S and Cu.
Coenzyme Q is not a protein, but still carries e-.

64. Oxidative Phosphorylation: ADP  ATP
The H+ gradient creates energy to power the ATP synthase complex.

65. Oxidative Phosphorylation: ADP  ATP
The H+ gradient creates energy to power the ATP synthase complex.
As H+ rush back into the matrix through the ATP synthase protein, ADP is phosphorlyated

66. Oxidative Phosphorylation: ADP  ATP
The H+ gradient creates energy to power the ATP synthase complex.
As H+ rush back into the matrix through the ATP synthase protein, ADP is phosphorlyated
This process is also known as chemiosmosis

67. ETC animation

68. Oxidative Phosphorylation: how many ATP are made?
NADH from glycolysis:
2 ATP in electron transport chain
exception is cardiac muscle = 3 ATP in ETC
NADH from pyruvate transition reaction:
3 ATP in electron transport chain
NADH from Kreb’s cycle:
FADH2 from Kreb’s cycle:

69. Total ATP production from 1 molecule of glucose

70. Total ATP production from 1 molecule of glucose

71. Metabolism Handout:
Now we will add in the side arrows.

72. Storing carbohydrate energy: Glycogenesis
Carried out in liver and muscle

73. Utilizing stored energy: Glycogenolysis:
breaking down glycogen to glucose
carried out in liver

74. making carbs from other sources: Gluconeogenesis
Formation of glucose from fatty acids and amino acids
basically glycolysis in reverse
happens in the liver

75. Metabolism Handout:
Now we will add in the side arrows.

76. Lipid Metabolism: digestion
fats are digested, absorbed and put into chylomicrons (large lipoprotiens).

77. Lipid Metabolism: digestion
fats are digested, absorbed and put into chylomicrons (large lipoproteins).
Chylomicrons enter the blood stream where triglycerides are extracted.
The remnant of the chylomicron goes to the liver

78. Metabolism Handout:
Now we will add in the side arrows.

79. Lipid Metabolism: digestion
The triglycerides are broken down further in the blood to free fatty acids + glycerol.

80. The fate of glycerol
glycerol is converted to glyceraldehyde-3-phosphate
G-3-P enters glycolysis and then goes through Kreb’s cycle and the ETC.

81. The fate of free fatty acids: Beta-oxidation
Fatty acids are broken down into 2 carbon acetic acid fragments.
the acetic acid is converted to acetyl-Co A, which enters the Krebs cycle and then ETC
How much ATP does a 18 carbon fatty acid chain produce?

82. Storing fat: Lipogenesis

83. Utilizing stored energy: lipolysis
Breakdown of lipids
converted to G-3-P and enters glycolysis
converted to acetyl-CoA and enters Kreb’s cycle

84. Ketogenesis
KREB’S
If you are on a low-carb diet, starving yourself, or diabetic:
oxaloacetic acid (from breakdown of glucose) levels decline and slow down the turning of the Kreb’s cycle
acetyl Co-A (from fatty acid breakdown) accumulates and the liver converts it to ketone bodies
Ketone bodies are released into the
blood so they can be eliminated by the
kidneys
excess ketones in blood = ketoacidosis

85. Metabolism Handout:
Now we will add in the side arrows.

86. Protein Metabolism
Generally, proteins are not used for energy because we need them for protein synthesis (essential amino acids)
Ammonia
Keto Acid
Urea
pyruvate
Kreb’s cycle
acetyl CoA

87. Overview of Catabolism
glucose =
glycolysis
fatty acids =
beta-oxidation
amino acids =
deamination

88. Overview of Anabolism We talked about: Glycogenolysis Gluconeogenesis
Lipogenesis
Cells also use ATP to make proteins and nucleic acids.