1. Visual Anatomy & Physiology First Edition Martini & Ober
Chapter 22
(Sections )
Metabolism & Cellular Respiration
Lecture 8
Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1]
Slides 16 – 38; 50 min [Lecture 2]
118 min (38 slides plus review of course Web sites and syllabus)

2. Lecture Overview Enzymes and control of metabolic reactions
Energy and metabolic reactions
Cellular respiration
Overview
ATP as the biological energy carrier
Oxidation/Reduction
Steps in Cellular Respiration
Glycolysis
The Citric Acid (Krebs) Cycle
The Electron Transport Chain
Relationship of anabolism to catabolism

3. Enzymes and Metabolic Reactions
Enzymes – Biological catalysts
control rates of metabolic reactions
lower activation energy needed to start reactions
globular proteins with specific shapes
not consumed in chemical reactions
substrate specific
shape of active site determines which substrate(s) the enzyme can act on
Figure from: Hole’s Human A&P, 12th edition, 2010

4. Globular vs. Fibrous Proteins
Globular protein – an enzyme attached to its inhibitor
Fibrous protein – the structural protein, collagen

5. Enzymes Lower Activation Energy
Enzymes lower the barriers that block chemical reactions, i.e., they lower the activation energy needed to begin energetically favorable reactions

6. Control of Metabolic Reactions
Metabolic pathways
series of enzyme-controlled reactions leading to formation of a product
each new substrate is the product of the previous reaction
Factors that alter activity of enzymes
heat
radiation
substrate concentration
required cofactors
changes in pH
Enzyme names commonly
reflect the substrate
have the suffix – ase
sucrase, lactase, protease, lipase, hydrolase, oxidase

7. Cofactors and Coenzymes
make some enzymes active
ions or coenzymes
Coenzymes
complex organic molecules that act as cofactors (so coenzymes ARE cofactors)
vitamins
NAD+
Vitamins are essential organic substances that human cells cannot synthesize, i.e., they must come from the diet
- required in very small amounts
- examples - B vitamins: Thiamine (B1), niacin
The protein parts of enzymes that need a nonprotein part (coenzymes, cofactors) to work are called apoenzymes

8. Overview of Cellular Metabolism
Metabolism – All the chemical reactions that occur in an organism
KEEP THIS OVERALL SCHEME IN MIND AS WE GO INTO DETAILS!!
ETS
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

9. Overview of Glucose Breakdown
Figure from: Hole’s Human A&P, 12th edition, 2010

10. Overview of Cellular Metabolism
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

11. Overview of Catabolism
Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011

12. A Closer Look at Mitochondria
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001
(Impermeable to charged or polar molecules)
Strategically placed in cell where ATP demand is high
Outer mitochondrial membrane is very porous – ions and other small mol up to about 5 KDa. Inner membrane imperm to ions/small molecules, but contains transporter proteins (carriers) for nucleotides, fuel molecules. FA oxidation and the TCA cycle occur in the matrix.
Concentration of enzymes in the matrix is so high that there is virtually no hydrating water. Enzyme-linked reactions and pathways are so crowded that normal rules of diffusion do not apply!

13. Carbohydrate Metabolism
Most cells generate ATP and other energy-yielding compounds via the catabolism of carbohydrate (and fats)
General Reaction sequence in carbohydrate catabolism
C6H12O O2  6 CO H2O + ENERGY
If the above reaction happened all at once, all the chemical energy contained in the carbohydrate would be DISSIPATED AS HEAT.
How does the body harness the energy from carbohydrates?

14. Harnessing Energy - Stepwise Breakdown of Carbohydrates
Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

15. Energy for Metabolic Reactions
ability to do work or change something (potential, kinetic)
heat, light, sound, electricity, mechanical energy, chemical energy
changed from one form to another, but NEVER destroyed (law of conservation of energy)
involved in all metabolic reactions
Release of chemical energy
most metabolic processes depend on chemical energy
oxidation of glucose generates chemical energy
cellular respiration releases chemical energy slowly from molecules and makes it available for cellular use

16. Oxidation and Reduction Revisited
gain of O2
loss of e-
loss of H (since a H carries an electron with it)
increase in oxidation number, e.g., Fe2+ -> Fe3+
Reduction
loss of O2
gain of e-
gain of H
decrease in oxidation number, e.g., Fe3+ -> Fe2+
Oxidation can actually be defined as any of the following: 1) gain of oxygen 2) loss of H 3) loss of electrons 4) increase in oxidation number
Reduction can actually be defined as any of the following: 1) loss of oxygen 2) gain of H 3) gain of electrons 4) decrease in oxidation number
Oxidation Is Loss of electrons; Reduction Is Gain of electrons
“OIL RIG”

17. Energy of Organic Molecules
Carbohydrates like glucose store a great deal of chemical energy (as H·)
As carbohydrates (C6H12O6) are oxidized to CO2 they liberate their energy and lose electrons and H (H·)
But there must be molecules to accept these electrons, i.e., some molecules must be reduced.
In cellular respiration, O2 becomes the final electron (H·) acceptor and is reduced to H2O

18. Harnessing Energy from Carbohydrates
General Reaction sequence in carbohydrate catabolism
C6H12O O2  6 CO H2O + ENERGY
OXIDATION
REDUCTION
Electrons (H·) “fall” in energy from organic molecules to oxygen during cellular respiration.
That is, e- LOSE potential energy during this process and this energy is captured to make ATP
However, electrons CANNOT be transferred directly from glucose to the electron transport chain. There are intermediates – activated carrier molecules

19. Activated Carrier Molecules
Some activated carriers: ATP, NADH, FADH2, GTP, NADPH
Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

20. ATP – An Activated Carrier Molecule
Figure from: Hole’s Human A&P, 12th edition, 2010
each ATP molecule has three parts:
an adenine molecule
a ribose molecule
three phosphate molecules in a chain
These two components together are called a ?
ATP carries its energy in the form or P (phosphate)
ATP is a readily interchangeable form of energy for cellular reactions (“common currency”)
High-energy bonds

21. NAD(H) – An Activated Carrier Molecule
NAD (and NADP) are specialized to carry high-energy e- and H atoms
A “packet” of energy = H·
NADH + H+
NAD+
NADH
These packets of energy will be passed to oxygen in the electron transport chain, and their energy used to drive the synthesis of ATP
Important carriers of e- in catabolism: NADH, FADH2
Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

22. Overview of Cellular Respiration
Anaerobic
Cellular respiration
(aerobic)
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

23. Overview of Glucose Breakdown
Figure from: Hole’s Human A&P, 12th edition, 2010

24. Overview of Glucose Breakdown
Occurs in three major of reaction series…
Glycolysis (glucose to pyruvate; in cytoplasm)
Citric acid cycle (finishes oxidation begun in glycolysis; in the matrix of mitochondria)
Electron transport chain (uses e- transfer to make ATP; on inner membranes of mitochondria)
Produces
carbon dioxide
water
ATP (chemical energy)
heat (energy has changed form from chemical)
Includes
anaerobic reactions (without O2) - produce little ATP
aerobic reactions (requires O2) - produce most ATP

25. Glycolysis series of ten reactions
breaks down glucose (6C) into 2 molecules of pyruvic acid (pyruvate) (3C)
occurs in cytosol
anaerobic phase of cellular respiration (that is, it can continue to work with OR without O2)
yields 2 ATP and 2 NADH molecules per glucose
ADP + Pi
ATP
Glucose (6C)
2 Pyruvate (3C)
NAD+
NADH

26. Overview of Glycolysis
glucose (6C) → 2 pyruvate (3C)
Products of glycolysis
ATP
NADH
Pyruvate
Figure from: Hole’s Human A&P, 12th edition, 2010
NADH cannot enter the mitochondria directly. Its e- are transported via the glycerol phosphate shuttle (handed to FADH2) or the malate-aspartate shuttle (NADH is regenerated). NADH yields 2.5 ATP, while FADH2 yields 1.5 ATP.
NOTE what happens with and without O2 being available…

27. Metabolism of Pyruvate Without O2
process of forming lactate from glucose is anerobic glycolysis
important for regenerating NAD+ so glycolysis can continue to generate ATP for the cell O2
Pyruvic acid (pyruvate)
Lactic acid (lactate)
NADH + H+
NAD+
NAD+
NADH + H+
Glucose (6C)
2 Pyruvate (3C)
ADP + Pi
ATP

28. Overview of Aerobic Reactions
Figure from: Hole’s Human A&P, 12th edition, 2010
If oxygen is available –
pyruvic acid is used to produce acetyl CoA
citric acid (Krebs) cycle begins
electron transport chain functions
carbon dioxide and water are formed
maximum of 36 molecules of ATP produced per glucose molecule

29. Citric Acid Cycle In mitochondria… What happens…
Figure from: Hole’s Human A&P, 12th edition, 2010
In mitochondria…
What happens…
- Acetyl CoA enters cycle - Citric Acid is converted to various intermediates
- Several important products are produced in these interconversions of citric acid…
ATP is produced
NAD+ is reduced to NADH and FAD is reduced to FADH2
CO2 produced

30. Source of e- for the Electron Transport Chain
Figure from: Hole’s Human A&P, 12th edition, 2010
Notice the flow of electrons to the Electron Transport Chain

31. Electron Transport Chain
NADH and FADH2 carry electrons to the ETC
ETC series of electron carriers located in cristae of mitochondria
energy from electrons transferred to ATP synthase
ATP synthase catalyzes the oxidative phosphorylation of ADP to ATP
water is formed
*Chemiosmosis
Figure from: Hole’s Human A&P, 12th edition, 2010

32. Oxidative Phosphorylation
Chemiosmosis, Chemiosmotic coupling, or Chemiosmotic phosphorylation
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

33. Summary of Cellular Respiration
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

34. Is This All the Metabolism There Is?
Definitely NOT!
Notice how many lines connect pyruvate and Acetyl CoA to the rest of metabolism

35. Intermediates of Metabolism
Acetyl CoA (2C) and Pyruvate (3C) are important:
Allow interconversion of different types of molecules so cell’s needs can be met
Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011

36. Summary of Catabolism of Proteins, Carbohydrates, and Fats
Figure from: Hole’s Human A&P, 12th edition, 2010
Summary of Catabolism of Proteins, Carbohydrates, and Fats
Acetyl CoA is a common intermediate in the breakdown of most fuels.
Acetyl CoA can be generated by carbohydrates, fats, or amino acids
Acetyl CoA can be converted into fatty acids

37. Pyruvate is a Key Junction in Metabolism
Pyruvate is used to synthesize amino acids and Acetyl CoA
Pyruvate can also be used to synthesize glucose via gluconeogenesis.
 Glycogenesis
 Lipo-genesis
Glycogenolysis 
Lipolysis  *
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

38. Carbohydrate Storage Excess glucose can be
stored as glycogen by glycogenesis (liver and muscle cells)
stored as fat by lipogenesis
converted to amino acids
Figure from: Hole’s Human A&P, 12th edition, 2010

39. Terms to Know… Glycolysis – metabolism of glucose to pyruvate
-olysis  breakdown of neo  new -genesis  creation of
Glycolysis – metabolism of glucose to pyruvate
Gluconeogenesis – metabolism of pyruvate to glucose (making CHO from non-CHO source)
Glycogenesis – metabolism of glucose to glycogen
Glycogenolysis – metabolism of glycogen to glucose
Lipolysis – breakdown of triglyceride into glycerol and fatty acids
Lipogenesis – creation of new triglyceride (fat)

40. Review Enzymes are biological catalysts
Highly specific for their substrate
Lower activation energy needed to start a reaction
Are not consumed during reaction
May require cofactors/coenzymes
Effectiveness is greatly affected by temperature, pH, and the presence of required cofactors
The goal of metabolism is to provide the cell with energy (catabolism) and materials for the manufacture of cellular components (anabolism)

41. Review
Cells derive energy mainly from carbon compounds like carbohydrates and fats
These substances contain a great deal of energy stored in their chemical bonds
This energy must be liberated in stepwise fashion
Activated carriers serve as intermediates to capture the energy liberated at each step
Energy is the ability to do work
May be potential or kinetic
Changes form
Is never destroyed (only converted to another form)

42. Review
Carbohydrates yield energy as they are oxidized to CO2 and O2 is reduced to H2O
There are three main steps in extracting energy (in the form of ATP) from carbohydrates
Glycolysis
Citric Acid (Krebs) Cycle
Electron Transport Chain (ETC)
Electrons “fall” to lower states of energy in the ETC, giving up energy that is used to synthesize ATP

43. Review GLYCOLYSIS CONVERSION STEP KREBS CYCLE ELECTRON TRANSPORT CHAIN
LOCATION
cytoplasm
mitochondria
Mitochondrial matrix
Mitochondrial cristae (inner membrane
Oxygen
Required? no
yes
Starting
Product
glucose
(6-C)
2 pyruvates
(2 x 3C)
Acetyl CoA
(2 x 2C)
10 NADH
2 FADH2
End-
Products
(2 x 3-C)
2 ATP
2 NADH
2 Acetyl CoA
2 CO2
6 NADH
4 CO2
24 ATP
4 ATP
TOTAL
32 ATP

44. Review Anabolism is intimately tied to catabolism
Energy derived from catabolism is used to drive anabolic reactions
Some molecules are important junctions between catabolism and anabolism
Acetyl CoA
Generated from pyruvate, fatty acids, and amino acids
Can be used to synthesize fatty acids and other molecules
CANNOT be used to generate pyruvate
Pyruvate
Can be synthesized from glucose and amino acids
can be used to synthesize amino acids, glucose and acetyl CoA
NOTE, however, that in humans fatty acids cannot be converted to glucose