Aging, Reactive Oxygen Species, and Antioxidants David B

1
Aging, Reactive Oxygen Species, and Antioxidants

• David B. Min
• Department of Food Science and Technology
• The Ohio State University

2
What Do We Concern Frequently in Our Life?
3
Can We Slow Down the Clock of Aging?
4
What is Aging ?
Aging is mainly due to the cumulative results of
free radical oxidation of the protein, lipid and
nucleic acid of our body.
5
Research Activities of Food Scientist on Free
Radical Oxidation

• The mechanisms and kinetics of free radical
  oxidation of protein, lipid, carbohydrate, and
  vitamins
• The formation and properties of reactive oxygen
  species, and their reaction rates with proteins,
  lipid and vitamins
• The chemical mechanisms and kinetics of
  antioxidants
• Food scientists and nutritionists have jointly
  studied the bioavailability and benefits of food
  antioxidants for health

6
Structural Features of Aging by Oxidation

• Dimerization or polymerization of lipids
• Cross linkage of proteins
• Fragments of DNA
• Formation of age pigment

7
Oxygen History
1772 Scheele Priestley Discovered
Oxygen 1811 Avogadro Oxygen is a Diatomic
Molecule 1848 Faraday Oxygen is a
Paramagnetic Molecule 1934 Herzberg
Observation of Singlet Oxygen 1969 Foote
Wexler Rediscovered Singlet Oxygen  
8
Oxidation of Biological Compounds

• Triplet oxygen oxidation
• Singlet oxygen oxidation

9
Electronic Configuration of Triplet Oxygen
Molecular
?
Atomic
Atomic
?
?
?
?
2Px 2Py 2Pz
2Pz 2Py 2Px
?
Energy
?
2S
2S
?
10
Lipid Oxidation
14 13 12 11 10 9
C
H
C
H
C
H
C
H
C
H
C
H
C
H
R
(
C
H
)
C
H
2
2
2
2
3
3
Initiation
Metal Reactive oxygen species
H
?
Preventive Antioxidants
13 12 11 10 9
(
C
H
)
C
H
C
H
R
C
H
C
H
C
H
C
H
C
H
2
2
4
3
?
E0 600mV
3O2
K109 M-1sec-1
11
(
C
H
)
C
H
C
H
C
H
C
H
C
H
C
H
R
C
H
2
4
3
2
O
3O2
H from RH (Lipid)
R ROO
O
Propagation
?
K 100 M-1sec-1
E01000mV
.
Radical Scavenging Antioxidant
O
H
O
C
(
C
H
)
(
C
H
)
C
H from
3
3
3
3
O
C
H
O
C
H
3
3
K 107 M-1sec-1
E0 400mV
12
C
H
C
H
C
H
C
H
C
H
C
H
R
(
C
H
)
C
H
2
2
4
3
O
E02300 mV
OH
?
O
H
(
C
H
)
C
H
C
H
C
H
C
H
C
H
C
H
R
C
H
2
4
3
2
O
E01600 mV
?
Termination
C
H
(
C
H
)
C
HO
3
2
4
(
C
H
)
C
H
C
H
C
H
C
H
C
H
C
H
R
C
H
2
3
4
2
O
O
(
C
H
)
C
H
C
H
C
H
C
H
C
H
C
H
R
C
H
3
2
2
4
13
Protein Oxidation
Protein cross linkage
R
O
R
O
R
O
O2
P
P
P
P
P
P
N
C
C
N
C
C
N
C
C


H
H
H
H
O
O
H
R
O
- OH
R
O
R
O
H
P
P
P
P
P
P
N
C
C
N
C
C
N
C
C
H
O
H
H
O

H
O
O
H
Peptide bond cleavage
14
DNA Oxidation
Nucleic Acids
Breaking by Oxidation
Reactive Oxygen Species
15
Effects of DNA Oxidation Damage on Body
Long Term Consequences
Aging
Cancer
Disease
16
Electronic Configuration of Singlet Oxygen
Molecular
?
Atomic
Atomic
?
?
?
?
2Px 2Py 2Pz
2Pz 2Py 2Px
?
Energy
?
2S
2S
?
17
Electron Spin Resonance Spectrum of
Tetramethyl-4-Piperidone-N-Oxyl of Singlet Oxygen
3370 G 3390 G
3410 G
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Reaction Rates of 3O2 and 1O2 with Foods
.
OOH
3O
3O
2
2
R
R
R
1
R
2
R
2
R
1
1
2
OOH
1O
O
2
R
R
R
R
H
1
2
2
O
1
OOH
gtgtgt
1O
3O
2
2
R
R
1
2
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Reactive Oxygen Species

• Reactive oxygen species are a collective term to
  include oxygen radicals and non radical oxygen
  derivatives.
• Reactive oxygen species are HO, RO, HOO, ROO,
  O2-, 1O2 and H2O2.
• Reactive oxygen species are formed by enzymatic,
  chemical, and photochemical reactions, and
  irradiation, and by the interactions among
  reactive oxygen species.

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Formation of Reactive Oxygen Species
.
2
R
O
O
H2O
-

H
e

H2O2
.
2HOO
3O2 3Sensitizer
.
H
O
Irradiation
Sensitizer
1
-

H
e
1O2
Fe3
.
2

-
F
H2O2 Fe2
e
O
H
H
O

-

H
e
H
Irradiation
.
H2O2
H
O
O
3

F
e
.
-
-
H
O

H
e
O

2
.
Sensitize
2
O
3
2

H
Sensitizer
O
aqe
3
-
O
3

3

2

2

R
Xanthine Oxidase
O
.
3
2
H
O
O
H
O
2
.
R
O
O
.
H2O2
H
O

21
Standard Electron Reduction Potential of Reactive
Oxygen Species
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Reaction Rates (M-1sec-1) of Reactive Oxygen
Species with Food Compounds
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Effects of Reactive Oxygen Species on
Degenerative Diseases for Aging
Heart
Skin
Gastro intestinal
Eye
Age pigment
Cataractogenesis
Heart attack
Hepatitis
Teeth Periodontis
Joints Arthritis
Reactive Oxygen Species
Multiorgan failure Cancer
Vessels Atherosclerosis
Lung Asthma
Brain Stroke
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Oxidative Stress
The oxidative stress leads to the aging of body.
Antioxidant
ROS
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Are You Ready to Fight the Reactive Oxygen
Species Attack?
O2-, 1O2, HO, H2O2, RO, ROO
Antioxidant
ROS Jail
R, RO, ROO, 1O2, O-2, .OH, H2O2,
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Relationship between Antioxidant and Health
Antioxidant
Heart disease

Cancer

Diabetes

Immune function


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Types of Antioxidants

• Preventive Antioxidants
• Prevention of free alkyl radical formation in
  initiation
• Singlet oxygen quenchers
• Antioxidant enzymes
• Radical Scavenging Antioxidants
• Prevention of peroxy radical chain reaction
  in propagation
• Hydrogen donating antioxidants

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Singlet Oxygen Quenching of ?-Carotene
Energy transfer
1O2 1?-Carotene 3O2 3?-Carotene
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Antioxidant Enzymes
Catalase
Superoxide dismutase
2O2- H2O2 O2
H2O
2H
Glutathione Oxidase
GSSG 2H2O
2GSH
Glutathione Reductase
NADP
NADPH H
NADP Reductase
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Hydrogen Donating Antioxidant

• Antioxidant should donate a hydrogen to peroxy
  radical, which is mainly responsible for free
  radical chain reaction in biological system.

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Mechanism and Radical Resonance Stabilization of
Antioxidant
O
H
C
(
C
H
)
3
3

ROO (Lipid or Protein Radical)
ROOH
O
C
H
E01000mV
3
.
O
O
.
C
(
C
H
)
C
(
C
H
)
3
3
3
3
O
C
H
O
C
H
3
3
E0 400mV
O
O
C
(
C
H
)
C
(
C
H
)
.
3
3
3
3
.
O
C
H
O
C
H
3
3
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Standard Electron Reduction Potentials of Peroxy
Radical and Antioxidants
33
Bond Dissociation Energy of Antioxidant Hydroxyl
Group
H
O
H
CH3
H
OCH3
H
34
Change in Bond Dissociation Energy of Phenolic
Antioxidant
OH
87
35
Reaction Rate Constant of a-Tochopherol with
Peroxy Radical in Biological System

• Medium K (M-1sec-1)
• Hydrophobic System 7 106
• Aqueous System 8 105
• Phospholipid bilayer 3 103

Trolox
36
Antioxidants and Enzymes in Body
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Conclusion
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Effects of Reactive Oxygen Species on
Degenerative Diseases for Aging
Heart
Gastro intestinal
Skin
Eye
Age pigment
Cataractogenesis
Heart attack
Hepatitis
Teeth Periodontis
Joints Arthritis
Reactive Oxygen Species
Multiorgan failure Cancer
Vessels Atherosclerosis
Lung Asthma
Brain Stroke
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Formation of Reactive Oxygen Species
.
2
R
O
O
H2O
-

H
e

H2O2
.
2HOO
3O2 3Sensitizer
.
H
O
Irradiation
Sensitizer
1
-

H
e
1O2
Fe3
.
2

-
F
H2O2 Fe2
e
O
H
H
O

-

H
e
H
Irradiation
.
H2O2
H
O
O
3

F
e
.
-
-
H
O

H
e
O

2
.
Sensitize
2
O
3
2

H
Sensitizer
O
aqe
3
-
O
3

3

2

2

R
Food
Xanthine Oxidase
O
.
3
2
H
O
O
H
O
2
.
R
O
O
.
H2O2
H
O

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Are You Ready to Fight the Reactive Oxygen
Species Attack?
O2-, 1O2, HO, H2O2, RO, ROO
Antioxidant
ROS Jail
R, RO, ROO, 1O2, O-2, .OH, H2O2,
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How to Slow Down the Clock of Aging?

• Extensive research indicates that reactive oxygen
  species are partly responsible for aging process.
  
• The generous consumption of antioxidant rich
  fruits and vegetable helps slow down aging
  process.
• Do moderate exercise to increase the activities
  of antioxidant enzymes and immune function.

42
How to Slow Down the Clock of Aging?

• Relatively low calorie diet to decrease the
  production of reactive oxygen species during
  metabolism.
• Avoid the environmental conditions and personal
  behaviors which increase reactive oxygen species.

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• Aging, Reactive Oxygen Species, and Antioxidants
• What Do We Concern Frequently in Our Life?
• Can We Slow Down the Clock of Aging?
• What is Aging ?
• Research Activities of Food Scientist on Free
  Radical Oxidation
• Structural Features of Aging by Oxidation
• Oxygen History
• Oxidation of Biological Compounds
• Electronic Configuration of Triplet Oxygen
• Lipid Oxidation
• Protein Oxidation
• DNA Oxidation
• Effects of DNA Oxidation Damage on Body
• Electronic Configuration of Singlet Oxygen
• Electron Spin Resonance Spectrum of
  Tetramethyl-4-Piperidone-N-Oxyl of Singlet Oxygen
• Reaction Rates of 3O2 and 1O2 with Foods
• Reactive Oxygen Species
• Formation of Reactive Oxygen Species
• Standard Electron Reduction Potential of Reactive
  Oxygen Species

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• Effects of Reactive Oxygen Species on
  Degenerative Diseases
• Oxidative Stress
• Are You Ready to Fight the Reactive Oxygen
  Species Attack?
• Relationship between Antioxidant and Health
• Types of Antioxidants
• Singlet Oxygen Quenching of ?-Carotene
• Antioxidant Enzymes
• Hydrogen Donating Antioxidant
• Mechanism and Radical Resonance Stabilization of
  Antioxidant
• Standard Electron Reduction Potentials of Peroxy
  Radical and Antioxidants
• Bond Dissociation Energy of Antioxidant Hydroxyl
  Group
• Change in Bond Dissociation Energy of Phenolic
  Antioxidant
• Reaction Rate Constant of a-Tochopherol with
  Peroxy Radical in Biological System
• Antioxidants and Enzymes in Body
• Conclusion
• Formation of Reactive Oxygen Species
• Effects of Reactive Oxygen Species on
  Degenerative Diseases
• Are You Ready to Fight the Reactive Oxygen
  Species Attack?
• How to Slow Down the Clock of Aging?