用于皮肤抗衰老的活性氧及抗氧化剂
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The toxicity of superoxide is due to the following reactions of this species.
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Mitochondrial electron transport chain
NO NO2 ONOO‐
Nitric oxide Nitrogen dioxide Peroxynitrite
Radical Radical no Radical
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Biological interrelations of O2• - and NO•
• •
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Reactive species - Definition
• Reactive species have a higher energy as the ground state. • Highly reactive in chemical or biochemical reactions. • Activation is necessary for a reaction under mild conditions. • Example: Oxygen is reduced in the electron transport chain (mitochondria) via different intermediates to water. • Reactive species are radicals and non radicals.
„Reactive oxygen species and antioxidants: Implication for skin aging” Hans-Jürgen Duchstein
University of Hamburg Institute of Pharmacy
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Biological effects of reactive oxygen species
O2
1
•-
O2
Proteins
OH•
Lipids Carbohydrates
H2O2
Nucleic acids
Cytotoxicity Mutagenicity Enzymeinhibition Cancerogenesis Enzymedestruction cytostatic effects TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
„Reactive oxygen species and antioxidants: implication for skin aging”
Questions:
Radicals or reactive species, oxygen and nitrogen? How these species are formed? How to measure these species? Influence of external stress Reactive species and antioxidants Reactive species and skin Reactive species and aging
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Biochemical formation of reactive oxygen species
O2
Lipidperoxidation Katalase
• HO 2
NADPH-Oxidase
H2O
Lipidperoxidation
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Activation of oxygen
O2 Me n+
+
coordinative Activation
2 * +∆ E (≈ 100 kJ)
1 ∆ O g 2
Me n+
2 *
3O
2
2 *
reductive Activation +1e
Biochemical mechanism of destruction and defense
Enzymatic and non enzymatic antioxidants
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Enzymatic antioxidants
Vitamin E
HO
Chemical and physical quenching of 1O2
O + OH• - H2O
Radicalscavenger
Vitamin E ( -Tocopherol)
•O
O
TOR ZUR WELT DER WISSENSCHAFT
Vitamin E Radical (Chromanoxyl-Radical) Resonance stabilized, therefore less reactive
GSH-Peroxidase
O2•H2O2
SOD
1
MPO Cl H2O2
O2
OCl
O2• -
-
O2• -
SOD Fe 2+
Lipidperoxidation
OH
•
H2O2
•+O 2
SOD = Superoxid-Dismutase MPO = Myeloperoxidase TOR ZUR WELT DER WISSENSCHAFT
•O2
O2
•-
•O2
•O2
百度文库
MnSOD (SOD 2)
• SOD reaction • Katalase reaction
•O2 +
2 H2 O 2
•O2
+ 2 H+
H2 O 2 + O2 2 H2 O + O 2
13.06.2012
TOR ZUR WELT DER WISSENSCHAFT
Non enzymatic antioxidants
O • 2
HO • 2
• Superoxide radical anion named by Pauling (1979) does not mean superoxidizing, but refers to the unusual configuration of the electrons. • The anion is at physiological pH a very weak oxidizing agent (pKa = 4,8). • The protonated form is much more reactive, but this is not formed in the body.
+
1∑ +O g 2
+∆ E (≈ 160 kJ)
electronic Activation
O 22 +2 H H O 2 2 +1e OH + OH •
O • 2 2 *
+1e -
2 *
13.06.2012
TOR ZUR WELT DER WISSENSCHAFT
Characterisation of superoxide
• The reaction between NO• und O2• ‐ is three times than the reaction of O2• ‐ and superoxid dismutase (SOD). • NO• is the only target molecule for superoxide, which can compete in the rate of reaction with the SOD catalyzed dismutation. • The influence of SOD to reduce the biological half life of NO•, is a very strong hint for the biological importance of this reaction.
• • • •
Chemical species with unpaired electrons e. g.: H• or NO•, and O2 . An unpaired electron has a magnetic moment and a spin quantum number. Radicals have 2 different orientations in a magnetic field douplet state. Biradicals like oxygen have 3 different orientations in a magnetic field triplet state. Radicals are not necessarily reactive species. Radicals react easy with other radicals.
•O2
•O2
O• 2
O2
•-
• Electron uptake never in a package 4 electrons Reductionsequivalents from of NADH • 4 One stepsto oxygen => are electron transferred to water • 1. Reduction Step: Formation of the superoxide anion radical [ 4H ] + O2 --> 2 H2O
13.06.2012
Non enzymatic antioxidants
Vitamin E and Vitamin C
HO HO HOH2C O
OH O
+ Vit. E - Vit. E
•
HO HO O
O
• + Vit. E - Vit. E •
O HO O
O O
H
HOH 2C
H
O
HOH 2C
H
• Synergism with ascorbic acid • Regeneration of Vitamin E • Scavenger of active oxygen species
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Superoxide toxicity and nitric oxide
• NO• - another player in the game
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Reactive nitrogen species (RNS)
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Oxygen - Groundstate
2 unpaired electrons, biradical, triplet state 3
O=O
O2
2 *
or
•O• 2
• Oxygen is unique in such a ground state • Most of the other molecules have paired electrons Spinbarrier between oxygen and the other molecules No reactions, although thermodynamic possible O2 must be activated, the spinbarrier has to be removed
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
What are reactive oxygen species?
• Radicals or something else?
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Radicals - Definition
Lipidperoxidation Membrane damage Arachidonic acid cascade
Desoxyribose damage Hyaluronic acid degradation
13.06.2012 13.06.2012
Lipidperoxidation
H
H H
-H •
e. g. initiated by OH•
•
+O
•H
but, similar products with singlet oxygen
2 + RH
•OO
-R
H HOO H
•
Formation of malondialdeyde TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Mitochondrial electron transport chain
NO NO2 ONOO‐
Nitric oxide Nitrogen dioxide Peroxynitrite
Radical Radical no Radical
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Biological interrelations of O2• - and NO•
• •
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Reactive species - Definition
• Reactive species have a higher energy as the ground state. • Highly reactive in chemical or biochemical reactions. • Activation is necessary for a reaction under mild conditions. • Example: Oxygen is reduced in the electron transport chain (mitochondria) via different intermediates to water. • Reactive species are radicals and non radicals.
„Reactive oxygen species and antioxidants: Implication for skin aging” Hans-Jürgen Duchstein
University of Hamburg Institute of Pharmacy
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Biological effects of reactive oxygen species
O2
1
•-
O2
Proteins
OH•
Lipids Carbohydrates
H2O2
Nucleic acids
Cytotoxicity Mutagenicity Enzymeinhibition Cancerogenesis Enzymedestruction cytostatic effects TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
„Reactive oxygen species and antioxidants: implication for skin aging”
Questions:
Radicals or reactive species, oxygen and nitrogen? How these species are formed? How to measure these species? Influence of external stress Reactive species and antioxidants Reactive species and skin Reactive species and aging
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Biochemical formation of reactive oxygen species
O2
Lipidperoxidation Katalase
• HO 2
NADPH-Oxidase
H2O
Lipidperoxidation
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Activation of oxygen
O2 Me n+
+
coordinative Activation
2 * +∆ E (≈ 100 kJ)
1 ∆ O g 2
Me n+
2 *
3O
2
2 *
reductive Activation +1e
Biochemical mechanism of destruction and defense
Enzymatic and non enzymatic antioxidants
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Enzymatic antioxidants
Vitamin E
HO
Chemical and physical quenching of 1O2
O + OH• - H2O
Radicalscavenger
Vitamin E ( -Tocopherol)
•O
O
TOR ZUR WELT DER WISSENSCHAFT
Vitamin E Radical (Chromanoxyl-Radical) Resonance stabilized, therefore less reactive
GSH-Peroxidase
O2•H2O2
SOD
1
MPO Cl H2O2
O2
OCl
O2• -
-
O2• -
SOD Fe 2+
Lipidperoxidation
OH
•
H2O2
•+O 2
SOD = Superoxid-Dismutase MPO = Myeloperoxidase TOR ZUR WELT DER WISSENSCHAFT
•O2
O2
•-
•O2
•O2
百度文库
MnSOD (SOD 2)
• SOD reaction • Katalase reaction
•O2 +
2 H2 O 2
•O2
+ 2 H+
H2 O 2 + O2 2 H2 O + O 2
13.06.2012
TOR ZUR WELT DER WISSENSCHAFT
Non enzymatic antioxidants
O • 2
HO • 2
• Superoxide radical anion named by Pauling (1979) does not mean superoxidizing, but refers to the unusual configuration of the electrons. • The anion is at physiological pH a very weak oxidizing agent (pKa = 4,8). • The protonated form is much more reactive, but this is not formed in the body.
+
1∑ +O g 2
+∆ E (≈ 160 kJ)
electronic Activation
O 22 +2 H H O 2 2 +1e OH + OH •
O • 2 2 *
+1e -
2 *
13.06.2012
TOR ZUR WELT DER WISSENSCHAFT
Characterisation of superoxide
• The reaction between NO• und O2• ‐ is three times than the reaction of O2• ‐ and superoxid dismutase (SOD). • NO• is the only target molecule for superoxide, which can compete in the rate of reaction with the SOD catalyzed dismutation. • The influence of SOD to reduce the biological half life of NO•, is a very strong hint for the biological importance of this reaction.
• • • •
Chemical species with unpaired electrons e. g.: H• or NO•, and O2 . An unpaired electron has a magnetic moment and a spin quantum number. Radicals have 2 different orientations in a magnetic field douplet state. Biradicals like oxygen have 3 different orientations in a magnetic field triplet state. Radicals are not necessarily reactive species. Radicals react easy with other radicals.
•O2
•O2
O• 2
O2
•-
• Electron uptake never in a package 4 electrons Reductionsequivalents from of NADH • 4 One stepsto oxygen => are electron transferred to water • 1. Reduction Step: Formation of the superoxide anion radical [ 4H ] + O2 --> 2 H2O
13.06.2012
Non enzymatic antioxidants
Vitamin E and Vitamin C
HO HO HOH2C O
OH O
+ Vit. E - Vit. E
•
HO HO O
O
• + Vit. E - Vit. E •
O HO O
O O
H
HOH 2C
H
O
HOH 2C
H
• Synergism with ascorbic acid • Regeneration of Vitamin E • Scavenger of active oxygen species
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Superoxide toxicity and nitric oxide
• NO• - another player in the game
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Reactive nitrogen species (RNS)
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Oxygen - Groundstate
2 unpaired electrons, biradical, triplet state 3
O=O
O2
2 *
or
•O• 2
• Oxygen is unique in such a ground state • Most of the other molecules have paired electrons Spinbarrier between oxygen and the other molecules No reactions, although thermodynamic possible O2 must be activated, the spinbarrier has to be removed
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
What are reactive oxygen species?
• Radicals or something else?
TOR ZUR WELT DER WISSENSCHAFT
13.06.2012
Radicals - Definition
Lipidperoxidation Membrane damage Arachidonic acid cascade
Desoxyribose damage Hyaluronic acid degradation
13.06.2012 13.06.2012
Lipidperoxidation
H
H H
-H •
e. g. initiated by OH•
•
+O
•H
but, similar products with singlet oxygen
2 + RH
•OO
-R
H HOO H
•
Formation of malondialdeyde TOR ZUR WELT DER WISSENSCHAFT
13.06.2012