Reactive Oxygen Species in the Body, Antioxidant...

1

Reactive Oxygen Species

in the Body

Antioxidant Defence

MUDr Jan Plaacuteteniacutek PhD

Uacutestav leacutekařskeacute biochemie a laboratorniacute diagnostiky 1LF UK

What is a free radical

- any chemical species (molecule atom ion)

capable of independent existence that contains

at least one unpaired electron

O2middotndash

radical ion

molecule

2

For what do we need oxygen

Transfer of electrons (oxidation) from organic substances tooxygen releases huge amount of energy

Eg Glucose

CC66HH1212OO66 + 6 O+ 6 O22 rarrrarrrarrrarr 6 CO6 CO22 + 6 H+ 6 H22OO

∆∆∆∆∆∆∆∆GGoorsquorsquo = = ndashndash 2820 2820 kJkJ mol mol (180 g (180 g of of glugluccososee))

In addition reactivity of oxygen can be controlled by catalysiswith transition metals (iron copper)

Does sugar burn

3

4

Spin restriction of dioxygen

bull Normal (triplet) O2 is a biradical with high affinity to electrons

bull But gain of an electron requires one of the unpaired electrons changes its spin which is a slow process

bull Thatrsquos why we do not burn in the air

bull Singlet O2 is an excited highly reactive species

Respiratory chain in the

mitochondrial inner

membrane

5

The respiratory chain

Electrons flow lsquodownhillrsquo and terminate at oxygen

Overall reaction

NADH + H+ + 12 O2 rarrrarrrarrrarr NAD+ + H2O

∆∆∆∆∆∆∆∆GGoorsquorsquo = = ndashndash21925 kJ mol21925 kJ mol--11

hellipand resulting proton gradient powers ATP synthesis

6

Reactive oxygen species (ROS lsquooxygen radicalsrsquo) can be derived from intermediates of oxygen reduction to water

O2

2H2O

+4 e-

(+4 H+)

O2middotndash

superoxide

H2O2hydrogen peroxide

OHmiddothydroxyl

radical

+3 e-

(+3 H+)

+2 e-

(+2 H+)

+1 e-

( +H2O )

Superoxidebull Sources in the body

ndash Escape of electrons to oxygen

- Respiratory chain in mitochondria

- Other similar redox carrier systems eg microsomalcytochrome P450 monooxygenase

ndash NAD(P)H Oxidase

- Phagocytes (rdquorespiratory burstrdquo)

- Non-phagocytic cells

ndash Some enzymes

- Xanthine oxidase

- Cyclooxygenase

- Lipoxygenase

ndash Reaction of FeII-hemoglobin with oxygen

ndash Autoxidation (reaction with oxygen) of various compounds (ascorbate glutathione and other thiols catecholamines)

O2middotndash

7

Superoxide production in the respiratory chain

bull 1-2 of total body oxygen consumption (from in vitro experiments in vivo surely much less)

bull Escape of electrons from redox centers of complexes I and III mostly from semiquinone

Origin of superoxide from oxyhemoglobin

Štiacutepek S et al Antioxidanty a volneacute radikaacutely ve zdraviacute a nemoci GradaPublishing Praha 2000

8

Superoxide

bull Properties

- Moderate reactivity both oxidising and reducing agent

- Limited ability to cross biological membranes (only through anion channels or in its protonated form)

- Releases iron from Fe-S clusters

bull Fate

ndash Dismutation

ndash Reaction with nitric oxide

O2middotndash

O2middotndash + O2

middotndash + 2 H+ rarr O2 + H2O2

NO + O2middotndash rarr OONOndash (peroxynitrite)

Hydrogen peroxide

bull Formation in the body

ndash Dismutation of superoxide (spontaneous or catalyzed by superoxide dismutase)

ndash Directly by action of some enzymesbull Xanthine oxidase

bull Monoamine oxidase (MAO)

H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties

- No radical- Freely crosses biological membranes- Fairly unreactive as such- But rapidly reacts with reduced transition metals such

as iron copper (the Fenton reaction)

bull Fate

ndash The Fenton reaction

ndash Safe decomposition by glutathione peroxidase peroxiredoxin or catalase

H2O2

H2O2 + Fe2+ rarr OHndash + OHmiddot + Fe3+

hydroxyl radical

Hydroxyl radical


ndash Ionising radiation


bull Properties

- Extremely high reactivity Damages biomolecules near its site of formation

OH middot


H2O rarr H + OHmiddot

10

Reactive Oxygen Species (ROS)bull Radicals

ndash Superoxide O2middotndash

ndash Hydroperoxyl radical HO2middot

ndash Hydroxyl radical OHmiddotndash Peroxyl radicals ROOmiddotndash Alkoxyl radicals ROmiddot

bull Non-radicalsndash Hydrogen peroxide H2O2

ndash Hypochlorous acid HClOndash Ozone O3

ndash Singlet oxygen 1O2

Nitric oxide


ndash NO synthase-catalysed reaction

ndash Three different NO synthases- NOS I (neuronal constitutive)- NOS II (phagocytes inducible)- NOS III (endothelial constitutive)

NO middot

L-Arginine + O2 + NADPH rarr L-Citrulline + NADP+ +NO

11

Nitric oxidebull Properties- Gaseous radical- Reaction with heme iron of guanylate cyclase

(hellipphysiological effects)- Reaction with heme iron of hemoglobin (hellipinactivation)

- Reaction with sulfhydryl groups on glutathione etc to nitrosothiol (helliptransportstorage)

- Reaction with superoxide to peroxynitrite and finally hydroxyl radical (helliptoxicity)

NO middot

NO + O2middotndash rarr OONOndash peroxynitrite

OONOndash + H+ rarr HOONO rarr OHmiddot + NO2

peroxynitrous acid hydroxyl radical

NO causes relaxation of smooth muscles in blood

vessel wall

12

Reactive Nitrogen Species (RNS)bull Radicals

ndash Nitric oxide NOndash Nitric dioxide NO2

bull Non-radicalsndash Nitrosonium NO+

ndash Nitroxyl NOndash

ndash Nitrous acid HNO2

ndash Dinitrogen trioxide N2O3

ndash Dinitrogen tetraoxide N2O4

ndash Nitronium NO2+

ndash Peroxynitrite ONOO ndash

ndash Alkylperoxynitrite ROONO

Oxidative damage to biomolecules

bull Lipids peroxidation of polyunsaturated fatty acids in membranes

bull Proteins oxidation of -SH carbonylation -NH2 hydroxylationnitrosylation of aromatic AA cross-linking degradation

bull Nucleic acids strand breaks hydroxylation of bases mutation cancerogenesis

13

Lipid peroxidationLipid peroxidation((rancidityrancidity))

Further fate of lipid peroxides

14

Ionising radiationHydroxyl radical originates from ionisation of water

H2O + hν rarr H + OHmiddot

Reactive oxygen species in the body

One-electron reduction of oxygen (mitochondria NADPH oxidase) forms superoxide O2

middotndash

Dismutation of superoxide produces hydrogen peroxideO2

middotndash + O2middotndash + 2 H+ rarr O2 + H2O2

Fenton reaction with Fe or Cu converts peroxide tohydroxyl radicalH2O2 + Fe2+ rarr OHndash + OHmiddot + Fe3+

Where RONS are beneficial

I Active centers of some enzymes

bull Monooxygenases (cytochromes P450)

bull Ribonucleotide reductase (hellipDNA synthesis)

bull Synthesis of prostanoids (enzymatic lipoperoxidation)

bull Useful heme peroxidasesndash Thyreoid peroxidase

ndash Myeloperoxidase of neutrophils

ndash Lactoperoxidase in milk respiratory tract mucus and saliva

15




ndash Detoxication of drugs synthesis of steroid hormones andbile acids NO synthases

Mechanism in essence controlled Fenton reaction

Fe3+ + SH + 2 e- + O2 + H+ rarr FeOOH SH

FeOOH SH rarr FeO3+ SH + H2O

FeO3+ SH rarr FeOH3+Sbull rarr Fe3+SOH rarr Fe3+ + SOH


II Signaling

bull Eg nitric oxide NOndash Smooth muscle relaxation in blood vessels

gastrointestinal tract corpus cavernosum penis

ndash neurotransmitter neuromodulator in CNS function in synaptic plasticity learning andmemory

ndash Inhibition of adhesion and aggregation of platelets

ndash Inhibition of adhesion of leukocytes

ndash (etc)

Superoxide as well with effects opposing NO

16

NITRIC OXIDEProduced by NO synthases

Vasodilation inhibition of leukocyte activation inhibition of platelet

aggregation etc

SUPEROXIDEPEROXIDEProduced by NADPH oxidasesVasoconstriction activation of

leukocytes aggregation of platelets etcAnd if meet destroy each other

NO + O2middotndash rarr OONOndash

Concept of redox signaling

bull Redox environment inside the cell ndashdetermined mostly by ratios GSHGSSG and NADHNAD

bull Redox sensors on proteinsndash critical -SH groups

ndash Fe-S centers

bull Targets of redox signalingndash transcription factors

ndash protein kinases and phosphatases

17

Redox signaling

bull Oxidative stress activatescertain protein kinases andtranscription factors

bull Effect of ROSantioxidant on the cell can be veryspecific eg stimulationof proliferationdifferentiation cellularsenescence (ageing) orapoptosis

(T Finkel amp NJ Holbrook Nature 408 (2000) 239-247)


III Phagocytosis

bull Neutrophils eosinophils monocytes macrophages microglia

bull Often the target particle needsto be marked (coated withopsonins)

bull Phagocyte tasksndash Recognizendash Engulfndash Killndash Digest

copy 1998 Garland Publishing

18

Fig httpwalchecklabumnedu_rsrc1417821135388research-interestsneutrophil-recruitment

Activation of a phagocytic cell Respiratory burst

bull Dramatic increase in consumption of oxygen (for superoxide production not respiration)

bull Dramatic increase in consumption of glucose(for the pentose cycle ndash produces NADPH forNADPH oxidase)

19

NADPH oxidase

bull Membrane enzyme producing a superoxide fluxoutwardly or into a phagosome

bull Catalyzes reactionNADPH + 2O2 rarr NADP+ + H+ + 2O2middotndash

bull Latent in resting cell assembles on the cell membrane from 6 subunits during phagocyteactivation

bull Necessary for an ability to kill some kinds of engulfed bacteria (hereditary deficit chronicgranulomatous disease)

bull Similar enzymes are present also on theendothelial and many other non-phagocytic cells

Myeloperoxidase

bull 2 ndash 5 of total protein in neutrophils

bull Hemoprotein that gives pus its green tinge

bull Non-specific peroxidase in the body catalyzes reaction

Clminus + H2O2 + H+ rarr HClO + H2O

bull Deficit in humans is common (1 in 2000-4000) and is not severe

20

Further neutrophil weaponsbull Powerful proteolytic enzymes elastase collagenase

cathepsin G gelatinase etcbull Lysozyme cleaves polysaccharide of Gram+ bacterial

cell wallbull Lactoferrin binds iron to make unavailable for bacteriabull Defensins cationic proteins forming channels in

bacterial cell membranebull NETs (neutrophil extracellular traps) fibers of DNA

and serine proteases catch bacteria extracellularly

RONS generators and other weapons can synergizeeg HClO inhibits α1-antitrypsin

RONS as phagocyte weapons

iNOS is important in macrophage but rather insignificant in human neutrophils In contrast macrophages do not possessmyeloperoxidase

21

Oxidative stress

bull Levels of reactive oxygen species are kept within certain limits by mechanisms of antioxidant defence

bull Oxidative stress occurs if the oxidantantioxidant balance shifts to oxidation

Antioxidant defence

bull prevention of ROSRNS formation (regulation of producing enzymes sequestration of metals)

bull scavenging trapping and quenching of radicals

bull reparation systems (phospholipases proteasome DNA repair)

22

Antioxidant in food chemistry

bull Reducing agent capableof terminating chainreaction of lipid peroxidation hellipldquochain-breakingrdquo

bull Egndash Butylated

hydroxytoluene (BHT)

ndash Butylated hydroxyanisol(BHA)

ndash Tocopherol (Vitamin E)

Antioxidant defence of human body

bull Anatomy of the body limiting tissue oxygen

bull Antioxidant enzymes

bull Sequestration of redox active metals

bull Antioxidant substrates (scavengers)

bull Stress response

bull (Repair systems)

23

O2

First organism

(anaerobic)

Developantioxidantdefence

Die out

Resort to anaerobic

condition

O2Clump together

O2

24

Antioxidant defence I

Regulation of tissue O2

Inhaled air 160 mmHg O2

Lung capillaries 100 mmHg O2

Arterial blood 85 mmHg O2

Arterioles 70 mmHg O2

Capillaries 50 mmHg O2

Cells 1-10 mmHg O2

Mitochondria lt 05 mmHg O2

Fig Wikipedia

Antioxidant defence II

Antioxidant enzymes

bull Superoxide dismutase

O2middotndash + O2


bull Catalase

2 H2O2 rarr 2 H2O + O2

bull Glutathione peroxidase peroxiredoxin H2O2 + 2 R-SHrarr 2 H2O + RS-SR

25

Superoxide dismutase (SOD)bull Catalyses dismutation of superoxide

O2middotndash + O2


bull Absolutely required for life in oxygen

bull SOD1 Cu+Zn (cytosol of eukaryotic cells)

bull SOD2ndash Mn (mitochondrial matrix)

ndash Fe (bacteria)

bull EC-SOD (SOD3) extracelullar Cu+Zn ndash MW 135000 binds to heparane sulfate on the

inner surface of blood vessels

Glutathione peroxidases (GPX)bull Reduction of peroxides coupled to oxidation of

glutathione2 GSH + H2O2 rarr GS-SG + 2 H2O

(glutathione is subsequently regenerated by glutathione reductases)

bull Active site contains selenocysteine

bull Cytosolic glutathione peroxidasendash reduces H2O2 and LOOH after release from

phospholipids

bull Phospholipide hydroperoxide-GSH-peroxidasendash reduces LOOH even in membranes

26

Glutathione (GSHGSSG)bull tripeptide in every cell

1-10 mM

bull keeps ICT reduced

bull substrate for GPX etc

bull also non-enzymatic reactions with ROS and mixed disulfides with proteins products of GSH oxidation are toxic for cell

bull in oxidative stress the cell exports GSSG out

Catalasebull Tetramer every subunit contains heme with

Fe

bull Dismutation of hydrogen peroxide


bull Red blood cells peroxisomes

bull Also peroxidase activity

H2O2 + ROOH rarr H2O + ROH + O2

(in comparison to GPX less significant)

27

OxidaOxidationtion of very longof very long chain fattychain fatty acids in peracids in peroxisomeoxisomess

Glutathioneperoxidase

H2O2

H2O

Glutathionereductase

GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash

Superoxide dismutase

Reduced glutathione(GSH)

Oxidised glutathione(GS-SG)

ATPATP

28

PeroxiredoxinThioredoxin

bull Recently discovered antioxidant system more important for removal of hydrogen peroxide than GPX

H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29

Antioxidant defence III

Sequestration of metalsbull Redox-active transition metals (Fe Cu)

acceptdonate one electron easilyndash alleviation of spin restriction of dioxygenndash metals are in active centers of all oxygen handling-

enzymes

bull But the same properties of Fe Cu are deleterious if uncontrolledndash the Fenton oxidant


oxidative damage to biomolecules


Sequestration of metalsbull Ironcopper handling proteins

ndash transferrin binds 2 atoms Fe3+ (transport)ndash lactoferrin analogous to transferrin but no Fe

release ( only sequestration) leucocytes ndash ferritin H and L subunits H is ferroxidase Fe

storage (up to 4500 atoms Fe3+) ndash haptoglobin binds hemoglobin in circulationndash hemopexin binds heme in circulationndash ceruloplasmin contains Cu function

ferroxidase (export Fe from the cells)ndash albumin transport of Cu

30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu

Superoxide dismutaseGlutathione peroxidaseCatalase

GlutathioneTocopherolAscorbate

Antioxidant enzymes amp

glutathione levels very low

TocopherolAscorbateCarotenoids uric acid albumin

glucose bilirubin

Labile iron pool (LIP) present Sequestration of iron and copper- transferrin lactoferrin- hemopexin- haptoglobin- ceruloplasmin (ferroxidase)- Cu bound to albumin

bull THIOLS ndash Glutathionendash Thioredoxin

bull OTHER ENDOGENOUS METABOLITESndash Bilirubin ndash Uric acidndash Lipoic acid

bull DIETARYndash Ascorbate (Vitamin C)ndash α-Tocopherol (Vitamin E)ndash Carotenoidsndash Plant phenols

Antioxidant defence IVLow-molecular-weight antioxidant substrates

31

Tocopherols (Vitamin E)

bull group of 8 isomers α-tocopherol most effective

bull antioxidant ofmembranes(lipophilic)

bull ldquochain-breakingrdquo terminates thechain reaction of lipid peroxidation

Ascorbate (Vitamin C)

bull Redox-active saccharide

bull In most animals synthesized from glucuronic acid

bull Vitamin for humans other primates bats and guinea pigs

bull Deficit causes scurvy (scorbut)

32

Ascorbate in the bodybull Main function is pro-oxidant cofactor of hydroxylases

ndash Hydroxylation of Pro and Lys in collagen synthesisndash Synthesis of noradrenaline from dopaminendash Synthesis of carnitine (hellip role in oxidation of fat)ndash Activation of hypothalamic peptidic hormones by

amidation (CRH GRH oxytocin vasopressin substance P)

bull Reductant for iron promotes its intestinal absorptionbull Potentially dangerous pro-oxidant if iron sequestration

impaired (hemochromatosis) ()bull Daily need 70-100 mg high doses po excreted by

urine (renal threshold cca 200 mg24 hours)

membrane compartment hydrophilic compartment

LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-

dehydroascorbatereductase

2GSH

GSSG

33

Activated neutrophiles

accumulate

dehydroascorbate (DHA)GLUT1

DHA

Ascorbate

Protects membrane of the neutrophilefrom its own ROS

GSH

GSSG

Glutaredoxin

bull Selenium

ndash Trace element (daily need 55 microg) possibility of deficiency as well as intoxication

ndash Component of several antioxidant enzymes(glutathione peroxidase thioredoxin reductase) and also eg 5lsquo-dejodase

bull ββββ-carotene (provitamin A) is precursor forsynthesis ofndash Retinal hellip vision

ndash Retinoic acid hellipregulator of gene expression cellular growth and differentiation

34

Antioxidant defence V

Stress responseOxidation or nitrosylation of sensor -SH

Transcription factors (NFκB Nrf-2hellip)activation nuclear translocation

Induction of gene expressionbull chaperones (heat shock proteins)bull antioxidant enzymes

bull metallothioneinbull hemoxygenase 1

helliprarr more resistant to further

oxidative stress

Apoptosis as theultimate antioxidant defence

2

For what do we need oxygen

Transfer of electrons (oxidation) from organic substances tooxygen releases huge amount of energy

Eg Glucose

CC66HH1212OO66 + 6 O+ 6 O22 rarrrarrrarrrarr 6 CO6 CO22 + 6 H+ 6 H22OO

∆∆∆∆∆∆∆∆GGoorsquorsquo = = ndashndash 2820 2820 kJkJ mol mol (180 g (180 g of of glugluccososee))

In addition reactivity of oxygen can be controlled by catalysiswith transition metals (iron copper)

Does sugar burn

3

4







mitochondrial inner

membrane

5



Overall reaction




6


O2

2H2O

+4 e-

(+4 H+)

O2middotndash

superoxide


OHmiddothydroxyl

radical

+3 e-

(+3 H+)

+2 e-

(+2 H+)

+1 e-

( +H2O )








ndash Some enzymes

- Xanthine oxidase

- Cyclooxygenase

- Lipoxygenase



O2middotndash

7






8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


3

4







mitochondrial inner

membrane

5



Overall reaction




6


O2

2H2O

+4 e-

(+4 H+)

O2middotndash

superoxide


OHmiddothydroxyl

radical

+3 e-

(+3 H+)

+2 e-

(+2 H+)

+1 e-

( +H2O )








ndash Some enzymes

- Xanthine oxidase

- Cyclooxygenase

- Lipoxygenase



O2middotndash

7






8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


4







mitochondrial inner

membrane

5



Overall reaction




6


O2

2H2O

+4 e-

(+4 H+)

O2middotndash

superoxide


OHmiddothydroxyl

radical

+3 e-

(+3 H+)

+2 e-

(+2 H+)

+1 e-

( +H2O )








ndash Some enzymes

- Xanthine oxidase

- Cyclooxygenase

- Lipoxygenase



O2middotndash

7






8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


5



Overall reaction




6


O2

2H2O

+4 e-

(+4 H+)

O2middotndash

superoxide


OHmiddothydroxyl

radical

+3 e-

(+3 H+)

+2 e-

(+2 H+)

+1 e-

( +H2O )








ndash Some enzymes

- Xanthine oxidase

- Cyclooxygenase

- Lipoxygenase



O2middotndash

7






8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


6


O2

2H2O

+4 e-

(+4 H+)

O2middotndash

superoxide


OHmiddothydroxyl

radical

+3 e-

(+3 H+)

+2 e-

(+2 H+)

+1 e-

( +H2O )








ndash Some enzymes

- Xanthine oxidase

- Cyclooxygenase

- Lipoxygenase



O2middotndash

7






8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


7






8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


8

Superoxide

bull Properties




bull Fate

ndash Dismutation


O2middotndash

O2middotndash + O2



Hydrogen peroxide





H2O2

O2middotndash + O2


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


9

Hydrogen peroxide

bull Properties



bull Fate



H2O2


hydroxyl radical

Hydroxyl radical




bull Properties


OH middot



10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


10








Nitric oxide




NO middot


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


11





NO middot





vessel wall

12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


12















13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


13



14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


14





middotndash












15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


15










II Signaling






ndash (etc)


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


16



aggregation etc







ndash Fe-S centers



17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


17

Redox signaling





III Phagocytosis





18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


18





19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


19

NADPH oxidase






Myeloperoxidase






20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


20









21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


21

Oxidative stress



Antioxidant defence




22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


22














23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


23

O2

First organism

(anaerobic)


Die out

Resort to anaerobic

condition

O2Clump together

O2

24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


24








Cells 1-10 mmHg O2


Fig Wikipedia


Antioxidant enzymes


O2middotndash + O2


bull Catalase



25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


25


O2middotndash + O2





ndash Fe (bacteria)








phospholipids


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


26


1-10 mM






Fe







27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


27



H2O2

H2O


GS-SG

GSHTranshydrogenase

NADPH+H+

NADP+

NADH+H+

NAD+

Pentose cycle

O2middotndash




ATPATP

28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


28



H2O2

GSH

O2middotndash


H2O

Thioredoxin

reductase RED

Thioredoxin

reductase OX

NADPH+H+

NADP+

SH HS

S S

Peroxiredoxin

RED

Peroxiredoxin

OX

SH HS

S S

Thioredoxin

RED

Thioredoxin

OX

FADH2 (Se)

FAD (Se)

29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


29




enzymes










30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


30

ICT ECT

Superoxide

Peroxide FeCu

Superoxide

Peroxide FeCu






glucose bilirubin






31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


31










32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


32








LH

L

Tocopherol

Tocopheryl

radical

LOOH

LOO

chain reaction of

lipid peroxidation

Ascorbate

Semidehydro-

ascorbate

Dehydroascorbate

+e-

-e-


2GSH

GSSG

33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


33


accumulate


DHA

Ascorbate


GSH

GSSG

Glutaredoxin

bull Selenium





34







oxidative stress


34







oxidative stress


Reactive Oxygen Species in the Body, Antioxidant...

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Transcript of Reactive Oxygen Species in the Body, Antioxidant...