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Reactive Oxygen Species

(ROS)
Antioxydant
Virhan Novianry

Oxygen exists in the air as a diatomic


molecule (O2). Living organisms use
it to oxidise hydrocarbons to obtain
energy necessary for their
lifereduced into non toxic water
three intermediate steps:

Each orbital can maximally bear two


electrons with antiparallel spins
FREE RADICALS ARE DEFINED AS
CHEMICAL SPECIES (ATOMS OR
MOLECULES) WHICH CONTAIN
UNPAIRED ELECTRONS

Asal ROS
1. Respirasi : OH, O, HO2
2. Metabolisme asam lemak : radikal
peroksil (ROO*) radikal alkaloxyl
(RO*)
. ROS : memiliki unsur atom O, selain
itu terdapat radikat lain e.g : carbon
(R), sulphur (RS) or nitrogen (RN)

ROS non-radical
hydrogen peroxide (H2O2)
singlet dioxygen(O2) or
hypochlorous acid (HOCl)
relatively stable but they can be precursors for the generation of more
reactive species
Free radicals could be stabilized in several ways:
If two radicals meet, they can combine their unpaired electrons and
create a covalent bond.
If the free radical reacts with a non-radical molecule two cases may
arise:
i) The free radical may release its unpaired electron (reducing radical).
ii) The free radical may accept the electron from the other molecule
(oxidizing radical).
2nd choice (i et ii) cause chain reaction, non-radical molecule becomea
raddical

Superoxide anion radical (O-)


1. reduction product of dioxygen
synthesized by phagocytic cells to inactivate
pathogens or
involved in inter-cellular signalization processes
and grown regulation
2. not belong to highly toxic substances for cells.
3. It is a weak oxidizing agent but a stronger
reducing agent
4. CAN OXIDISE ASCORBIC ACIDS OR THIOLS

PEMBENTUKAN
Dioxygen is bonded inside the HEME-type active site of
cytochrome

metal ion is oxidized by molecular oxygen (Mn+ can be Fe2+, Cu+


etc.)

autoxidation of ubisemiquinone inside the mitochondria


membrane
Re-oxidizing process of flavin by molecular oxygen
transformation xanthine into uric acid

Re-oxidizing process of flavin by


molecular oxygen
transformation xanthine into uric
acid

Hydroxyl radical (OH)


the most aggressive free radical via
diffusion controlled rates
Sources:
radiolysis of water
decomposition of H2O2
1. Fenton reaction
2. Haber Weiss reaction

Toxic effects of ROS on


biomolecules
Membrane and lipid peroxidation
(1)Initiation of lipid peroxidation
(2) Propagation of lipid peroxidation

(3) Termination of lipid peroxidation

Terminasi
two peroxyl radicals meet
two carbon-centred radicals meet
peroxyl radical and carbon-centred
radical meet

Proteins damage by ROS

DNA Damage
hydroxyl radical (all base)
Singlet oxygen reacts only with
guanine
Malondialdehyde condensation (of
aldehydes) with adenine, guanine or
cytosine

Strategy of antioxidant
defence
Objectives :
to remove oxygen or to decrease local
oxygen concentration
to remove metal ions catalysing ROS
formation
to remove ROS (e.g., O2-, H2O2, OH)
to break the radical chain reaction
to regenerate endogenous antioxidants
to inhibit pro-oxidant enzymes

Prevention
Metal chelation would prevent their formation that , catalyse
by particularly iron and copper ions.
Eg : Proteins (e.g., ferritin and transferrin) or enzymes (e.g.,
gluthathione S-transferases)

Interception
Enzymatic antioxidants
Superoxide dismutase (SOD)
Catalase
Gluthathione peroxidase (GPx)

Non-enzymatic
antioxidants
-tocopherol (vitamin E)

Carotenoids

Ascorbic acid (vitamin C)

aktif terhadap oxygen-,


nitrogen- or sulphur-centred

Gluthatione (GSH)

Reparation
When prevention and interception
fail oxidative products are formed
and accumulate in tissues
i) DNA repair,
ii) degradation of the damaged
proteins or
iii) metabolization of lipid
hydroperoxides formed during lipid
peroxidation

Antioxidant properties of
polyphenolic compounds
inhibit enzymes which are
associated with the production of
ROS (e.g., xanthine oxidase,
cyclooxygenases or lipoxygenases)
1. the presence of the 5OH and 7OH
groups
2. the presence of the 2,3-double bond
3. the absence of the 3OH group

deactivate free metal ions (e.g.,


Fe2+, Cu2+, etc.) which can catalyse
decomposition of hydroxyl peroxide
into high reactive OH free radicals

directly scavenge ROS


i) the capacity of the compound to
donate electron or proton to free
radicals
ii) the capacity of the new radical to
be stabilized by p-electron
delocalization

i) Coupled protonelectron
transfer (CPET)
ii) Electron transferproton
transfer (ET-PT)

iii) Sequential proton loss-electron


transfer (SPET)

iv) The forth possible mechanism is


the formation of adducts