ANTIOKSIDAN

Oleh:
Nurrahman
 Defenses against Prooxidants
1. Prevention of prooxidant formation

2. Interception of prooxidants

3. Breaking the chain of radical reactions

4. Repair of damage caused by prooxidants

ANTIOXIDANT: a substance that is able, at relatively low concentrations,

to compete with other oxidizable substrates and, thus, to significantly delay
or inhibit the oxidation of other substrates
Prevention of prooxidant formation
Physical prevention:
Behavioral: - avoidance
Barriers: - organismal level
- organ level
- cellular level

Biochemical prevention:
Control of prooxidant molecules:
- transition metal chelators
- catalytic control of O2 reduction
Control of prooxidant enzymes:
- blockade of stimuli
- inhibition of enzymes
Examples of preventative ‘antioxidants’

Anti-inflammatory agents
Nitric oxide synthase inhibitors
Metal chelators:
- Metallothionein
- Transferrin
- Lactoferrin

NADPH oxidase inhibitors

Xanthine oxidase inhibitors
 Interception of prooxidants
‘Classical’ antioxidant:
Intercepts species, once formed
Excludes from further damaging activity
Transfers species from critical parts of
cell

Important considerations for interception reactions:

Speed of reaction (rate constant)
Concentration of intercepting species in vivo
Is reaction truly a detoxication pathway?
Is reaction catalytically recyclable?
 Chain breaking antioxidants
Example of radical chain-reaction: lipid peroxidation
ROO• (peroxyl radicals) are often the chain-carrying radicals
Chain-breaking oxidants act by reacting with peroxyl radicals:

“Donor” antioxidants (tocopherol, ascorbate, uric acid,…)

LOO• + TOH LOOH + TO•

“Sacrificial” antioxidants (Nitric oxide):

LOO• + NO• LOONO

Good chain-breaking antioxidant:

both ANT and ANT• should be relatively UNreactive
ANT• decays to harmless products
does not add O2 to make a new peroxyl radical
is renewed (recycled)
 Cellular antioxidants
Small Molecules
-Water soluble: glutathione, uric acid, ascorbate (Vit. C)
-Lipid soluble: -tocopherol (Vit. E), -carotene, coenzyme Q

Proteins
-Intracellular: SOD (I and II), glutathione peroxidase, catalase
-Cell membrane: SOD (III), ecGPx, plasma proteins (e.g. albumin)
-Extracellular: phospholipid hydroperoxide GPx (PHGPx)
 ‘Antioxidant Network’
Catalytic maintenance of antioxidant defense
Non-scavenging enzymes (re-reduce antioxidants)
Dependence on energy status of cell
Glucose is the most important ‘antioxidant’

Catalytic reduction of peroxides Catalytic reduction of lipid radicals

ROOH ROH LOO. LOO

G-SeH G-SeOH Tocopherol Tocopheroxyl radical

GPx
Ascorbate
Ubiquinone
GSSG 2 GSH
GSSG Dehydroascorbate
reductase Ubiquinol

NADPH NADP+
GSH GSSG
G6PDH
6-phosphogluconate glucose-6-phosphate NAD(P)+ NAD(P)H
Repair of damage caused by prooxidants

Protection not perfect

Repair of damaged products

proteins and lipids
-rereduction and degradation
DNA
-repair enzymes

Cell death (apoptosis/necrosis)

 Antioksidan
 Antioksidan adalah substansi yang
diperlukan tubuh menetralisir
radikal bebas dan mencegah
kerusakan yang ditimbulkan o/
radikal bebas dengan melengkapi
kekurangan elektrolit yg dimiliki
radikal bebas dan menghambat
terjadinya reaksi berantai dari
pembentukan radikal bebas yg dpt
menimbulkan stres oksidatif
 Antioksidan
 Vit A
 Vit C
 Vit E
 Karotenoid
 selenium
Vitamins Alpha Breaks lipid peroxidation Fat soluble
tocopherol Lipid peroxide and O2·⁻ and ·OH vitamin
scavenger

Beta carotene Scavenges ·OH, O2·⁻ and peroxy Fat soluble

radicals vitamin
Prevents oxidation of vitamin A
Binds to transition metals

Ascorbic acid Directly scavenges O2·⁻, ·OH, and Water soluble

H2O2 vitamin
Neutralizes oxidants from
stimulated neutrophils
Contributes to regeneration of
vitamin E
 Vitamin E
 Family of related compounds
 tocopherols & tocotrienols
 tocotrienols less widely distributed than
tocopherols - considered of less nutritional
importance
 4 major forms based on # & position of
methyl groups on ring - , , , 
 all-rac tocopherol
 CH 3
HO H 3C CH 3
H 3C H H
2 -Tocopherol
H 3C O 4' 8' CH 3 Activity
CH 3
CH 3 roughly
corresponds to
number of
methyl groups
 Carotenoids

• About 600 identified so far

• Most familiar is yellow-orange pigments of
carrots, -carotene
• Two major groups: carotenes and xanthophylls
 Carotene Groups

Caroteniods

carotenes xanthophylls

ά-carotene Β-carotene crypto-

lutein zeaxanthin
xanthin
 Ascorbic acid (vitamin C)

 Biochemical function:
cofactor for at least eight
enzymes
 At the tissue level, a major
function  collagen
synthesis ( vit C deficiency
can lead scurvy)
 The antioxidant
properties protect NO,
protect against age-related
cataract
 Fruits

• Grapes
• Berry fruits
• Prunes
• Citrus fruits
• Apples
 Vegetables

Tomato Beans
Broccoli Beet
Mushroom Corn
White cabbage Kale
Cauliflower Spinach
Garlic Onion
 Soybean

R2 O

R1 O
OH

Isoflavone R1 R2
Genistein OH OH
Genistin OH O-glucose
Daidzein H OH
Daidzin H O-glucose
 Herb and Spice

OH CH3 OH CH3
HO HO
CH3 O CH3
HOOC C

H3C CH3 H3C CH3

Carnosoic Acid Carnosol

OH
HOOC

O OH

HO
OH Rosemarinic Acid
 Tea

OH

OH
OH

O HO O
HO OH
OH

OH
OH
OH
OH

Epicatechin Epigallocatechin
 Biological Activities of Phytochemicals

• Antioxidants Carotenoids tocopherol

catechins quercetin
kaempferol genistein
daidzein
• Anticancer Agent s Isoflavones lignans
• DNA repair Agents Vanillin cinnamaldehyde
coumarin anisaldehyde
Terima kasih