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7/22/2019 Biological Antioxidants
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7/22/2019 Biological Antioxidants
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WHAT IS FREE RADICAL?
A FREE RADICAL IS AN ATOM OR MOLECULE,
CAPABLE OF EXISTING INDEPENDENTLY,
WHICH CONTAINS ONE OR MORE UNPAIRED
ELECTORNS
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WHAT ARE ANTIOXIDANT NUTRIENTS?
ANTIOXIDANTS ARE COMPOUNDS WHICH
READILY DONATE ELECTRONS OR HYDROGEN
WITHOUT THEMSELVES BEING CONVERTED
INTO HIGHLY REACTIVE MOLECULES
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DEFENCE MECHANISMS
WATER
ENZYMIC SYSTEMS
ANTIOXIDANTS:
- VITAMINS- MINERALS
- SYNTHETIC ANTIOXIDANTS
- PLANT PHENOLS AND INDOLES
- ORGANOSULPHURS
- URIC ACIDS
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PRO-OKSIDAN ANTI-OKSIDAN
RADIKAL BEBAS NON RADIKAL
ENZIM
NON-ENZIM
- LOGAM- NON- LOGAM
SEL DALAM KEADAAN NORMAL
PRODUKSI PRO-OKSIDAN SEIMBANG DENGAN ANTI-OKSIDAN
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PRO-OKSIDAN ANTI-OKSIDAN
RADIKAL BEBAS NON RADIKAL
ENZIM
NON-ENZIM
- LOGAM- NON- LOGAM
SEL DALAM KEADAAN STRES OKSIDATIF
PRODUKSI PRO-OKSIDAN LEBIH BANYAK DARI ANTI-OKSIDAN
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REACTIVE SPECIES AND RADICALS INVOLVED
IN OXIDATIVE STRESS FERRYL ION SUPEROXIDE ANION : .02
-
HYDROGEN PEROXIDE : H202
HYDROXYL RADICAL :
.
0H PEROXINITRITE (0N00-)
SINGLET OXYGEN : 102
OXYL (RO.) AND PEROXYL (ROO.) RADICALS
OZONE (O3)
PURINE AND PYRIMIDINE RADICAL CATIONS
(Thomas, 2006)
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PEMBENTUKAN ANION SUPEROKSIDA TERJADI DI:
MITOKONDRIA
MEMBRAN RETIKULUM ENDOPLASMIK
MEMBRAN PLASMA LEKOSIT DAN SELFAGOSIT
SITOPLASMA
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ANION SUPEROKSIDA TERJADI AKIBAT OTO-
OKSIDASI:
FLAVIN
HEMOGLOBIN
KATEKOLAMIN
TETRAHIDROPTERIDIN SENYAWA NITRO-AROMATIK DAN NITRO-
HIDROKSILAMIN
THIOLS
MELANIN
Cu (II) dan Fe(II) KOMPLEKS
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PEMBENTUKAN ANION SUPEROKSIDA
SECARA ENZIMATIK: TRANSPORT ELEKTRON MIKROSOMAL
RANTAI PERNAPASAN MITOKONDRIA
LEKOSIT DAN MAKROFAG SAAT MEMBUNUH
BAKTERI
OKSIDASE
FERREDOXINS
METABOLISME ZAT BESI
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PEMBENTUKAN HIDROGEN PEROKSIDA
SUPEROXIDE DISMUTASE
ACYL-CoA OXIDASE
GLYCOLATE/URATE OXIDASE XANTHIN OXIDASE
GLUTATHIONE OXIDASE
MONOAMINE OXIDASE
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PEMBENTUKAN RADIKAL HIDROKSIL DARI ANION SUPEROKSIDA
REAKSI HABER-WEISS.02
-+ H202 02 + H0- + H0.
REAKSI HABER-WEISS YANG DIKATALISIR ZAT BESI
FeIII+ .02- FeII + 02
FeII + H2
02
FeIII + H0- + H0.
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PEMBENTUKAN RADIKAL BEBAS DARI ANION SUPEROKSIDA
RS.
02.-
H02.
H+
H202 + 02
0H. + 0H-
Fe2+
R.
R02.
R02H
0H-+ R0.
Fe2+
RH
RH02
SUPEROXIDE
HYDROPEROXY
HYDROXYL
CARBON
PEROXY
ALKOXY
(Wil lson, 1993)
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MECHANISM OF OXIDATIVE CELL DAMAGE
OXIDATION OF INTRACELLULAR THIOLS AND PYRIDINENUCLEOTIDES
IMPAIRMENT OF SIGNAL TRANDUCTION AND IONHOMEOSTATIS
MODIFICATION OF CYTOSCELETAL ORGANIZATION INHIBITION OF GLYCOLISIS
INFLICTION OF DNA DAMAGE
COLLAPSE OF THE MITOCHONDRIAL POTENTIAL
ATP DEPLETION
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ACTIVE OXYGEN SPECIES
OXIDATION OF CELLULAR THIOLS
INHIBITION OF Ca2+ TRANSLOCASE
SUSTAINED (Ca2+) ELEVATION
ACTIVATION OF Ca2+ DEPENDENT
CATABOLIC PROCESSES
DNA PROTEIN DISRUPTION OF
DEGRADATION DEGRADATION CYTOSKELETON
LOSS OF
MEMBRANE PHOSPHOLIPID
INTEGRITY DEGRADATION
CELL DEATH
(Orrenius, 1993)
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PENGARUH OKSIDAN TERHADAP
MAKROMOLEKUL
KARBOHIDRAT
ASAM NUKLEAT
PROTEIN LIPID
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PENGARUH RADIKAL HIDROKSIL TERHADAP
KARBOHIDRAT
MENGAMBIL SATU ATOM HIDROGEN DARI
ATOM KARBON MEMBENTUK CARBON
CENTERED RADICAL DAN MEMUTUS RANTAI
KAROBHIDRAT, MISALNYA PADA MOLEKULASAM HIALURONAT
AKIBATNYA MENGURANGI CAIRAN SYNOVIA
PADA SENDI YANG SAKIT
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PENGARUH RADIKAL HIDROKSILTERHADAPASAM NUKLEAT
DAPAT MENGENAI MOLEKUL PENTOSANYA
JUGA DAPAT MENGENAI BASA PURINENYA
MENJADI 8-HYDROXY- GUANOSINE, THYMINE
GLYCOL DAN 5-HYDROXYMETHYL URACIL
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PENGARUH STRES OKSIDATIF TERHADAP
PROTEIN
RADIKAL YANG REAKTIF DAPAT MEMECAH
PROTEIN PLASMA
RADIKAL BEBAS BEREAKSI DENGAN METAL
YANG ADA DI DALAM MOLEKUL PROTEIN
PROTEIN INTRASELULER DAPAT DI-OKSIDASI
OLEH OKSIDAN
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STEPS OF LIPID PEROXIDATION
(INITIATION) LIPID + R./OH. LIPID.
(PROPAGATION) LIPID. + O2 LIPID- OO.
LIPID-OO. + LIPID LIPID-OOH + LIPID.
(TERMINATION) LIPID. + LIPID. LIPID-LIPID
LIPID-OO.
+ LIPID.
LIPID-OO-LIPID
(SCAVENGING) LIPID. + VIT.E LIPID + VIT.E.
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ANTIOXIDANTS IN THE DEFENSE SYSTEM AGAINST FREE
RADICAL-INDUCED OXIDATIVE DAMAGE
PREVENTIVE ANTIOXIDANTS
RADICAL SCAVENGING ANTIOXIDANTS
REPAIR AND DE NOVO
(NIKI, 1993)
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H2O2, LOOH, METAL, SMOKING,ISCHEMIA,
LIGHT, DRUGS etc
SUPRESS RADICAL FORMATIONPreventing
antioxidants
FREE RADICALS
SUPRESS CHAIN INITIATION
TARGET MOLECULES(LIPIDS,PROTEIN,SUGARS,DNA)
CHAIN OXIDATION
BREAK CHAIN PROPAGATION
Radical scavenging
antioxidants
DAMAGE
DISEASES, CANCER, AGEING
Repair and
de novo
(Niki , 1993)
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Preventive antioxidants:Enzymes which reduce
hydro-peroxides and hydrogen peroxide
GLUTATHIONE PEROXIDASE
GLUTATHIONE-S-TRANSFERASE
PHOSPHOLIPID HYDROPEROXIDEGLUTATHIONE PEROXIDASE
PEROXIDASE
CATALASE
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Preventive antioxidants
Transferrin, ferritin, and lacotferrin sequester
iron
Ceruloplasmin sequesters copper
-carotene and lycopene quench singlet
oxygen and inhibit hydroperoxide formation
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RADICAL-SCAVENGING ANTIOXIDANTS
HYDROPHILIC:
Vitamin C, uric acid, bilirubin, albumin and
thiols
LIPOPHILLIC:
Vitamin E, ubiquinol, and carotenoids
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REPAIR AND DE NOVO ANTIOXIDANTS
PHOSPHOLIPASE A2
PROTEOLYTIC ENZYMES IN CYTOSOL AN
MITOCHONDRIA
DNA REPAIR SYSTEMS: glycosylases and
nucleases
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PERAN GLUTATHIONE SELAMA STRES OKSIDATIF
REDOX CYCLING
02.-
SUPEROXIDE ANION
H202 0H. + 0H-
Mn+ M(n+1)+
(2H+) (02)
SUPEROXIDE DISMUTASE
H20 +1/2 02
CATALASE
2H20
2 GSH
GSSG
NADP+
NADPH
+ H+
EKSKRESI
GLUTATHIONE
REDUCATSE
GLUTATHIONE
PEROXIDASE
GSSG TRANSLOCASE
(Orrenius, 1993)
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The Glutathione Antioxidant System
GLUTATHIONE
ASCORBATE
-TOCOPHEROL
OTHERS
REACTIVE
OXYGEN
SPECIES
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GLU-CySH
-GLU-CySH
(2) GSH
BREAKDOWN
GLYREDUCTASE
NADPH
GSSG
DEHDROASCOBATE ASCORBATE
H2O2
PEROXIDASE
H2O2
GLUTAREDOXIN
INTERACTIONS INVOLVING THE ANTIOXIDANT ACTIVITIES OF GLUTATHI ONEAND ASCORBATE (MARTENSSON, 1990)
BSO
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ROO. VIT.E DHA DHLA NAD+
ROOH Vitamin E Ascorbate Lipoate NADH
Free Radical
-LIPOIC ACID INCREASES THE EFFICIENCY OF THE VITAMIN C CYCLE
AND THEREBY ALSO ACTIVATES THE VITAMIN E CYCLE (PACKER,2004)
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CRITERIA FOR CONSIDERING IDEAL
ANTIOXIDANTS
SPECIFICITY OF FREE RADICAL QUENCHING
METAL CHELATING ACITIVITY
INTERACTION WITH OTHER ANTIOXIDANTS
EFFECTS ON GENE EXPRESSION ABSORPTION AND BIOAVAILABILITY
CONCENTRATION IN TISSUES, CELLS, AND EXTRACELLULAR
FLUID
LOCATION (IN AQUEOUS OR MEMBRANE DOMAINS OR INBOTH?)
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ALPHA LIPOIC ACID
READILY ABSORBED FROM THE DIET
RAPIDLY CONVERTED TO DHLA IN MANY TISSUES
EFFECTIVELY QUENCH A NUMBER OF FREE RADICALS BOTH IN LIPID AND
AQUEOUS DOMAIN
BOTH DHLA AND -LIPOIC ACID HAVE METAL CHELATING ACITIVITY DHLA ACTS SYNERGITISCILLAY WITH OTHER ANTIOXIDANTS
THEY MAY HAVE EFFECTS ON REGULATORY PROTEINS AND ON GENES
INVOLVED IN NORMAL GROWTH AND METABOLISM
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7/22/2019 Biological Antioxidants
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Dan adapun orang- orang yang takut
kepada kebesaran Tuhannya danmenahan diri dari keinginan hawa
nafsunya maka sesungguhnya surgalah
tempat tinggal(nya) (Qs; An-Naziat:40-41)
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Penghujung malam. Sang khalifah, Ali
bin Abi Thalib, berdiri di tengahmihrabny. Sendiri. Tangannya
menengadah ke langit. Air matanya
tumpah ruah. Lirih benar ketika
doanya memecah sunyi, Tuhan,
biarlah dunia ini hanya berada dalamgenggaman tanganku. Jangan biarkan
ia masuk kedalam hatiku.