biological antioxidants

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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34/35

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)


35/35

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.

biological antioxidants

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