antioxidant xenobiotic

8/13/2019 Antioxidant xenobiotic

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Virhan Novianri

Ratnayani

Andi Noor Kholidha Sayrifin


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Definisi Antioxidant

Suatu senyawa yang dapat mencegah reaksi

oksidasi dari senyawa lain yang bersifat radikal

bebas di dalam tubuh yang dapat merusak

berbagai makromolekul di dalam sel.

Reaksi oksidasi ?

Radikal bebas ?


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Struktur Atom

Atom:Unit terkecil dari suatu materi

Atoms terdiri dari

Nucleusbermuatan positif di inti atom Electronsbermuatan negatif mengelilingi inti


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Oksidasi

molekul di dalam sel terdiri dari atom-atom

Selama reaksi metabolisme, elektron dapat

ditransfer.


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Radikal Bebas

Suatu atom yang kehilangan satu elektron danmenyisakan elektron tak berpasangan pada atomtersebut

Sangat reaktif dan dapat menyebabkan kerusakanmolekul di dalam sel melalui reaksi berantai


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Pembentukan Radikal Bebas

Figure 8.4


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Pembentukan Radikal Bebas

Sumber radikal bebas dari reaksi oksidasiRantai Respirasi

Polusi

UV dan RadiasiXenobitoik

Dapat menyebabkan kerusakan di dalam sel

terhadap Membran Sel

Low Density Lipoprotein (LDLs)

Proteins

DNA


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Peroksidasi lipid


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Kerusakan protein oleh ROS

Kerusakan DNA

Radikal hidroksil (semua jenis basa)

Singlet oxygen bereaksi hanya dengan guanine

Kondensasi MDA (dari aldehydes) dengan adenine,

guanine atau cytosine


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Pertahanan tubuh dari radikal bebas

Tubuh memiliki beberapa mekanisme pertahanan

terhadap radikal bebas yang melibatkan antioksidan

endogen baik berupa molekul enzim maupun

nonenzim


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Strategy of antioxidant defence

tujuan: menghilangkan oksigen atau mengurangi

konsentrasi oksigen lokal

menghilangkan ion logam yang mengkatalisis

pembentukan ROS

menghilangkan ROS (e.g., O2-, H2O2, OH)

memutuskan reaksi berantai yang disebabkanoleh radikal bebas

regenarasi antioksidan

menghambat aktivitas enzim pro-oksidan


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The key reactions of chain-breaking antioxidants

can be listed as:

LOO + AH LOOH + A LO + AH LOH + A

A + LOO Non-radical products

A + A Non-radical products

Primary antioxidants can become less active at highconcentration because of their tendency to act aschain-carriers and become prooxidants (Gordon 1990):

AH + O2 A + HOO

AH + LOOH A + LO + H2O2


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Endogenous Antioxidants

Bilirubin

Thiols, e.g., glutathione, lipoic acid, N-acetyl cysteine

NADPH and NADH

Ubiquinone (coenzyme Q10) Uric acid

Enzymes:copper/zinc and manganese-dependent superoxide

dismutase (SOD)iron-dependent catalaseselenium-dependent glutathione peroxidase

Dietary Antioxidants

Vitamin C

Vitamin E Beta carotene and other carotenoids and oxycarotenoids,

e.g., lycopene and lutein

Polyphenols, e.g., flavonoids, flavones, flavonols, and

proanthocyanidins

Metal Binding Proteins

Albumin (copper) Ceruloplasmin (copper)

Metallothionein (copper)

Ferritin (iron)

Myoglobin (iron)

Transferrin (iron)


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Ubiquinon

Coenzyme Q10 is a group of homologous quinones (Figure

7.1). Coenzyme Q10 (CoQ10) or ubiquinone is a benzoquine

with an isoprenoid side chain (Kagan et al.1996).

Antioxidant activity of ubiquinone

QH + ROO Q + ROOH

Recycling of other antioxidants by ubiquinone

QH + TO Q + TOH

Prooxidant activity of ubiquinone

SQ- + O2 + H+ Q + HOO


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Enzymes defence mechanism


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Pertahanan

Enzymatic antioxidants

Superoxide dismutase (SOD)

Catalase

Gluthathione peroxidase (GPx)


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Superoksida Dismutase

(EC 1.15.1.1, SOD)

2O2. -+ 2H+H2O2+ O2

Superoxide Dismutase (SOD)membersihkansuperoxide yang dihasilkan dari rantai transferelektron kemudian menghasilkan hidrogenperoksida MnSOD (mitochondria).

CuZn SOD (cytosol).


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Glutathione Peroxidase (GSH PX)

Membersihkan hydrogen peroxide (H2O2)

and beberapa peroksida lipid.

Membutuhkan glutathione (GSH) sebagai

substrat dan menghasilkan gluthation yang

teroksidasi sebagai produk.

Merupakan enzim sitosolik.


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Functions of GSH-dependent Enzymes

L-OH

H2OGSSG NADPH

L-OOH

H2O2GSH NADP+

X.

GSX

X-Mercapturic Acid

GSH Px

GSH-TR

GSH--Rx


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GLUTATHIONE (GSH, GSSG)

Terdapat di dalam sel mamalia (1-10 mmol/l)

Buffer redoks yang penting

2 GSHGSSG + 2e-+ 2H+Eliminasi ROS, stabilisasi bentuk senyawa yang

tereduksi ( gugus SH-, tocopheryl and regenerasi

ascorbate)Merupakan substratglutathione peroxidases


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tripeptide, g-glutamyl-cysteinyl-glycine

The sulfur atom of the cysteine moiety is the reactive site whichprovides electrons

GSH is stable because the gbond in glutamyl-cysteine (not the apeptide bond) is resistant to cellular peptidases

GSH is a substrate for two enzymes that are responsible fordetoxification and antioxidation.

Other physiological roles including cysteine storage and transport,prostaglandin metabolism, immune function, cell proliferation andredox balance

GLUTATHIONE (GSH, GSSG)


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Sintesis Gluthation

Protein

Methionine

CysteineGlutamate

-Glutamylcysteine

Glycine


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Enzim Catalase

Catalase

menghilangkan hydrogen peroxideyang dihasilkan di peroxisome.

2 H2

O2

2 H2

O + O2

Afinitas tinggi terhadap H2O2Peroxisomes hepatocytes mitochondria,

cytoplasm of erytrocytes

Membentuk tetramer dengan Fe, membutuhkanNADPH


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Nutritional

antioxidant

Antioxidantnutrients

vitamin E, vitamin C,vitamin A, beta-

carotene

Phytochemicalsantioxidants fromplants


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Vitamin EVitamin larut lemak

Terdiri dari

Tocotrienolbiologically inactive form

Tocopherolbiologically active form

Fungsi Berperan sebagai antioksidan

Memproteksi (PUFAs)

Memproteksi LDLs

sumber

Minyak nabati, kacang-kacangan, biji-bijian, gandum, kedelai

Sangat sedikit pada hewan

Defisiensi

erythrocyte hemolysis


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Aktifitas antioksidan dari tokoferol

LOO + TOH LOOH + TO


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Vitamin CAsupan yang direkomendasikan

90 mg/day for men; 75 mg/day for women Smokers need an extra 35 mg/day

Sumber Fresh fruits and vegetables

Heat destroys vitamin C

Cooking foods lowers their vitamin C content

fungsiAntioxidant, Synthesis of collagen, Mencegah penyakit kulit, Meningkatkan sistem

imun

Meningkatkan absorpsi Fe

Defisiensi:Scurvy:the most common vitamin C deficiency disease

Bleeding gums, loose teeth, weakness

Can occur after one month on a vitamin C-deficient diet


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Vitamin C

Kecendrungan mengalami autooksidasi

Asc2- + O2 Asc- + O2-

Menetralkan radikal bebas

AscH- + X Asc- + XH

Regenerasi dengan bantuan anitoksidan lain

AscH- + TO Asc- + TOH


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Ascorbate is able to reduce catalytic metals such as Fe3+

and Cu2+ to their more catalytically ctive valence stateFe2+ and Cu+.

In general low concentrations of ascorbate are required for

prooxidant conditions, while high concentration isneeded for antioxidant conditions.

In the presence of ascorbate, catalytic metals will initiate

radical chain oxidations, but when ascorbateconcentration is high these radical processes will be lesssignificant


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Beta-caroteneBeta-carotene is

In the class of chemicals called carotenoids

A provitamin: inactive precursors that must be converted to the activeform of a vitamin in the body

The precursor of retinol

Functions of beta-carotene

A weak antioxidant Effective against oxidation in cell membranes and LDLs

Carotenoids in general are known to

Enhance the immune system

Protect skin from damage by UV light

Protect eyes from damage

There are no known deficiency symptoms


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Carotenoids as a free radical scavenger


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Vitamin AVitamin larut lemak

Excess vitamin A is stored in the liver, adipose tissue, kidneys, and lungs/There are three active forms of Vitamin A Retinol, Retinal, Retinoic acid

Fungsi Essential to proper vision , Antioxidant, protecting LDL cholesterol, Cell

differentiation:the process by which cells mature and specialize, Spermproduction and fertilization, Bone growth

Sources of vitamin A Animal sources: liver, eggs, Plant sources such as the provitamin carotenoids

(dark green, orange, and deep yellow fruits and vegetables)

What if you consume too much vitamin A?

Vitamin A is highly toxic, especially from supplements Birth defects and permanent damage to the liver and eyes can result

What if you dont consume enough vitamin A? Night blindness is the most common disease of vitamin A deficiency

Irreversible blindness (xerophthalmia)


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SeleniumSelenium is a trace mineral found in a few amino acids in the body.

Functions of selenium

Antioxidant; part of the glutathione peroxidase enzyme system

Production of thyroxinea thyroid hormone

Recommended intake

55 mg/day for men and women

UL is 400 mg/day

Sources of selenium

Rich sources include organ meats, pork, seafood, nuts, wheat, rice

What if you consume too much selenium?

Selenium toxicity (brittle hair, nails, skin rashes) can result from supplements

What if you dont consume enough selenium?

Keshan disease:a form of heart disease

Kashin-Beck disease:an arthritis


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Mekanisme Perbaikan

Ketika pencegahan dan penghancuran radikal

bebas gagal, produk stres oksidatif akan

menumpuk di DNA, protein, dan lipid.

i) DNA repair

ii) degradasi protein yang rusak

iii) metabolisme hidroperoksida lipid yang

terbentuk selama peroksidasi lipid


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Penutup

Antioksidan berperan dalam menghentikan reaksiberantai di dalam makromolekul sel yang disebabkanoleh radikal bebas dengan berbagai mekanisme

Antioksidan dapat berasal dari dalam maupun dari luar

sel

Ketidakseimbangan antara jumlah antioksidan dankerusakan yang ditimbulkan radikal bebasmenyebabkan stres oksidatif

Asupan nutrisi yang mengandung antioksidandiperlukan untuk meningkatkan pertahanan tubuhterhadap serangan radikal bebas


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Terima kasih

antioxidant xenobiotic

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