Virhan Novianri Ratnayani Andi Noor Kholidha Sayrifin

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 ?

Struktur Atom
Atom: Unit terkecil dari suatu materi
Atoms terdiri dari
Nucleusbermuatan positif di inti atom Electronsbermuatan negatif mengelilingi inti

Oksidasi
molekul di dalam sel terdiri dari atom-atom Selama reaksi metabolisme, elektron dapat ditransfer.

Radikal Bebas
Suatu atom yang kehilangan satu elektron dan menyisakan elektron tak berpasangan pada atom tersebut
Sangat reaktif dan dapat menyebabkan kerusakan molekul di dalam sel melalui reaksi berantai

Pembentukan Radikal Bebas

Figure 8.4

Pembentukan Radikal Bebas

Sumber radikal bebas dari reaksi oksidasi Rantai Respirasi Polusi UV dan Radiasi Xenobitoik Dapat menyebabkan kerusakan di dalam sel terhadap
Membran Sel Low Density Lipoprotein (LDLs) Proteins DNA

Peroksidasi lipid

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

Pertahanan tubuh dari radikal bebas

Tubuh memiliki beberapa mekanisme pertahanan terhadap radikal bebas yang melibatkan antioksidan endogen baik berupa molekul enzim maupun nonenzim

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 disebabkan oleh radikal bebas regenarasi antioksidan menghambat aktivitas enzim pro-oksidan

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 high concentration because of their tendency to act as chain-carriers and become prooxidants (Gordon 1990): AH + O2 A + HOO AH + LOOH A + LO + H2O2

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 catalase selenium-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)

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

Enzymes defence mechanism

Pertahanan
Enzymatic antioxidants Superoxide dismutase (SOD)

Catalase
Gluthathione peroxidase (GPx)

Superoksida Dismutase
(EC 1.15.1.1, SOD) 2O2. - + 2H+ H2O2 + O2

Superoxide Dismutase (SOD) membersihkan superoxide yang dihasilkan dari rantai transfer elektron kemudian menghasilkan hidrogen peroksida
MnSOD (mitochondria). CuZn SOD (cytosol).

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.

Functions of GSH-dependent Enzymes

L-OH H2O
GSH Px

GSSG
GSH--Rx

NADPH

L-OOH H2O2

GSH
GSH-TR

NADP+

X.

GSX X-Mercapturic Acid

GLUTATHIONE (GSH, GSSG) Terdapat di dalam sel mamalia (1-10 mmol/l) Buffer redoks yang penting 2 GSH GSSG + 2e- + 2H+ Eliminasi ROS, stabilisasi bentuk senyawa yang tereduksi ( gugus SH-, tocopheryl and regenerasi ascorbate) Merupakan substrat glutathione peroxidases

GLUTATHIONE (GSH, GSSG)

tripeptide, g-glutamyl-cysteinyl-glycine

The sulfur atom of the cysteine moiety is the reactive site which provides electrons
GSH is stable because the g bond in glutamyl-cysteine (not the a peptide bond) is resistant to cellular peptidases GSH is a substrate for two enzymes that are responsible for detoxification and antioxidation. Other physiological roles including cysteine storage and transport, prostaglandin metabolism, immune function, cell proliferation and redox balance

Sintesis Gluthation
Protein
Methionine

Cysteine
Glutamate

g-Glutamylcysteine
Glycine

Enzim Catalase
Catalase menghilangkan hydrogen peroxide yang dihasilkan di peroxisome.

2 H2O2 2 H2O + O2
Afinitas tinggi terhadap H2O2 Peroxisomes hepatocytes mitochondria, cytoplasm of erytrocytes Membentuk tetramer dengan Fe, membutuhkan NADPH

Nutritional antioxidant
Antioxidant nutrients vitamin E, vitamin C, vitamin A, betacarotene Phytochemicals antioxidants from plants

Vitamin E
Vitamin 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

Aktifitas antioksidan dari tokoferol LOO + TOH LOOH + TO

Vitamin C
Asupan 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

fungsi
Antioxidant, 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

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

Ascorbate is able to reduce catalytic metals such as Fe3+ and Cu2+ to their more catalytically ctive valence state Fe2+ and Cu+. In general low concentrations of ascorbate are required for prooxidant conditions, while high concentration is needed for antioxidant conditions.
In the presence of ascorbate, catalytic metals will initiate radical chain oxidations, but when ascorbate concentration is high these radical processes will be less significant

Beta-carotene
Beta-carotene is
In the class of chemicals called carotenoids A provitamin: inactive precursors that must be converted to the active form 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

Carotenoids as a free radical scavenger

Vitamin A
Vitamin 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, Sperm production 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)

Selenium
Selenium 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

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

Penutup
Antioksidan berperan dalam menghentikan reaksi berantai di dalam makromolekul sel yang disebabkan oleh radikal bebas dengan berbagai mekanisme Antioksidan dapat berasal dari dalam maupun dari luar sel Ketidakseimbangan antara jumlah antioksidan dan kerusakan yang ditimbulkan radikal bebas menyebabkan stres oksidatif Asupan nutrisi yang mengandung antioksidan diperlukan untuk meningkatkan pertahanan tubuh terhadap serangan radikal bebas

Terima kasih