Download - Antioxidant xenobiotic
-
8/13/2019 Antioxidant xenobiotic
1/40
Virhan Novianri
Ratnayani
Andi Noor Kholidha Sayrifin
-
8/13/2019 Antioxidant xenobiotic
2/40
-
8/13/2019 Antioxidant xenobiotic
3/40
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 ?
-
8/13/2019 Antioxidant xenobiotic
4/40
Struktur Atom
Atom:Unit terkecil dari suatu materi
Atoms terdiri dari
Nucleusbermuatan positif di inti atom Electronsbermuatan negatif mengelilingi inti
-
8/13/2019 Antioxidant xenobiotic
5/40
Oksidasi
molekul di dalam sel terdiri dari atom-atom
Selama reaksi metabolisme, elektron dapat
ditransfer.
-
8/13/2019 Antioxidant xenobiotic
6/40
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
-
8/13/2019 Antioxidant xenobiotic
7/40
Pembentukan Radikal Bebas
Figure 8.4
-
8/13/2019 Antioxidant xenobiotic
8/40
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
-
8/13/2019 Antioxidant xenobiotic
9/40
Peroksidasi lipid
-
8/13/2019 Antioxidant xenobiotic
10/40
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
-
8/13/2019 Antioxidant xenobiotic
11/40
Pertahanan tubuh dari radikal bebas
Tubuh memiliki beberapa mekanisme pertahanan
terhadap radikal bebas yang melibatkan antioksidan
endogen baik berupa molekul enzim maupun
nonenzim
-
8/13/2019 Antioxidant xenobiotic
12/40
-
8/13/2019 Antioxidant xenobiotic
13/40
-
8/13/2019 Antioxidant xenobiotic
14/40
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
-
8/13/2019 Antioxidant xenobiotic
15/40
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
-
8/13/2019 Antioxidant xenobiotic
16/40
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)
-
8/13/2019 Antioxidant xenobiotic
17/40
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
-
8/13/2019 Antioxidant xenobiotic
18/40
Enzymes defence mechanism
-
8/13/2019 Antioxidant xenobiotic
19/40
Pertahanan
Enzymatic antioxidants
Superoxide dismutase (SOD)
Catalase
Gluthathione peroxidase (GPx)
-
8/13/2019 Antioxidant xenobiotic
20/40
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).
-
8/13/2019 Antioxidant xenobiotic
21/40
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.
-
8/13/2019 Antioxidant xenobiotic
22/40
Functions of GSH-dependent Enzymes
L-OH
H2OGSSG NADPH
L-OOH
H2O2GSH NADP+
X.
GSX
X-Mercapturic Acid
GSH Px
GSH-TR
GSH--Rx
-
8/13/2019 Antioxidant xenobiotic
23/40
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
-
8/13/2019 Antioxidant xenobiotic
24/40
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)
-
8/13/2019 Antioxidant xenobiotic
25/40
Sintesis Gluthation
Protein
Methionine
CysteineGlutamate
-Glutamylcysteine
Glycine
-
8/13/2019 Antioxidant xenobiotic
26/40
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
-
8/13/2019 Antioxidant xenobiotic
27/40
Nutritional
antioxidant
Antioxidantnutrients
vitamin E, vitamin C,vitamin A, beta-
carotene
Phytochemicalsantioxidants fromplants
-
8/13/2019 Antioxidant xenobiotic
28/40
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
-
8/13/2019 Antioxidant xenobiotic
29/40
Aktifitas antioksidan dari tokoferol
LOO + TOH LOOH + TO
-
8/13/2019 Antioxidant xenobiotic
30/40
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
-
8/13/2019 Antioxidant xenobiotic
31/40
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
-
8/13/2019 Antioxidant xenobiotic
32/40
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
-
8/13/2019 Antioxidant xenobiotic
33/40
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
-
8/13/2019 Antioxidant xenobiotic
34/40
Carotenoids as a free radical scavenger
-
8/13/2019 Antioxidant xenobiotic
35/40
-
8/13/2019 Antioxidant xenobiotic
36/40
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)
-
8/13/2019 Antioxidant xenobiotic
37/40
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
-
8/13/2019 Antioxidant xenobiotic
38/40
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
-
8/13/2019 Antioxidant xenobiotic
39/40
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
-
8/13/2019 Antioxidant xenobiotic
40/40
Terima kasih