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    Stres Oksidatif: Andriani Dept. Biokimia FK Untan

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    Chandra
    This document discusses oxidative stress and reactive oxygen species. It contains the following key points: 1. Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules, including free radicals, that are produced naturally in cells and can damage biological molecules like lipids, proteins, and DNA. 2. Major sources of ROS in cells include enzymes like CoQ and oxidases, ionizing radiation, phagocytic cells, and xenobiotic metabolism. 3. Cells have antioxidant defenses like antioxidant enzymes and dietary antioxidants that neutralize ROS and prevent oxidative damage. 4. When an overproduction of ROS overwhelms antioxidant defenses, oxidative stress occurs, which can lead to cell damage if left unchecked.

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    Stres Oksidatif: Andriani Dept. Biokimia FK Untan

    Uploaded by

    Chandra
    12 views34 pages
    This document discusses oxidative stress and reactive oxygen species. It contains the following key points: 1. Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules, including free radicals, that are produced naturally in cells and can damage biological molecules like lipids, proteins, and DNA. 2. Major sources of ROS in cells include enzymes like CoQ and oxidases, ionizing radiation, phagocytic cells, and xenobiotic metabolism. 3. Cells have antioxidant defenses like antioxidant enzymes and dietary antioxidants that neutralize ROS and prevent oxidative damage. 4. When an overproduction of ROS overwhelms antioxidant defenses, oxidative stress occurs, which can lead to cell damage if left unchecked.

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    This document discusses oxidative stress and reactive oxygen species. It contains the following key points: 1. Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules, including free radicals, that are produced naturally in cells and can damage biological molecules like lipids, proteins, and DNA. 2. Major sources of ROS in cells include enzymes like CoQ and oxidases, ionizing radiation, phagocytic cells, and xenobiotic metabolism. 3. Cells have antioxidant defenses like antioxidant enzymes and dietary antioxidants that neutralize ROS and prevent oxidative damage. 4. When an overproduction of ROS overwhelms antioxidant defenses, oxidative stress occurs, which can lead to cell damage if left unchecked.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    12 views34 pages

    Stres Oksidatif: Andriani Dept. Biokimia FK Untan

    Uploaded by

    Chandra
    This document discusses oxidative stress and reactive oxygen species. It contains the following key points: 1. Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules, including free radicals, that are produced naturally in cells and can damage biological molecules like lipids, proteins, and DNA. 2. Major sources of ROS in cells include enzymes like CoQ and oxidases, ionizing radiation, phagocytic cells, and xenobiotic metabolism. 3. Cells have antioxidant defenses like antioxidant enzymes and dietary antioxidants that neutralize ROS and prevent oxidative damage. 4. When an overproduction of ROS overwhelms antioxidant defenses, oxidative stress occurs, which can lead to cell damage if left unchecked.

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    © All Rights Reserved
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    Download as pptx, pdf, or txt
    of 34

    STRES OKSIDATIF

    Andriani
    Dept. Biokimia
    FK UNTAN

    FREE RADICAL
    is a molecule that has a single unpaired
    electron in an orbital, radical capable of
    independence existance
    Radicals are highly reactive and initiate
    chain reactions by extracting an electron
    from a neighboring molecule to complete
    their own orbitals.
    The oxygen atom is a biradical, which
    means it has two single electrons in
    different orbitals.

    O2 is capable of
    accepting a total of
    four electrons, which
    reduces it to water

    Characteristics of Reactive
    Oxygen Species (ROS)
    Reactive oxygen species (ROS) are
    oxygen-containing compounds that are
    highly reactive free radicals, or
    compounds readily converted to these
    oxygen free radicals in the cell
    Reactive free radicals extract electrons
    (usually as hydrogen atoms) from other
    compounds to complete their own
    orbitals, thereby initiating free radical
    chain reactions

    Major Sources of Primary Reactive Oxygen


    Species in the Cell
    1. CoQ GENERATES SUPEROXIDE

    2. OKSIDASE , OKSIGENASE,
    PEROKSIDASE

    3. IONIZING RADIATION

    4. synthesized by dedicated enzymes


    in phagocytic cells likeneutrophils
    andmacrophages
    NADPH oxidase(in both type of
    phagocytes)
    myeloperoxidase(in neutrophils only)

    5. Phase 2 Xenobiotic Metabolism

    OXYGEN RADICAL REACTIONS WITH CELLULAR


    COMPONENTS
    Membrane Attack: Formation of Lipid and Lipid
    Peroxy Radicals

    B. Protein and Peptides


    the amino acids proline, histidine,
    arginine, cysteine, and methionine
    are particularity susceptible to
    hydroxyl radical attack and oxidative
    damage
    C. DNA

    OXYGEN RADICAL REACTIONS WITH CELLULAR


    COMPONENTS

    CELLULAR DEFENSES AGAINST


    OXYGEN TOXICITY
    antioxidant defense enzymes : react with
    ROS and cellular products of free radical
    chain reactions to convert them to nontoxic
    products
    dietary : vitamine E, flavonoid
    endogenous antioxidants (free radical
    scavengers),
    Cellular compartmentation,
    metal sequestration
    repair of damaged cellular components.

    ANTIOXIDANT SCAVENGING
    ENZYMES

    NONENZYMATIC
    ANTIOXIDANT

    OXIDATIVE STRESS

    METABOLISME
    XENOBIOTIK
    Andriani
    Departemen Biokimia dan
    Biologi Molekuler FK UNTAN

    XENOBIOTIK
    = senyawa bukan makanan, asing
    obat, food additive, polutan, bahan
    industri
    Masuk melalui oral, injeksi, inhalasi,
    kulit
    Contoh :PCB, insektisida, kosmetik, dll
    Setiap hari manusia terpajan
    xenobiotik berbahaya utk kesh
    Dalam tubuh xenobiotik mengalami
    reaksi biotransformasi

    TUJUAN
    Membuat senyawa tersebut lipofilik
    menjadi lebih polar mudah
    diekskresi
    Dahulu disebut reaksi detoksifikasi
    kurang tepat, lebih tepat
    biotransformasi
    Ada senyawa yg semula lipofilik
    hidrofilik, menjadi lebih toksik

    Contoh reaksi detoksifikasi :


    detoksifikasi indol
    Indol hasil pembusukan triptofan
    oleh mikroorganisme usus besar
    toksik diresorbsi melalui usus
    halus dibawa ke hati indoksil sulfat
    (= indikan) lebih larut ekskresi
    melalui ginjal (dalam keadaan tidak
    toksik)

    Hati, ginjal. Usus tempat utama reaksi


    biotransformasi
    Sebagian besar senyawa xenobiotik
    mengandung cincin aromatik bersifar
    hidrofobik dpt diakumulasi dalam jaringan
    adiposa, bila tidak dapat diolah dan
    diekskresi oleh hati n ginjal mll rx
    biotransformasi
    Rx biotransformasi melibatkan segolongan
    enzim dng spektrum yg sangat luas

    Contoh enzim dlm Rx


    Biotransformasi
    - Mixed- function
    oxidase
    - Flavin
    monooksigenas
    e
    - Dehidrogenase
    - Reduktase
    - Glutathion
    S
    transferase
    - UDP glukoronil
    transferase

    Asetil transferase
    Amidase-esterase
    Metil transferase
    Sulfotransferase
    UDP
    glukosil
    transferase

    DUA TAHAP REAKSI


    Reaksi fase I
    - Senyawa xenobiotk menerima gugus
    fungsional menjadi lebih polar
    - Reaksi hidroksilasi dikatalisis oleh
    monooksigenase / sitokrom P450
    - Reaksi reduksi
    - Reaksi hidrolisis
    - Jga deaminasi, dehaogenasi, desulfurasi,
    epoksidasi, peroksigenasi

    Reaksi fase I mempersiapkan


    senyawa xenobiotik untuk bereaksi
    dengan substrat endogen pada
    reaksi fase II

    Reaksi fase II
    Senyawa yang telah mengalami reaksi
    fase I dikonjugasi dng seny. Endogen
    - Asam glukoronat
    - Sulfat
    - Asetat
    - Glutathion
    - Asam amino
    - Gugus metil

    absorbs
    i

    Biotransformasi
    Fase I

    Fase II

    ekskre
    si

    Metaboli
    t Polar
    Metabolit
    aktif

    konjugasi

    xx
    Metabolit
    inaktif
    Lipofilik

    Konjugasi
    hidrofilik

    Hasil reaksi fase I dan II


    Peningkatan polaritas
    Sangat larut dalam air
    Mudah diekskresi

    Kecepatan metabolisme xenobiotik


    dapat emngalami perubahan karena
    induksi atau inhibisi metabolisme
    bermanifestasi terhadap
    Perubahan profil kinetik obat
    Interaksi antar xenobioti
    Efek samping obat

    Efek Toksik xenobiotik


    Kematian sel > metabolit berikatan dng
    mekromolekul (prot., lipid, DNA) secara kovalen
    > mempengaruhi fungsi sel > kematian sel
    Perubahan antigenisitas protein sel > metabolit
    bereaksi dengan protein perubahan
    antigenisitas, berperan sebagai hapten
    merangsang pembentukan antibodi reaksi AgAb merusak sel
    Mutasi keganasan > karena berikatan dengan
    DNA/RNA secara kovalen

    Beberapa faktor yang mempengaruhi


    efek toksis xenobiotik

    Sistem enzim
    Status sistem imun
    Gizi
    Genetik lingkungan
    Sex
    Umur

    TERIMA KASIH

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