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Superoxide dismutase
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Catalyses 2O2- + 2H+ -> H2O2 + O2 - first line of defense against free radicals
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Fenton Reaction
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H2O2 converts to OH- and ·OH in the presence of Fe2+
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Haber Weiss Reaction
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Hydrogen Peroxide and superoxide react to form O2 water and peroxyl radical. Catalysed by Fe2+
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CoQ (Coenzyme Q10)
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Part of the electron transport chain in the mitochondria, it is a source of ROS when it sometimes loses it electron to a molecule of dioxygen -> superoxide
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Malondialdehyde
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3C, =O on either end. Forms when lipids are attacked by free radicals. Water soluble and a blood marker for free radical damage.
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Cytochrome P450
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Class of enzymes found in the liver which metabolise certain organic compounds, e.g. drugs, alcohol. May release free radicals, particularly when metabolising certain substances for which there is not an onward pathway, => intermediate products are released. Example is metabolism of CCl4 (used in dry-cleaning industry). First step oxidises it, producing CCl3· and Cl. There is no onward pathway, so the reaction products are released and may cause damage.
In the presence of suitable substrates, these enzymes are induced (upregulated) |
What happens when membranes are damaged by free radicals?
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Lose active transportMembrane proteins may become cross-linked
Influx of Ca2+, Na+ -> Influx of H2O -> cell swelling / lysis |
Which amino acids are most susceptible by free radical injury?
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Lysine, Histidine, proline, arginine, methionine. Cysteine and methionine are sulphur-containing
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Some diseases associated with free radical injury?
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Neurodegenerative disorders, e.g. PDDown's SyndromeRheumatoid arthritisReperfusion injuryDMDAlcohol-induced liver diseaseMS
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NADPH Oxidase
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Catalyses first reaction of the respiratory burst (dioxide --> Superoxide) by oxidising NADPH. Enzyme is membrane bound in phagocytic cells
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Myeloperoxidase
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Secreted into phagolysosomes during respiratory burst. Heme containing - gives pus a green colour. Catalyses H2O2 -> HOCl
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Inducible nitric oxide synthase (iNOS)
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Catalyses the production of NO to be released into phagolysosome during respiratory burst. NO may go on to combine with superoxide to produce ONOO- (peroxynitrate) which may then produce RNOS.
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Catalase
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Catalyses 2H2O2 -> 2H2O + O2
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Flavonoids
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Found in green tea, red wine, chocolate, etc. Antioxidant protection is unclear - chelate Fe + Cu, Inhibit superoxide producing enzymes, free radical scavengers?
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Features of Vitamin E as an anti-oxidant (4 points)
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- alpha tocopherol - lipid soluble, stays in membrane - donates electron to radical, e.g. LOO· ->forms tocopheryl radical - radical form tends to DONATE SECOND ELECTRON, thereby stopping another radical chain, rather than seeking to oxidise something else.
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