24 Superoxide - Free Radicals - Oxidative Stress

24 Superoxide - Free Radicals - Oxidative Stress -...

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Unformatted text preview: Superoxide, Free Radicals and Oxidative Stress HNFE 3025 Fall 2009 • Electron transfer through the complexes of the electron transport chain to oxygen leads to proton pumping from the mitochondrial matrix to the inner mitochondrial membrane space. – Creates an electrochemical gradient • Coupled oxidative phosphorylation is the reverse flow of these protons through ATP synthase back into the mitochondrial matrix to produce ATP. • If protons return to the matrix without passing through the ATP synthase or are used for other transport functions, they are not coupled to ATP synthesis. Coupled and Uncoupled Oxidative Phosphorylation 2 • Slipping – When protonmotive force is high, there can be incomplete coupling of proton pumping to electron transfer at sites I, III and IV. – Electrons are transferred through complexes but less protons are pumped across mitochondrial membrane. – This can lead to lower P/O ratios. • Leaking – Observed in isolated mitochondria – Can lead to a ‘futile cycle’ of proton pumping and leaking back, uncoupled to ATP synthesis. – Can average ~20% of electron transfer across species. • In BAT it is ~100% SLIPS & LEAKS 3 Are There Any Leaks or Slips? 4 • When slipping or leaking occurs this should result in increased O 2 consumption – Why? • Slips and leaks are difficult to measure because of methods of mitochondrial isolation • Evidence would suggest that slipping is insignificant. • Leaking without the use of uncoupling proteins most likely due to damaged mitochondria as a result of isolation procedures • Leaking with uncoupling proteins is real and relevant. Physiological relevance of slips and leaks? 5 OXIDATIVE STRESS AND FREE RADICAL PRODUCTION Reactive Oxygen Species (ROS) Reactive Oxygen and Nitrogen Species (RONS) 6 • ROS/RONS have a major role in: – Aging – Cancers – Cardiovascular disease – Cataracts – Inflammation – Alzheimer’s and brain degeneration – Cellular damage to phospholipids, proteins, RNA and DNA – Membrane damage Reactive Oxygen Species (ROS) Reactive Oxygen and Nitrogen Species (RONS) 7 •...
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This note was uploaded on 03/23/2010 for the course HNFE 3025 taught by Professor Mwhulver during the Spring '10 term at Virginia Tech.

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24 Superoxide - Free Radicals - Oxidative Stress -...

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