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Lectures 25 Oxidative Phosphorylation-BW

Flow from fuel oxidation to o2 unless atp needs to be

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Unformatted text preview: be synthesized/consumed. acculmlate and ADP accumlate - feedback and inhibit alpha ATP synthesis is ATP low TCA cycle - slow slow dependent on its rate of utilization.- dsowndownsynthesis. elctron down oxygen consumption -ATP ATP taransport chain coupled to s ynthesi - functon as a unit - when coupled. ATP Synthesis and Electron Flow Are Coupled Events 4/12/13 MCB 2000 Lecture 25 How Can ATP Synthesis Be Inhibited? how can you uncouple? - why would you want to do this? - know difference between respiratory inhibitor and uncoupled. - fuel ( glucose fatty acid) - increase consumption or decrease? inhibit drectly ATP synthase - will also inhiti elctron trasnport chain going to be linked. the uncoupler destruption of protein gradient. respiratory inhbitor - how and where tehy work. Inhibition of ETC at any point (respiratory inhibitors) Direct inhibition of ATP synthase Disruption of proton gradient across IMM (uncouplers) 4/12/13 MCB 2000 Lecture 25 Respiratory Inhibitors Cyanide, azide inhibit Complex IV by reacting with Fe3+ of heme a3 CO binds to Fe2+ of heme a3 4/12/13 MCB 2000 Lecture 25 Inhibitors ATP Synthase Oligomycin (antifungal agent) DCCD Consequence of inhibition: Electron transport chain also inhibited 4/12/13 MCB 2000 Lecture 25 Uncouplers Disrupt the Coupling of Electron Transport and ATP Synthase Uncouplers disrupt the tight coupling between electron transport and oxidative phosphorylation by dissipating the proton gradient . How do uncouplers do this? Uncouplers are hydrophobic molecules with a dissociable proton They shuttle back and forth across the membrane, carrying protons to dissipate the gradient 4/12/13 MCB 2000 Lecture 25 Structures of several uncouplers, molecules that dissipate the proton gradient across the inner mitochondrial membrane and thereby destroy the tight coupling between electron transport and the ATP synthase reaction. Herbicides Fungicides Chemical coupler. ring structure - hydroxyl group. two nitrogen groups. Diet drug - OTC - but taken off the market. body temperature incrases. - taking the c ompound everyday and your body temp 104. dont have as much energy. 4/12/13 MCB 2000 Lecture 25 When H+ enter by a path other than the ATP Synthase Ox/Phos becomes uncoupled pick up a proton in the inner membrane space where it is a higher proton - diffuse acoss the menbrane - into the matrix where there is a differnce in ph matrix around 8 and inner membrane is ph of 6. hydroxyl group pck off a proton and carries into the matrix the hydrogen ion enter the membrane by a mechanism - change in the proton motvie force. electron trasnport chain consuming oxygen and fuel - two events uncoupled. 4/12/13 MCB 2000 Lecture 25 Consequences of uncoupling Excessive oxygen consumption and utilization of substrate; electron transport still occurs but no proton gradient and no ATP formed Energy is dissipated as heat Energy loss as heat. 4/12/13 MCB 2000 Lecture 25 Physiological uncoupling. brown adipose tissue c ontrolling how we burn fuel. heat production in the body. Uncoupling Proteins 4/12/13 MCB 2000 Lecture 25 Consequences of uncoupling Uncoupling of oxidative phosphorylation can have important physiological benefits important for generating heat hibernating animals plants emerging from the snow in spring Thermogenin (UCP-1) in brown adipose tissue in infants Uncoupling protein 1 known as thermogenin - babies need to regulate body temp. keep infants warm - they ahve trouble maintaining body temp - they can through the uncoupling of protein 1. plants - melt away soild soil over the winter - anaimals use uncoupling - during hybernation during the winter. 4/12/13 MCB 2000 Lecture 25 INcrease brown adipose tissue means you burn c alories thorugh use of uncoupling of these proteins. try and help rate of metabolism 4/12/13 MCB 2000 Lecture 25...
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