uncoupler - Inhibitors & Uncouplers Bryant Miles The...

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Inhibitors & Uncouplers Bryant Miles The electron transport chain was determined by studying the effects of particular inhibitors. Rotenone is a common insecticide that strongly inhibits the electron transport of complex I. Rotenone is a natural product obtained from the roots of several species of plants. Tribes in certain parts of the world beat the roots of trees along riverbanks to release rotenone into the water which paralyzes fish and makes them easy prey. Amytal is a barbiturate that inhibits the electron transport of complex I. Demerol is painkiller that also inhibits complex I. All three of these complex I inhibitors block the oxidation of the Fe-S clusters of complex I. 2-Thenoyltrifluoroacetone and carboxin specifically block electron transport in Complex II. Antimycin A 1 is an antibiotic that inhibits electron transfer in complex III by blocking the transfer of electrons between Cyt b H and coenzyme Q bound at the Q N site. O O O H C CH 2 CH 3 O H H H 3 CO OCH 3 Rotenone Inhibitors of Complex I N CH 3 O O C H 2 CH 3 Demerol N NO O O CH 2 C H 2 H 3 C H 2 C CH H 3 C CH 3 H H Amytal S C O C O CF 3 S O CH 3 C O H N 2-Thenoyltrifluoroacetone Carboxin Inhibitors of Complex II O CH 2 H 2 C CH 2 H 2 C CH 2 H 3 C C O N H O O 1 0 O H 3 C O CH 3 C O C H 2 CH CH 3 CH 3 OH NH HC O Antimycin A 1 Inhibitor of Complex III
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Cyanide, azide and carbon monoxide all inhibit electron transport in Complex IV. The all inhibit electron transfer by binding tightly with the iron coordinated in Cyt a 3 . Azide and cyanide bind to the iron when the iron is in the ferric state. Carbon Monoxide binds to the iron when it is in the ferrous state. Cyanide and azide are potent inhibitors at this site which accounts for there acute toxicity. Carbon monoxide is toxic due to its affinity for the heme iron of hemoglobin. Animals carry many molecules of hemoglobin, therefore it takes a large quantity of carbon monoxide to die from carbon monoxide poisoning. Animals have relatively few molecules of Cyt a 3 . Consequently an exposure to a small quantity of azide or cyanide can be lethal. The toxicity of cyanide is solely from its ability to arrest electron transport. To the left is the effect of inhibitors of electron transport in the presence of O 2 and an electron donor such as NADH. The electron carriers before the inhibited step become fully reduced ( blue ). The electron carriers after the block are completely oxidized ( red ). Inhibitors of ATP Synthase DCCD, shown to the left, forms covalent bonds to a glutamate residue of the c subunit of F 0 . When DCCD is covalently attached it blocks the proton channel, which causes the rotation and ATP synthesis to cease. Oligomycin binds directly to ATP synthase F 0 subunit and blocks the flow of protons through the channel.
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This note was uploaded on 04/11/2010 for the course BICH bich 411 taught by Professor Bryantmiles during the Spring '10 term at Texas A&M.

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uncoupler - Inhibitors & Uncouplers Bryant Miles The...

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