Question

13. Write about inhibitors of oxidative phosphorylation

Answer 1

There are many inhibitors of oxidative phophorylation like
Rotenone inhibits Complex l- and helps natives of the Amazon rain forest catch fish. 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.

2-Thenoyltrifluoroacetone and carboxin specifically block soluble ubiquinone-deficient succinate: ubiquinone reductase transport in Complex II. Antimycin Alis an antibiotic produced by Streptomyces. Sp, that inhibits electron transfer in complex III by blocking the transfer of electrons between Cyt band coenzyme Q bound at the Q site. It is a most potent inhibitors of the mitochondrial respiratory chain. Cyanide, azide and CO inhibit Complex IV, binding tightly to the ferric form (Fe3+) of a

Cyanide and azide are potent inhibitors at this site which accounts for there acute toxicity Inhibitors of ATP Synthase DCCD, forms covalent bonds to a glutamate residue of the c subunit of FO. When DCCD is covalently attached it blocks the proton channel, which causes the rotation and ATP synthesis to cease. Oligomycin are macrolides created by Streptomyces binds directly to ATP synthase FO subunit and blocks the flow of protons through the channel.

H CH IC 0 H ON (CH),CHCH.CH CH, C00C,H, OCH Amytal (amobarbital) Demerol (meperdine) Rotenone 0 HC HO CH3 CH3 CH3 0 0 CH 0 OCCH,CH(CH) CNH ноо он H. он NHCHO 2. Thenoyltrifluoroacetone CH,CH CHS 0 Antimycin A od CNH -N-C=N H Н4С Oligomycin A Carboxin Dicyclohexylcarbodiimide (DCCD)

Proton gradient Cyanide Azide Carbon Complex Complex II Come Owl Upredstave NADH CUM OX rechte Kenne ATP Complex III 10, +24+ Succinate Thenyitni fluoreton NADH DCCD Olymycin Raten Perleidin Awal Mercurial Demerel Carbon Uncouplers 2.4 dinitrophenol Dieumarol FCCP

Uncouplers Uncouplers inhibit oxidative phosphorylation. • They'uncouple' the ETC from oxidative phosphorylation. Uncouplers are hydrophobic molecules with a dissociable proton The ETC remains intact and electrons are transferred to 02 to generate H20. All of the uncouplers will collapse the pH gradient by binding a proton on the acidic side of the membrane, diffusing through the inner mitochondrial membrane and releasing the proton on the membrane's alkaline side.

Dinitrophenol ON OH NO, Dicumarol oo o OH OH Carbonyl cyanide-p-trifluoro- methoxyphenyl hydrazone —best known as FCCP; for Fluoro Carbonyl Cyanide Phenylhydrazone CN F3C—0 CN

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