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What is Uncoupler of oxidative phosphorylation is and explain in detail?
Mechanism of Action of DNP as uncoupler Dinitrophenol (DNP) a potent uncoupler is amphipathic and increase the permeability of the lipoid inner mitochondrial membrane to protons (H+), thus reducing the electrochemical potential and sho-circuiting the ATP synthase. In this way, oxidation can proceed without phosphorylation. Note: DNP was used for weight loss. But it was discontinued due to hypehermia and other side effects Inhibitors of ETC Site-I (Complex-I) * Rotenone: A fish poison and also insecticide. Inhibits transfer of electrons through complex-I-NADH-Q-reductase. * Amobarbital (Amytal) and Secobarbital: Inhibits electron transfer through NADH-Q reductase. * Piericidin A: An antibiotic. Blocks electron transfer by competing with CoQ. * Drugs: Chlorpromazine and hypotensive drug like guanethidine. Site-II (Complex III) * Antimycin A * BAL (dimercaprol) * Hypoglycaemic drugs: like Phenformin Site-III (Complex IV) * Cyanide Blocks electron transfer from cyt b to c1 Inhibits terminal * H2S * Azide transfer of electrons to molecular O2 * Co (Carbon monoxide): Inhibits Cyt. oxidase by combining with O2 binding site. It can be reversed by illumination with light. Complex II: Succinate dehydrogenase FAD * Carboxin * TTFA Specifically inhibit transfer of reducing equivalent from succinate dehydrogenase * Malonate: A competitive inhibitor of succinate dehydrogenase.Ref: MN Chatterjea Textbook of Medical Biochemistry, 8th edition, page no: 143 & 146