In light of what you now know about cellular respiration, explain the mechanism

Question

In light of what you now know about cellular respiration, explain the mechanism of action of poisons such as carbon monoxide, arsenic and 2,4 dinitriphenol (DNP), in that order.

In your answer, YOU NEED TO INCLUDE THE FOLLOWING TERMS: proton gradient, chemiosmosis, electron transport chain, acetyl CoA and Krebs cycle and make sure to HIGHLIGHT OR UNDERLINE THESE throughout the text.
Do not exceed a ONE page length (double spaced, 12 point font) for your answer. Dedicate a parragraph to each inhibitor. Don't forget to include at least one reference per inhibitor (i.e. incorporated in your text).

Explanation / Answer

The compound 2,4-dinitrophenol (DNP) acts as a proton ionophore, that is, it binds protons on one side of a membrane, and being fat-soluble it drifts to the opposite side where it loses the protons. Actually, the associations/dissociations are random, but the probability of binding is greatest on the side of the membrane with greatest proton concentration, and least on the side with the lesser concentration. Thus, it is impossible to maintain a proton gradient with sufficient DNP in the system. DNP is known to have mixed actions, that is, it produces other effects in addition to uncoupling. DNP gradually inhibits electron transport itself as it is incorporated into mitochondrial membranes. The effects appear to depend on concentration of DNP and of mitochondria, and vary from one preparation to the next. Back in the 1930s DNP was touted as an effective diet pill. Indeed, the uncoupling of electron transport from ATP synthesis allows rapid oxidation of Krebs substrates, promoting the mobilization of carbohydrates and fats, since regulatory pathways are programmed to maintain concentrations of those substrates at set levels. Since the energy is lost as heat, biosynthesis is not promoted, and weight loss is dramatic. However, to quote Efraim Racker (A New Look at Mechanisms in Bioenergetics, Academic Press, 1976, p. 155), ..."the treatment eliminated not only the fat but also the patients,...This discouraged physicians for awhile..." It is not a good idea to mess with cellular metabolism. Carbonyl cyanide p-[rifluoromethoxyl]-phenyl-hydrozone (FCCP) This agent is, in fact, a pure uncoupler. It acts as an ionophore, completely dissipating the chemiosmotic gradient, leaving the electron transport system uninhibited. It is also expensive. Oligomycin Oligomycin, an antibiotic, acts by binding ATP synthase in such a way as to block the proton channel. That is the mechanism by which oligomycin inhibits oxidative phosphorylation. Experimentally, oligomycin has no effect on state IV respiration, that is, it has no direct effect on electron transport or the chemiosmotic gradient. On the other hand oligomycin prevents state III respiration completely. To draw the conclusion that an agent is an inhibitor of ATP synthase (inhibitor of oxidative phosphorylation), the above conditions must be demonstrated experimentally and unequivocally. It takes awhile for the effects of oligmycin to show up. Attempts to interrupt state III respiration by adding oligomycin may fail because of the delay.

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