Question

Inhibitors of Oxidative Phosphorylation The following chemicals inhibit oxidative phosphorylation: Cyanide: Cyanide is a naturally occurring compound that binds to protein complex IV of the mitochondrial electron transport chain and prevents transfer of electrons from the protein. Metformin: At the cellular level, chemically synthesized metformin, a drug commonly prescribed for Type 2 diabetes, inhibits mitochondrial respiration by blocking complex I. Dinitrophenol: Dinitrophenol is a metabolic poison that can be sold legally as a pesticide. Although it is lethal to humans, it is also sold as an unregulated weight-loss product. This molecule can bind to H+ ions and then, because the molecule is nonpolar, it diffuses across cell membranes. oligomycin: This is an antibiotic that inhibits ATP synthase by blocking its proton channel. The proton channel is necessary for oxidative phosphorylation of ADP to ATP.

Answer 1

A. Cyanide binds to the a3 portion (complex IV) of cytochrome oxidase and prevents cells from using oxygen.

B. Metformin - Activation of these enzymes increases the NADH/NAD ratio and hence the flow of electrons through the respiratory chain, thus increasing ATP production. Metformin inhibits complex 1 and decreases ATP production. ... Metformin has been shown to protect primary cortical neurons and cardiomyocytes from apoptosis33, 34.

C. Dinitrophenol - DNP acts as a protonophore, allowing protons to leak across the inner mitochondrial membrane and thus bypass ATP synthase. This makes ATP energy production less efficient. In effect, part of the energy that is normally produced from cellular respiration is wasted as heat.

D. Oligomycin - The inhibition of ATP synthesis by oligomycin A will significantly reduce electron flow through the electron transport chain; however, electron flow is not stopped completely due to a process known as proton leak or mitochondrial uncoupling.

2. As cyanide binds to cytochrome then there is no pump of electrons to inter membrane space then there will be increase in pH of intermembrane space and pH gradient will decrease which will stop ATP synthesis.

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