Question

1. DNP (dinitrophenol) is an uncoupler, a toxin which creates holes in the inner mitochondrial membrane. How would this molecule affect metabolism in a cell?

2. Many people die each year from ingesting automotive antifreeze, which contains ethylene glycol. In the body, alcohol dehydrogenase converts the ethylene glycol into

oxalic acid which crystalizes and severely damages the kidneys. Ethanol is given to patients with antifreeze poisoning. What function do you think ethanol might have in the

reaction?

3. Sickle-cell anemia is caused by a point mutation in the substitution of valine by glutamic acid. If valine is replaced instead by leucine, normal hemoglobin structure is preserved. Explain this observation.

Answer 1

1.)DNP is a protonophore that has the ability to leak protons across the inner mitochondrial membrane and allowing the bypass of ATP synthase. In living cells, DNP acts as a proton ionophore, an agent that can shuttle protons (hydrogen cations) across biological membranes. It dissipates the proton gradient across mitochondria and chloroplast membranes, collapsing the proton motive force that the cell uses to produce most of its ATP chemical energy.

2) Antifreeze is a liquid that prevents the radiator in cars from freezing or overheating. It’s also known as engine coolant. Although water-based, antifreeze also contains liquid alcohols like ethylene glycol, propylene glycol, and methanol.

Ethanol and fomepizole are thought to act as inhibitors of alcohol dehydrogenase and therefore prevent the formation of acidic ethylene glycol metabolites.Ethanol as an antidote, competitively blocks the formation of toxic metabolites in toxic alcohol ingestions by having a higher affinity for the enzyme Alcohol Dehydrogenase (ADH).

3)As Valine is an aliphatic,hydrophobic, amino acid, it prefers substitution with other amino acids of the same type. The change from valine to leucine is from a hydrophobic amino acid to a similar hydrophobic acid and so this will have little change on the folding - not because they are hydrophobic but because they have also similarities in their structure. Therefore, if valine is replaced by leucine, normal haemoglobin structure is preserved.