Harmful radical species in cells and natural antioxidants

While the high reactivity of the hydroxide radical is a beneficial trait in the atmosphere, it is a harmful trait when the same hydroxide radical is present in a living cell.  Hydroxide radical and other reactive oxygen species (ROS) such as superoxide (O₂^–) and peroxide (O₂ ^2-) are continuously produced as minor side-products in the reduction of O₂ to H₂O in respiration.

The ROS are highly reactive oxidizing agents, capable of inflicting damage to DNA, proteins, and the lipids of cell membranes – they are thought to play a major role in the natural aging process.  Hydroxide radical, for example, will initiate a radical chain reaction with the hydrocarbon part of an unsaturated  membrane lipid molecule that results in the formation of lipid hydroperoxide.

One important antioxidant that you are no doubt familiar with is ascorbic acid, or vitamin C.  It reacts with harmful radicals to produce the ascorbyl radical, which is significantly more stable than most other radical species due to resonance delocalization.  The end result of this first step is that a very reactive, potentially harmful radical (X•) has been ‘quenched’, and replaced by a much less reactive (and thus less harmful) ascorbyl radical.is thus potentially able to scavenge two harmful radical species.

Dehydroascorbate is subsequently either broken down and excreted, or else recycled (reduced) back to ascorbate.  This can happen either in a direct, enzyme-free reaction with glutathione, or through the action of a specific glutathione/NADH-dependant reductase enzyme.  You were invited to propose a likely mechanism for the enzyme-free reaction in problem 16.14.