Home » Module 3: How Do Drugs Damage Neurons? It’s Radical! » Content Background: Cellular Targets for Oxidation by Oxygen Radicals

Content Background: Cellular Targets for Oxidation by Oxygen Radicals

Lipids, proteins and DNA are especially good targets for oxidation1 by oxygen radicals2. The location of lipids, proteins and DNA in the cell is crucial for cell function. For example, the lipids are found primarily in the plasma and nuclear membranes (and membranes of other cellular organelles), where they provide the structural matrix for the membrane. Proteins are found scattered about within the membrane and in the cytoplasm, where they perform numerous functions. They provide structural support within the cell, they function as enzymes3 and as receptors4, and they provide the machinery for cells to undergo respiration. DNA is found in the nucleus in the form of chromosomes and it provides the starting material to synthesize proteins.

Lipids, proteins and DNA all contain H atoms bound to C atoms. The H atoms are easily stolen by the hydroxyl radical (OH*). Hydroxyl radicals steal H atoms from the C chains of lipids and amino acids (the smallest unit that forms proteins), and from DNA bases. Many proteins also contain sulfur atoms bound to H atoms. When the OH*; steals an H from the sulfur groups (i.e. oxidizes the SH group), disulfide bonds (S-S) are formed. As the lipids, proteins, and DNA become oxidized by the OH*, they become radicals themselves (i.e., now they contain lone e- within their structure), creating a vicious cycle for radical generation (see Figure 7).

Figure 7 Watch the hydroxyl radicals (OH*) (orange circles) damage membrane lipids and proteins by removing H atoms from the lipid chains and from protein sulfhydryl groups (SH). The structure of both lipids and proteins is disturbed.


1 the donation of electrons to another atom often by removal of a H+ atom.
2 the reduction of oxygen by sequentially gaining electrons yields oxygen radicals such as the superoxide (O2*-) and the hydroxyl (OH*) radical. It is the OH* that damages lipids, proteins and DNA.
3 a protein that catalyzes the rate at which a reaction occurs. It binds to one of the reactants (a substrate) to cause a change in the reactant’s structure, facilitating the reaction.
4 a protein to which hormones, neurotransmitters and drugs bind. They are usually located on cell membranes and elicit a function once bound.