A Free Radical Bestiary

By now you're probably getting the idea. After brain ischemia, oxidative stress leads to a virtual smorgasbord of toxic species that overrun your neurons like so many Visigoths.

 

Oxidant

Description

•O2-, superoxide anion

One-electron reduction state of O2, formed in many autoxidation reactions and by the electron transport chain. Rather unreactive but can release Fe2+ from iron-sulphur proteins and ferritin. Undergoes dismutation to form H2O2 spontaneously or by enzymatic catalysis and is a precursor for metal-catalyzed •OH formation.

H2O2, hydrogen peroxide

Two-electron reduction state, formed by dismutation of •O2- or by direct reduction of O2. Lipid soluble and thus able to diffuse across membranes.

•OH, hydroxyl radical

Three-electron reduction state, formed by Fenton reaction and decomposition of peroxynitrite. Extremely reactive, will attack most cellular components

ROOH, organic hydroperoxide

Formed by radical reactions with cellular components such as lipids and nucleobases.

RO•, alkoxy and ROO•, peroxy radicals

Oxygen centred organic radicals. Lipid forms participate in lipid peroxidation reactions. Produced in the presence of oxygen by radical addition to double bonds or hydrogen abstraction.

HOCl, hypochlorous acid

Formed from H2O2 by myeloperoxidase. Lipid soluble and highly reactive. Will readily oxidize protein constituents, including thiol groups, amino groups and methionine.

OONO-, peroxynitrite

Formed in a rapid reaction between •O2- and NO•. Lipid soluble and similar in reactivity to hypochlorous acid. Protonation forms peroxynitrous acid, which can undergo homolytic cleavage to form hydroxyl radical and nitrogen dioxide.

Table: A free radical bestiary. (Table adapted from.[6][7][8])

 

This would be a big hairy mess in any cell, but the brain is especially vulnerable for the following reasons:

  1. lots of polyunsaturated fatty acid, which is prime fuel for free radical reactions;
  2. relatively deficient antioxidant defense;
  3. high rate of O2 utilization, and
  4. high content of transition metals like copper and iron to catalyze the Fenton reaction and promote formation of hydroxyl radicals.
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