Free Radical Cell Injury

Overview
  • Free Radicals are molecular species which possess a single, unpaired electron in their outer orbital. Such unpaired electrons are highly reactive and radical-containing molecules rapidly and non-specifically attack a wide variety of biological molecules, removing their electrons in a bid to find an electron pair. Sadly, while the attack satisfies the original molecule's hunger for an electron, the molecular victim is often itself turned into a free radical. This zombie-like, spreading pattern of free radicals can result in wide-spread derangement of cellular components. Consequently, free radicals are one of the most potent agents of cellular injury and are sadly generated by processes critical for cellular survival.
Causes
  • Cellular Respiration
    • Regulated transfer of free radicals is the basis of the Electron Transport Chain that powers Cellular Respiration. Although the free radicals generated during electron transport are tightly controlled, a small amount can escape and cause damage. Escape of free radicals is substantially enhanced when mitochondria are injured which occurs frequently following Metabolic Cell Injury.
  • Ionizing Radiation
    • Exposure of Ionizing Radiation causes the generation of a variety of free radical species. This occurs following radiation-induced splitting of molecules which often generates free radicals products.
  • Chemical Cell Injury
    • Metabolism of several exogenous chemicals can result in the generation of free radicals (See: Chemical Cell Injury).
Biochemical Effects
  • As described previously, free radicals non-specifically attack a wide variety of biological molecules and no class of molecules is immune. Attack by free radicals often results in derangement of the attacked molecule and thus its biological function can no longer be performed. Attack of lipids in the plasma membrane or mitochondrial membrane can derange their selective permeability (See: Cell Injury Biochemistry). Additionally, attack of proteins can destroy their enzymatic function which may be required to maintain plasma membrane permeability or mitochondrial function. Finally, free radicals can attack nucleic acids and thus induce pathways of apoptosis.
Protection Mechanisms
  • Overview
    • Given the potent injurious capacity of free radicals it is not surprising that all cells possess a variety of mechanisms to defuse these molecules.
  • Glutathione:
    • This small biological molecule can deliver an electron to free radicals and not itself become a radical, thus squelching the free radical chain.
  • Anti-radical Enzymes:
    • Superoxide Dismutase is an enzyme which can modify oxygen-based free radicals to generate hydrogen peroxide which can subsequently be split into oxygen and water by the enzyme Catalase. Together these two enzymes can defuse oxygen-based radicals.
  • Anti-oxident Molecules:
    • A variety of molecules exist which can deliver electrons to oxygen-based free radicals and not themselves become radicals, similar to Glutathione. Molecules with anti-oxidant properties include Vitamin A, Vitamin C, and Vitamin E.