Free Radicals
Free radicals are chemical compounds that have unpaired electrons in their outer shell.
Free radicals can be made via physiologic processes (ATP production) or via pathologic processes.
Physiologic free radical production
Oxidative phosphorylation results in the physiologic generation of free radicals.
This is due to cytochrome C oxidase complex transferring electrons to oxygen.
The partial reduction of oxygen yields superoxide hydrogen peroxide and hydroxyl radicals.
Pathologic free radical production
Pathologic generation of free radicals may be due to:
- Drugs (e.g. acetaminophen)
- Chemicals
- Inflammation (due to NADPH oxidase oxidative burst reaction)
- Metals (e.g. Fenton reaction: iron (Fe), copper (Cu))
- Ionizing radiation
NADPH oxidase creates superoxide ions during oxygen dependent killing by neutrophils.
The Fenton reaction results in the creation of hydroxide (OH–) and a hydroxyl radical (-OH) by a reaction between Iron (Fe2+) and hydrogen peroxide (H2O2).
Ionizing radiation can result in pathologic generation of free radicals.
Free radicals are eliminated by three major ways:
- Antioxidants
- Enzymes
- Metal carrier transport proteins
Antioxidants help eliminate free radicals.
Certain enzymes may help with removal free radicals which include:
- Superoxide dismutase (O2– (superoxide))
- Catalase (H2O2 (hydrogen peroxide))
- Glutathione peroxidase (OH– (hydroxyl))
Metal carrier transport proteins may also help clear free radicals which include:
- Transferrin
- Ceruloplasmin
Note that the OH– (hydroxyl) free radical is the most damaging.
Free Radical Injury
Carbon tetrachloride is used by the dry-cleaning industry.
Carbon tetrachloride as an organic solvent.
Carbon tetrachloride (CCl4) is converted to CClO3 radical by the P450 system of hepatocytes.
Carbon tetrachloride can result in injury of the rough endoplasmic reticulum, leading to impaired protein synthesis.
Carbon tetrachloride results in fatty change of the liver due to decreased liver production of lipoproteins.
Free radical injury may also be due to reperfusion injuries.
Reperfusion injuries are due to the return of blood to an ischemic site that results in the production of oxygen derived free radicals which damages the tissue even more.
