Free Radicals and Antioxidants
Free Radicals and Antioxidants
Free Radicals, are molecules that contain one or more unpaired electrons, and are capable of independent existence.
Types of Free Radicals
O2 is required for many metabolic reactions, mainly in the release of energy, in these processes oxygen is converted to water, but if reduction is incomplete, series of reactive radicals or Reactive oxygen species (ROS) are formed like-
- O2- superoxide
- H2O2 hydrogen peroxide
- OH- hydroxyl, etc.
Characteristic features of free radicals:
- Highly reactive
- Very short life
- Can generate free radicals by chain reaction
- Cause damage to biomolecules, cells and tissues
Sources and generation of free radicals
Normal biological processes
- Respiratory chain
- By oxidase enzymes
- Lipid Peroxidation : Occurs in 3 stages- initiation, propogation and termination. Of all the products of lipid peroxidation, MDA ( Malondialdehyde) is used as biochemical marker for assessment of lipid peroxidation. It reacts with thiobarbituric acid and produces red coloured products namely thiobarbituric acid reactive substances (TBARS), which can be measured colorimetrically. This estimation of serum MDA used to asses oxidative stress, and free radical damage in the body.
- Oxidation of heme to bile pigments
- During Phagocytosis: Inflammatory cells esp. Macrophages produce superoxide by reaction catalysed by NADPH oxidase. Superoxide→ Peroxide→ Hypochlorous acid. Superoxide with Hypochlorous ions bring about bactericidal action. (beneficial effect of ROS)
RESPIRATORY BURST: While the bactericidal function of macrophages, a large amount of oxygen is consumed by them, this phenomenon is called respiratory burst.
Due to environmental effects
- Drug metabolism ( paracetamol, halothane, cytochrome P 450)
- Ionizing radiations
- Cigarette smoking
- Alcohol (promotes lipid peroxidation)
Harmful effects of ROS : key role in carcinogenesis, damage DNA, promote atherosclerosis, Inflammtaory diseases ( rheumatoid arthritis, chronic glomerulonephritis, ulcertaive colitis), destruction of islets of pancreas, and many more.
For more information on the harmful effects of free radical, click on the link.
Substance that delays or inhibits the oxidation of substrate. Scavengers of free radicals.
1. According to location
- Plasma : ß-carotene, ascorbic acid, uric acid, ceruloplasmin, trasferrin.
- Cell membrane : Vit E
- Intracellular : Superoxice dismutase, catalase, glutathione peroxidase
2. According to Nature and Action
- Enzymatic- Superoxide dismutase, catalse, glutathione peroxidase
- Non enzymatic- Nutrient ( carotenoids, Vit E, Vit C, Selenium) ; Metabolic ( glutatione, ceruloplasmin, transferrin, bilirubin, albumin, uric acid)
Antioxidant enzyme system
Superoxide dismutase: Converts superoxide to hydrogen peroxide and O2. This is the first line defense.
Catalase: Hydrogen peroxide produced by superoxide dismutase is metabolised by catalase.
Glutathione peroxidase: It detoxifies H2O2 to H2O, while reduced glutathione (G-SH) is converted to oxidized glutathione (GS-GS). Reduced glutathione can be regenerated by enzyme glutathione reductase utilizing NADPH. The hexose monophosphate shunt is major source of NADPH. Selenium is required for function of glutathione peroxidase, can be obtained from sea foods, organ meats, and whole grains.
Some Points to Remember
Ceruloplasmin is copper containing metabolic antioxidant, inhibits copper and iron dependent lipid peroxidation.
Transferrin (transport form of iron) binds to iron and prevents iron catalysed free radical formation.
Essentials of Biochemistry - Satynarayana 2nd edition.