Free Radicals and Reactive Oxygen Species Flashcards
What is a free radical?
A molecule of a molecular species that contains one or more unpaired electrons and is capable of independent existence
What are the characteristic features of free radicals?
Highly reactive
Very short half-life
Can generate new radicals by chain reaction
Cause damage to biomolecules, cells and tissues
What are reactive oxygen species?
Used to collectively represent highly reactive free radicals and non-free radicals molecules of the biological systems
What does the complete reduction of oxygen form?
Water
Describe the pathway of incomplete reduction of oxygen
Name some ROS of biological importance
Singlet oxygen (1O2)
Hydroperoxy radical (HOO–)
Lipid peroxide radical (ROO–)
Nitric oxide (NO–)
Peroxynitrite (ONOO–)
How may free radicals be generated in the body?
Due to normal biological processes or cellular metabolism
Due to environmental effects
Describe the methods by which free radicals may be generated by cellular metabolism
Leakage of electrons from the Electron Transport Chain
Phagocytosis by macrophages (as a part of bactericidal action)
Production of H2O2 or O2– by oxidase enzymes
Metal ions [Fe2+, Cu2+] induced oxidation
Synthesis of prostaglandins, nitric oxide
Reactions in Peroxisomes
Reactions of membrane lipid peroxidation
How may free radicals be generated by environmental effects?
Drug metabolism (paracetamol and cytochrome P450 related reactions)
Alcohol, promoting lipid peroxidation
Cigarette smoke contains free radicals, and trace metals that generate OH–
Due to damages caused by ionizing radiations (e.g. X-rays) on tissues
Photolysis of O2 by light
Photoexcitation of organic molecules
Why are free radicals harmful?
They are capable of damaging all types of biomolecules
They generate more free radicals by chain reactions
What effects do free radicals have on proteins?
May damage proteins (by fragmentation, cross-linking and aggregation) leading to loss of biological activity
What effects do free radicals have on lipids?
Polyunsaturated fatty acids (PUFA) are highly susceptible to damage by free radicals
What effects do free radicals have on nucleic acids?
May cause DNA strand to break and fragment leading to cytotoxicity and mutations
What effects do free radicals have on carbohydrates?
Oxidation of monosaccharides can produce H2O2
What effect does free radicals have on glycated proteins?
Increases the susceptibility of proteins to attack by free radicals
In diabetes mellitus protein glycation and associated free radical damage is related to health complications e.g. diabetic microangiopathy, diabetic nephropathy
Glycation of proteins refers to linkage of carbohydrates to proteins
What diseases are free radicals associated with?
Cardiovascular Diseases
Inflammatory Diseases
Respiratory Diseases
Parkinson’s Disease
Alzheimer’s Disease
Cancer
Diabetes
Cataracts
Male Infertility
Aging Process
Multiple Sclerosis
Liver Cirrhosis
Muscular Dystrophy
Toxemia of Pregnancy
How may free radicals cause cardiovascular diseases?
Oxidized low density lipoproteins (LDL) (formed by the action of free radicals) promote atherosclerosis and CVD
How may free radicals cause cancer?
Free radicals can damage DNA and cause carcinogenesis
How may free radicals cause inflammatory diseases?
Rheumatoid arthritis is a chronic inflammatory disease. Free radicals produced by neutrophils are the predominant causative agents
Other inflammatory disorders (chronic glomerulonephritis and ulcerative colitis) are also caused due to ROS induced damages on the extracellular components (e.g. collagen, hyaluronic acid)
How may free radicals cause respiratory diseases?
Direct exposure of lungs to 100% oxygen for a long period (more than 24 hrs) may destroy endothelium and cause lung edema, mediated by free radicals.
ROS also responsible for adult respiratory distress syndrome (ARDS).
The damages caused to lungs in the smokers are due to ROS.
How may free radicals cause respiratory diseases?
Direct exposure of lungs to 100% oxygen for a long period may destroy endothelium and cause lung edema
ROS also responsible for adult respiratory distress syndrome (ARDS)
The damages caused to lungs in the smokers are due to ROS
How may free radicals cause diabetes?
One of the causes is ROS induced destruction of islets of pancreas
How may free radicals cause male infertility?
Free radicals reduce sperm motility and viability
What can be used to assess oxidative stress and free radical damage to the body?
Estimation of serum malondialdehyde (MDA)
