Free Radicals and Reactive Oxygen Species

Question 1

What is a free radical?

Answer 1

A molecule of a molecular species that contains one or more unpaired electrons and is capable of independent existence

Question 2

What are the characteristic features of free radicals?

Answer 2

Highly reactive
Very short half-life
Can generate new radicals by chain reaction
Cause damage to biomolecules, cells and tissues

Question 3

What are reactive oxygen species?

Answer 3

Used to collectively represent highly reactive free radicals and non-free radicals molecules of the biological systems

Question 4

What does the complete reduction of oxygen form?

Answer 4

Water

Question 5

Describe the pathway of incomplete reduction of oxygen

Answer 5

Question 6

Name some ROS of biological importance

Answer 6

Singlet oxygen (¹O₂)
Hydroperoxy radical (HOO^–)
Lipid peroxide radical (ROO^–)
Nitric oxide (NO^–)
Peroxynitrite (ONOO^–)

Question 7

How may free radicals be generated in the body?

Answer 7

Due to normal biological processes or cellular metabolism
Due to environmental effects

Question 8

Describe the methods by which free radicals may be generated by cellular metabolism

Answer 8

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

Question 9

How may free radicals be generated by environmental effects?

Answer 9

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

Question 10

Why are free radicals harmful?

Answer 10

They are capable of damaging all types of biomolecules
They generate more free radicals by chain reactions

Question 11

What effects do free radicals have on proteins?

Answer 11

May damage proteins (by fragmentation, cross-linking and aggregation) leading to loss of biological activity

Question 12

What effects do free radicals have on lipids?

Answer 12

Polyunsaturated fatty acids (PUFA) are highly susceptible to damage by free radicals

Question 13

What effects do free radicals have on nucleic acids?

Answer 13

May cause DNA strand to break and fragment leading to cytotoxicity and mutations

Question 14

What effects do free radicals have on carbohydrates?

Answer 14

Oxidation of monosaccharides can produce H₂O₂

Question 15

What effect does free radicals have on glycated proteins?

Answer 15

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

Question 16

What diseases are free radicals associated with?

Answer 16

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

Question 17

How may free radicals cause cardiovascular diseases?

Answer 17

Oxidized low density lipoproteins (LDL) (formed by the action of free radicals) promote atherosclerosis and CVD

Question 18

How may free radicals cause cancer?

Answer 18

Free radicals can damage DNA and cause carcinogenesis

Question 19

How may free radicals cause inflammatory diseases?

Answer 19

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)

Question 20

How may free radicals cause respiratory diseases?

Answer 20

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.

Question 21

How may free radicals cause respiratory diseases?

Answer 21

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

Question 22

How may free radicals cause diabetes?

Answer 22

One of the causes is ROS induced destruction of islets of pancreas

Question 23

How may free radicals cause male infertility?

Answer 23

Free radicals reduce sperm motility and viability

Question 24

What can be used to assess oxidative stress and free radical damage to the body?

Answer 24

Estimation of serum malondialdehyde (MDA)