Free Radicals

• Free radicals are highly reactive chemical species that possess an unpaired electron in their outermost electron shell.

• This unpaired electron makes them highly unstable and reactive, as they seek to pair up with another electron to achieve stability.

• Free radicals can be formed through various processes, including normal cellular metabolism, exposure to environmental factors such as radiation and pollutants, and as byproducts of chemical reactions in the body.

• The unpaired electron in a free radical gives it the ability to interact with other molecules in the body, leading to potentially damaging effects.

• Free radicals can react with important cellular components such as proteins, lipids, and DNA, causing oxidative stress and disrupting normal cellular function.

• Oxidative stress occurs when there is an imbalance between the production of free radicals and the body's antioxidant defenses, leading to an excess of free radicals.

• While free radicals are generally associated with negative effects on health, they also play essential roles in various biological processes.

• For instance, they are involved in the immune response to pathogens, cell signaling, and regulation of certain enzymes.

• However, when free radicals exceed the body's antioxidant capacity, they can cause significant damage to cells and tissues, contributing to the development of various diseases, including cancer, cardiovascular diseases, neurodegenerative disorders, and aging.

• To counteract the harmful effects of free radicals, the body has an elaborate antioxidant defense system.

• Antioxidants are molecules that can donate an electron to neutralize free radicals and reduce their reactivity.

• Antioxidants can be obtained from the diet, including vitamins (such as vitamins C and E), minerals (such as selenium and zinc), and phytochemicals (found in fruits, vegetables, and other plant-based foods).

• The body also produces its own antioxidants, such as glutathione and enzymes like superoxide dismutase and catalase.

• Maintaining a balance between free radicals and antioxidants is crucial for overall health and well-being.

• Leading a healthy lifestyle that includes a balanced diet rich in antioxidants, regular exercise, minimizing exposure to environmental toxins, and managing stress can help support the body's antioxidant defense system and minimize the potential damage caused by free radicals.

Reactive oxygen species

• Reactive oxygen species (ROS) are a type of highly reactive molecules derived from oxygen.

• They include free radicals such as superoxide anion (O2•-), hydroxyl radical (•OH), and non-radical species like hydrogen peroxide (H2O2) and singlet oxygen (^1O2).

• ROS are natural byproducts of cellular metabolism and are also generated during various biochemical reactions within the body.

• ROS are produced in the mitochondria, peroxisomes, and certain enzymes such as NADPH oxidases as a result of the incomplete reduction of oxygen during normal cellular metabolism.

• They can also be generated by external factors like environmental pollutants, radiation, toxins, and certain drugs.

• In small amounts, ROS serve important roles in cell signaling, immune response, and regulation of physiological processes.

• However, when ROS levels become excessive or the antioxidant defense system is compromised, a condition called oxidative stress occurs.

• Oxidative stress arises when there is an imbalance between the production of ROS and the body's antioxidant capacity.

• This can lead to cellular damage, as ROS react with various cellular components including proteins, lipids, and DNA.

• Oxidative damage to biomolecules can disrupt cellular function, contribute to the development of diseases, and accelerate the aging process.

• The harmful effects of ROS have been implicated in a wide range of health conditions, including cardiovascular diseases, neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), cancer, diabetes, inflammation, and aging-related conditions.

• ROS can cause DNA mutations, promote inflammation, impair cellular signaling, and damage cell membranes, leading to tissue dysfunction and organ damage.

• To counteract the damaging effects of ROS, the body has a complex antioxidant defense system. Antioxidants scavenge and neutralize ROS, minimizing their harmful effects.

• Antioxidants can be endogenous (produced by the body) or exogenous (obtained from the diet or supplements).

• Endogenous antioxidants include enzymes such as superoxide dismutase, catalase, and glutathione peroxidase.

• Exogenous antioxidants are obtained from a variety of dietary sources, including vitamins (such as vitamins C and E), minerals (such as selenium and zinc), and plant-based compounds like flavonoids and carotenoids.

• Maintaining a healthy balance between ROS production and the antioxidant defense system is crucial for overall health and preventing oxidative stress-related diseases.

• This can be achieved by adopting a healthy lifestyle that includes a balanced diet rich in antioxidants, regular exercise, stress management, avoiding exposure to environmental toxins, and avoiding behaviors such as smoking and excessive alcohol consumption, which can increase ROS production.

Free radicals are produced within cells

• Free radicals are produced within cells through various processes, both as byproducts of normal cellular metabolism and as a result of external factors.

• Here are some key sources of free radical production in cells:

1. Mitochondrial respiration: Mitochondria, the powerhouses of the cell, generate energy through oxidative phosphorylation. During this process, a small fraction of oxygen molecules can undergo incomplete reduction, leading to the production of superoxide anion (O2•-) as a free radical. This occurs primarily at the electron transport chain, where electrons escape and react with oxygen.

2. Inflammation and immune response: Immune cells, such as neutrophils and macrophages, produce free radicals as part of their defense mechanisms against pathogens. They generate reactive oxygen species (ROS) like superoxide anion (O2•-) through an enzyme called NADPH oxidase, which helps destroy invading microorganisms. However, excessive ROS production during chronic inflammation can lead to tissue damage.

3. Xenobiotic metabolism: Cells have enzymatic systems, particularly in the liver, that help detoxify and eliminate foreign substances (xenobiotics) from the body. The metabolism of some xenobiotics, such as drugs, alcohol, and pollutants, can generate free radicals as a byproduct. For example, certain drugs are metabolized by the cytochrome P450 system, which can produce ROS during the process.

4. Radiation exposure: Ionizing radiation, such as X-rays and gamma rays, can directly ionize molecules in cells, leading to the formation of free radicals. These high-energy particles can break chemical bonds, including those in water molecules, resulting in the production of hydroxyl radicals (•OH), which are highly reactive free radicals.

5. Environmental factors: Cells can be exposed to environmental factors that induce free radical production. For instance, exposure to air pollution, cigarette smoke, ultraviolet (UV) radiation from the sun, and certain chemicals can trigger the formation of free radicals in cells.

It's important to note that while the production of free radicals is a natural and essential process in cells, an imbalance between their production and the body's antioxidant defense system can lead to oxidative stress and potential damage to cellular components. The body relies on antioxidant systems, both endogenous (e.g., enzymes like superoxide dismutase and catalase) and exogenous (e.g., dietary antioxidants), to neutralize and mitigate the harmful effects of free radicals.

Damaging reactions of free radicals on lipids, proteins, Carbohydrates, nucleic acids

• Free radicals can cause damage to various biomolecules in cells, including lipids, proteins, carbohydrates, and nucleic acids.

• Here's an overview of the damaging reactions of free radicals on each of these biomolecules:

1. Lipids:

• Lipid Peroxidation: Free radicals, especially reactive oxygen species (ROS), can initiate lipid peroxidation, a chain reaction that damages lipids.

• ROS, such as hydroxyl radicals (•OH) and peroxyl radicals (ROO•), attack polyunsaturated fatty acids in cell membranes, leading to the formation of lipid radicals.

• These lipid radicals then react with molecular oxygen to produce lipid peroxyl radicals, which can propagate the chain reaction by attacking other lipids.

• Lipid peroxidation results in the degradation of cell membrane lipids, compromising their structural integrity and causing membrane damage and dysfunction.

2. Proteins:

• Protein Oxidation: Free radicals can oxidize amino acid residues in proteins, leading to protein oxidation.

• ROS can directly react with proteins, causing modifications in their structure and function.

• This can include oxidation of sulfur-containing amino acids (such as cysteine and methionine), oxidation of aromatic amino acids (such as tyrosine and phenylalanine), and carbonylation of amino acid side chains.

• Protein oxidation can impair enzymatic activity, alter protein-protein interactions, and contribute to protein misfolding and aggregation.

3. Carbohydrates:

• Glycation and Advanced Glycation End Products (AGEs): Free radicals can contribute to the formation of advanced glycation end products (AGEs).

• Glycation occurs when free radicals react with sugars (e.g., glucose) to form reactive carbonyl species, which then react with proteins or lipids.

• This process leads to the formation of AGEs, which are cross-linked protein or lipid structures that are resistant to degradation.

• AGEs can accumulate in tissues and contribute to the development of various age-related diseases, such as diabetes, atherosclerosis, and neurodegenerative disorders.

4. Nucleic Acids:

• DNA Damage: Free radicals, particularly hydroxyl radicals (•OH), can directly attack DNA, causing various types of damage.

• This includes oxidative modifications to DNA bases, such as oxidation of guanine to 8-hydroxyguanine (8-OHdG), and strand breaks in the DNA backbone.

• DNA damage by free radicals can lead to mutations, genomic instability, and impair DNA replication and transcription processes.

It's important to note that these damaging reactions can have significant consequences for cellular function and contribute to the development of various diseases, including cancer, cardiovascular diseases, neurodegenerative disorders, and aging-related conditions. The body's antioxidant defense system, including endogenous antioxidants and dietary antioxidants obtained from the diet, helps counteract the damaging effects of free radicals and minimize their impact on biomolecules.