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Questions and Answers
Which of the following receptors is NOT involved in the production of reactive oxygen species (ROS) as a result of activated growth factor receptor signaling?
Which of the following receptors is NOT involved in the production of reactive oxygen species (ROS) as a result of activated growth factor receptor signaling?
- Tumor necrosis factor (TNF-α) receptor
- Platelet derived growth factor (PDGF) receptor
- Transferrin receptor (correct)
- Epidermal growth factor (EGF) receptor
What is the product of lipid peroxidation that results from the attack of radicals on polyunsaturated fatty acids?
What is the product of lipid peroxidation that results from the attack of radicals on polyunsaturated fatty acids?
- Hydroxyl radical
- Nitric oxide
- Superoxide radical
- Malondialdehyde (correct)
Which of the following metals is associated with oxidative stress and has been experimentally linked to the etiology of diabetes?
Which of the following metals is associated with oxidative stress and has been experimentally linked to the etiology of diabetes?
- Lead
- Arsenic
- Chromium
- Vanadium (correct)
The carcinogenic effects of heavy metals are mainly related to their impact on which transcription factors?
The carcinogenic effects of heavy metals are mainly related to their impact on which transcription factors?
What substance is formed when lipid peroxides react with redox metals?
What substance is formed when lipid peroxides react with redox metals?
What is the primary way hydrogen peroxide (H2O2) can damage DNA?
What is the primary way hydrogen peroxide (H2O2) can damage DNA?
Which of the following is a characteristic of singlet oxygen (1O2)?
Which of the following is a characteristic of singlet oxygen (1O2)?
Which reaction involves hydroxyl radicals being produced from hydrogen peroxide?
Which reaction involves hydroxyl radicals being produced from hydrogen peroxide?
What distinguishes hydrogen peroxide from superoxide regarding cellular effects?
What distinguishes hydrogen peroxide from superoxide regarding cellular effects?
Which mechanism does not result in the formation of hydroxyl radicals?
Which mechanism does not result in the formation of hydroxyl radicals?
How can hydrogen peroxide (H2O2) be removed from cells?
How can hydrogen peroxide (H2O2) be removed from cells?
What is a significant property of hydroxyl radicals (OH•)?
What is a significant property of hydroxyl radicals (OH•)?
What is the result of the reaction of nitric oxide with superoxide?
What is the result of the reaction of nitric oxide with superoxide?
What defines a free radical?
What defines a free radical?
How can free radicals be generated?
How can free radicals be generated?
What happens when two free radicals react with each other?
What happens when two free radicals react with each other?
Which of the following correctly describes an oxidant?
Which of the following correctly describes an oxidant?
What is a characteristic of free radicals?
What is a characteristic of free radicals?
Which of the following is NOT a function of free radicals in the body?
Which of the following is NOT a function of free radicals in the body?
What effect do free radicals have when reacting with stable molecules?
What effect do free radicals have when reacting with stable molecules?
What denotes a free radical in chemical nomenclature?
What denotes a free radical in chemical nomenclature?
What initiates lipid peroxidation in biological systems?
What initiates lipid peroxidation in biological systems?
During the propagation phase of lipid peroxidation, what is produced when a fatty acid radical reacts with molecular oxygen?
During the propagation phase of lipid peroxidation, what is produced when a fatty acid radical reacts with molecular oxygen?
What role do hydroperoxides play in lipid peroxidation?
What role do hydroperoxides play in lipid peroxidation?
What is the main composition of a lipid bilayer membrane?
What is the main composition of a lipid bilayer membrane?
Which phase in lipid peroxidation is characterized by the formation of a non-radical species?
Which phase in lipid peroxidation is characterized by the formation of a non-radical species?
What is the primary reason polyunsaturated fatty acids are more susceptible to lipid peroxidation?
What is the primary reason polyunsaturated fatty acids are more susceptible to lipid peroxidation?
What is produced during the initiation phase of lipid peroxidation?
What is produced during the initiation phase of lipid peroxidation?
Which type of molecule is involved in speeding up the termination of lipid peroxidation?
Which type of molecule is involved in speeding up the termination of lipid peroxidation?
What role do reactive oxygen species (ROS) play in cancer cells?
What role do reactive oxygen species (ROS) play in cancer cells?
Which statement about antioxidants is true?
Which statement about antioxidants is true?
What is the primary function of superoxide dismutase (SOD)?
What is the primary function of superoxide dismutase (SOD)?
Which of the following is an example of a non-enzymatic antioxidant?
Which of the following is an example of a non-enzymatic antioxidant?
Where is catalase primarily localized in mammalian cells?
Where is catalase primarily localized in mammalian cells?
Which type of antioxidant is superoxide dismutase categorized under?
Which type of antioxidant is superoxide dismutase categorized under?
How do antioxidants function in the body?
How do antioxidants function in the body?
What is the molecular weight classification of catalase?
What is the molecular weight classification of catalase?
What are the irreversible oxidation products of amino acids most frequently formed?
What are the irreversible oxidation products of amino acids most frequently formed?
What mechanism contributes to protein carbonylation?
What mechanism contributes to protein carbonylation?
What effect does oxidative degradation enhanced by metal cofactors have on proteins?
What effect does oxidative degradation enhanced by metal cofactors have on proteins?
Which of the following types of DNA damage is not caused by oxidative agents?
Which of the following types of DNA damage is not caused by oxidative agents?
What specific product is formed from the degradation of bases in DNA due to oxidative damage?
What specific product is formed from the degradation of bases in DNA due to oxidative damage?
How do specific proteases in E.coli respond to oxidized proteins?
How do specific proteases in E.coli respond to oxidized proteins?
Which amino acids are primarily susceptible to oxidative modification?
Which amino acids are primarily susceptible to oxidative modification?
What is one of the most effective proteolytic mechanisms for degrading oxidized proteins?
What is one of the most effective proteolytic mechanisms for degrading oxidized proteins?
Flashcards
What is a free radical?
What is a free radical?
An atom or molecule with an unpaired electron in its outer orbital.
What is oxidation?
What is oxidation?
A molecule or atom gains oxygen.
What is reduction?
What is reduction?
A molecule or atom loses oxygen.
What is an oxidant?
What is an oxidant?
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What is a reductant?
What is a reductant?
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What is homolytic fission?
What is homolytic fission?
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Why are free radicals highly reactive?
Why are free radicals highly reactive?
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How can free radicals cause chain reactions?
How can free radicals cause chain reactions?
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How does H2O2 damage DNA?
How does H2O2 damage DNA?
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Why is H2O2 effective in damaging DNA?
Why is H2O2 effective in damaging DNA?
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What makes the hydroxyl radical so reactive?
What makes the hydroxyl radical so reactive?
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How is the hydroxyl radical formed by ionizing radiation?
How is the hydroxyl radical formed by ionizing radiation?
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What is the Haber-Weiss reaction?
What is the Haber-Weiss reaction?
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What is the Fenton reaction?
What is the Fenton reaction?
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How does nitric oxide contribute to hydroxyl radical formation?
How does nitric oxide contribute to hydroxyl radical formation?
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What is singlet oxygen?
What is singlet oxygen?
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MAPK Signaling Pathways
MAPK Signaling Pathways
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Reactive Oxygen Species (ROS)
Reactive Oxygen Species (ROS)
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p53 Protein
p53 Protein
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Apoptosis
Apoptosis
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Lipid Peroxidation
Lipid Peroxidation
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Initiation Phase
Initiation Phase
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Propagation Phase
Propagation Phase
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Termination Phase
Termination Phase
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Antioxidant
Antioxidant
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Polyunsaturated fatty acids
Polyunsaturated fatty acids
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Lipid Hydroperoxide
Lipid Hydroperoxide
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Irreversible Oxidation of Amino Acids
Irreversible Oxidation of Amino Acids
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Dityrosine Formation
Dityrosine Formation
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Protein Carbonylation
Protein Carbonylation
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Metal-Catalyzed Protein Oxidation
Metal-Catalyzed Protein Oxidation
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Consequences of Oxidized Proteins
Consequences of Oxidized Proteins
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Oxidative Marking for Degradation
Oxidative Marking for Degradation
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Proteases in Protein Breakdown
Proteases in Protein Breakdown
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Oxidative DNA Damage
Oxidative DNA Damage
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What are Reactive Oxygen Species (ROS)?
What are Reactive Oxygen Species (ROS)?
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What is the "two-faced" nature of ROS?
What is the "two-faced" nature of ROS?
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What are antioxidants?
What are antioxidants?
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Why are antioxidants important?
Why are antioxidants important?
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What are enzymatic antioxidants?
What are enzymatic antioxidants?
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What are non-enzymatic antioxidants?
What are non-enzymatic antioxidants?
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What is Superoxide Dismutase (SOD)?
What is Superoxide Dismutase (SOD)?
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What is Catalase?
What is Catalase?
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Study Notes
Free Radicals and Antioxidants
- Free radicals are atoms or molecules with one or more unpaired electrons in their outer orbital. This makes them electron-deficient and highly reactive.
- Free radicals are represented by a superscript dot (•) after the chemical symbol. Examples include hydroxyl radical (HO•), and superoxide anion (O2•−).
- Free radicals react quickly with other compounds, trying to become stable. This often leads to the generation of new free radicals, forming a chain reaction.
- Free radicals can be formed through the loss of a single electron from a non-radical, or by the gain of a single electron by a non-radical.; or via homolytic fission (breaking a covalent bond, splitting electrons evenly between the products. This is often induced by heat or light).
- Free radicals can damage various tissues. Sometimes, the body's immune system creates free radicals to neutralize viruses and bacteria. Some free radicals at low levels are signaling molecules, playing a role in gene activity. Others kill cancer cells.
- Some species (non-radicals) have strong oxidizing potential and can produce oxidation or be converted into free radicals. Examples include hydrogen peroxide (H2O2), hypochlorous acid (HOCl), ozone (O3), singlet oxygen (¹O2), and peroxynitrite (ONOO⁻). Transition metals (e.g., manganese, iron, cobalt, copper) also contribute to free radical formation.
- The activation of oxygen can occur via two mechanisms: absorption of sufficient energy to reverse the spin on one of the unpaired electrons or monovalent reduction
- The major source of superoxide is from the electron transport chain in mitochondria. Electron leakage from carriers and phagocyte action contribute.
- Superoxide can participate in a dismutation reaction, forming hydrogen peroxide.
- Hydrogen peroxide (H2O2) is not a free radical, but it can cause damage, especially at high concentrations.
- Hydroxyl radicals (OH•) are highly reactive and can damage DNA, proteins, and lipids. Three ways to create hydroxyl radicals are ionizing radiation, the Haber-Weiss reaction, and the Fenton reaction
- Nitric oxide (NO) can react with superoxide to produce peroxynitrite (ONOO⁻), an even more reactive species.
- Lipid peroxidation occurs when free radicals react with polyunsaturated fats (PUFAs) in cell membranes, leading to lipid radical formation and chain reactions. Products of lipid peroxidation include malondialdehyde and 4-hydroxynonenal.
- Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses. This can cause damage to cells, including proteins, lipids, and DNA, potentially leading to various diseases.
- Antioxidants neutralize free radicals, preventing oxidative damage. These include both enzymatic (e.g., superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (e.g., vitamin C, vitamin E, glutathione).
- The cells contain several enzymes that can produce superoxide, include xanthine oxidase, lipoxygenase, cyclooxygenase, NADPH dependent oxidase, and the Mitochondrial electron transport chain.
- The presence of metal cofactors can accelerate oxidative degradation of proteins. This usually involves the metal binding to a protein, reacting with hydrogen peroxide, creating a hydroxyl radical and damaging an amino acid in the protein, often leading to inactivation of the protein.
- Various diseases and physiological conditions, such as ischemia, inflammation in cystic fibrosis, and specific forms of metabolic disorders, can increase the generation of these species.
Ischemia
- Ischemia is a condition of insufficient blood supply to an area of tissue.
- As a result of oxygen deprivation, ATP is converted into xanthine and hypoxanthine. The resulting enzyme xanthine dehydrogenase is proteolytically converted to xanthine oxidase, which upon reperfusion and oxygen restoration can generate dangerous ROS.
- The production of oxygen-free radicals can severely damage tissues, a phenomenon referred to as ischemia-reperfusion injury.
Phagocyte-Derived Free Radicals
- Phagocytes (neutrophils, macrophages, monocytes) release ROS to destroy invading pathogens.
- This process called the respiratory burst, involves the production of superoxide (O2⁻), hydrogen peroxide (H2O2), and hypochlorous acid (HOCl) via NADPH oxidase or xanthine oxidase.
- These ROS are used as antibacterial agents and, in response to inflammation or infection, also produce elastase, which is a protein-degrading enzyme that can lead to lung tissue damage.
Oxidative Damage of ROS
- Oxidative stress is a state characterized by an excess of ROS in the body's cells, disturbing the normal redox balance, resulting in damage to various components of the biological systems.
- This damage can impact lipids, proteins, and DNA.
- Lipid peroxidation is a chain reaction mechanism where ROS remove electrons from lipids, resulting in membrane damage and the formation of toxic byproducts.
Other Diseases
- Age-related macular degeneration (AMD): Retinal metabolic processes can produce reactive oxygen species.
- Insulin-dependent diabetes mellitus (IDDM): Patients often have decreased levels of antioxidants.
- Respiratory diseases: Inhaling oxidants contribute to disease in the lungs.
- Schizophrenia: Membrane abnormalities due to abnormalities in neuronal membrane phospholipids are implicated as a factor.
- Alzheimer's disease (AD): The build-up of toxic amyloid-β proteins (Aβ) contributes to membrane damage via lipid peroxidation.
Synthesis of NO
- Nitric oxide synthase (NOS) is required to produce NO.
- Different types of NOS (I, II, and III) produce NO from L-arginine but their amounts and cellular localization differ.
Antioxidants
- Antioxidants are molecules that can inhibit the oxidation of other molecules, thus preventing the production of free radicals and protecting the cells from oxidative damage.
- They include enzymatic antioxidants (e.g., superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (e.g., vitamin C, vitamin E, and glutathione).
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