Oxidative Stress and Reactive Oxygen Species

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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?

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?

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?

Lead

Arsenic

Chromium

Vanadium (correct)

The carcinogenic effects of heavy metals are mainly related to their impact on which transcription factors?

AP-1 and p53 (B) Signup and view all the answers

What substance is formed when lipid peroxides react with redox metals?

4-hydroxynonenal (B) Signup and view all the answers

What is the primary way hydrogen peroxide (H2O2) can damage DNA?

Produces hydroxyl radicals in the presence of transition metal ions (B) Signup and view all the answers

Which of the following is a characteristic of singlet oxygen (1O2)?

Is highly reactive toward most olefins (A) Signup and view all the answers

Which reaction involves hydroxyl radicals being produced from hydrogen peroxide?

Fenton Reaction (C) Signup and view all the answers

What distinguishes hydrogen peroxide from superoxide regarding cellular effects?

H2O2 can cross cell membranes, while superoxide cannot (B) Signup and view all the answers

Which mechanism does not result in the formation of hydroxyl radicals?

Ozone decomposition at low temperatures (C) Signup and view all the answers

How can hydrogen peroxide (H2O2) be removed from cells?

By addition of catalase outside the cells (B) Signup and view all the answers

What is a significant property of hydroxyl radicals (OH•)?

They can abstract hydrogen atoms (B) Signup and view all the answers

What is the result of the reaction of nitric oxide with superoxide?

Production of hydroxyl radicals and NO2 radicals (B) Signup and view all the answers

What defines a free radical?

An atom or molecule with one or more unpaired electrons. (A) Signup and view all the answers

How can free radicals be generated?

Through homolytic fission of covalent bonds. (B) Signup and view all the answers

What happens when two free radicals react with each other?

They form stable nonradicals. (D) Signup and view all the answers

Which of the following correctly describes an oxidant?

A substance that accepts electrons from another compound. (D) Signup and view all the answers

What is a characteristic of free radicals?

They are highly reactive. (B) Signup and view all the answers

Which of the following is NOT a function of free radicals in the body?

Generating energy through oxidation. (C) Signup and view all the answers

What effect do free radicals have when reacting with stable molecules?

They generate more free radicals. (A) Signup and view all the answers

What denotes a free radical in chemical nomenclature?

A superscript dot next to the symbol. (B) Signup and view all the answers

What initiates lipid peroxidation in biological systems?

Reactive oxygen species (ROS) (B) Signup and view all the answers

During the propagation phase of lipid peroxidation, what is produced when a fatty acid radical reacts with molecular oxygen?

Lipid hydroperoxide (B) Signup and view all the answers

What role do hydroperoxides play in lipid peroxidation?

They stimulate further lipid peroxidation. (D) Signup and view all the answers

What is the main composition of a lipid bilayer membrane?

Phospholipids and glycolipids (C) Signup and view all the answers

Which phase in lipid peroxidation is characterized by the formation of a non-radical species?

Termination phase (B) Signup and view all the answers

What is the primary reason polyunsaturated fatty acids are more susceptible to lipid peroxidation?

They have multiple double bonds. (D) Signup and view all the answers

What is produced during the initiation phase of lipid peroxidation?

Fatty acid radical (D) Signup and view all the answers

Which type of molecule is involved in speeding up the termination of lipid peroxidation?

Neutralizing agents (D) Signup and view all the answers

What role do reactive oxygen species (ROS) play in cancer cells?

They induce and maintain the oncogenic phenotype. (C) Signup and view all the answers

Which statement about antioxidants is true?

Antioxidants are capable of inhibiting the oxidation of other molecules. (D) Signup and view all the answers

What is the primary function of superoxide dismutase (SOD)?

To catalyze the breakdown of superoxide anion. (D) Signup and view all the answers

Which of the following is an example of a non-enzymatic antioxidant?

Vitamin C (D) Signup and view all the answers

Where is catalase primarily localized in mammalian cells?

In the matrix of peroxisomes. (D) Signup and view all the answers

Which type of antioxidant is superoxide dismutase categorized under?

Enzymatic antioxidant. (D) Signup and view all the answers

How do antioxidants function in the body?

They terminate chain reactions initiated by free radicals. (B) Signup and view all the answers

What is the molecular weight classification of catalase?

Around 220,000 and above. (D) Signup and view all the answers

What are the irreversible oxidation products of amino acids most frequently formed?

Hydroxylated and carbonylated amino acid derivatives (B) Signup and view all the answers

What mechanism contributes to protein carbonylation?

Direct attack by reactive oxygen species on amino acid side chains (B) Signup and view all the answers

What effect does oxidative degradation enhanced by metal cofactors have on proteins?

Inactivates the enzyme by altering the cation binding site (B) Signup and view all the answers

Which of the following types of DNA damage is not caused by oxidative agents?

Synthesis of extra DNA strands (B) Signup and view all the answers

What specific product is formed from the degradation of bases in DNA due to oxidative damage?

8-hydroxyguanine (C) Signup and view all the answers

How do specific proteases in E.coli respond to oxidized proteins?

By degrading oxidized proteins (B) Signup and view all the answers

Which amino acids are primarily susceptible to oxidative modification?

Proline, arginine, serine (D) Signup and view all the answers

What is one of the most effective proteolytic mechanisms for degrading oxidized proteins?

Hydrolysis by specific compartment proteases (C) Signup and view all the answers

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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Description

Test your knowledge on the role of reactive oxygen species (ROS) in cellular signaling and oxidative stress. This quiz covers various aspects, including the effects of growth factors, lipid peroxidation, and the role of metals in oxidative damage. Challenge yourself and deepen your understanding of these crucial biochemical processes.