Podcast
Questions and Answers
What characteristic defines free radicals at the molecular level?
What characteristic defines free radicals at the molecular level?
- A net positive charge
- Paired electrons in the outer shell
- Stable, non-reactive structure
- Unpaired electron in the outer shell (correct)
Which of the following enzymes is NOT directly involved in the formation of free radicals?
Which of the following enzymes is NOT directly involved in the formation of free radicals?
- Nitric oxide synthase
- Superoxide dismutase (correct)
- Myeloperoxidase
- NADPH oxidase
What role do free radicals play in cellular signaling?
What role do free radicals play in cellular signaling?
- They solely cause damage and have no beneficial roles
- They immediately halt all signaling processes
- They are essential for signal transduction in certain pathways (correct)
- They only interfere with cell membrane integrity, disrupting signaling indirectly
Which condition is associated with the deleterious effects of RONS?
Which condition is associated with the deleterious effects of RONS?
What is the typical progression of cellular response as ROS levels increase, according to the 'Cellular impact of ROS' diagram?
What is the typical progression of cellular response as ROS levels increase, according to the 'Cellular impact of ROS' diagram?
How does superoxide interact with other molecules in the body?
How does superoxide interact with other molecules in the body?
From which source is superoxide primarily generated within the cell?
From which source is superoxide primarily generated within the cell?
Which statement accurately describes the process of NOX2 activation?
Which statement accurately describes the process of NOX2 activation?
What role does NADPH oxidase assembly and activation play in pathogen clearance?
What role does NADPH oxidase assembly and activation play in pathogen clearance?
What role do human neutrophils play in the free radical host defense system?
What role do human neutrophils play in the free radical host defense system?
What is the key characteristic of the inducible isoform of nitric oxide synthase (iNOS)?
What is the key characteristic of the inducible isoform of nitric oxide synthase (iNOS)?
What triggers iNOS expression?
What triggers iNOS expression?
What role do neutrophils and macrophages play in myocardial infarction?
What role do neutrophils and macrophages play in myocardial infarction?
How is peroxynitrite formed in biological systems?
How is peroxynitrite formed in biological systems?
What effect does peroxynitrite have on cellular proteins?
What effect does peroxynitrite have on cellular proteins?
What is the role of Arginine in Nitric Oxide production?
What is the role of Arginine in Nitric Oxide production?
How do free radicals lead to lipid peroxidation in cellular membranes?
How do free radicals lead to lipid peroxidation in cellular membranes?
What outcome is most associated with oxidative stress?
What outcome is most associated with oxidative stress?
Which is an accurate description of oxidative stress?
Which is an accurate description of oxidative stress?
How is hydrogen peroxide (H2O2) formed in cells?
How is hydrogen peroxide (H2O2) formed in cells?
What is a crucial factor in determining the overall impact of oxidative stress on human health?
What is a crucial factor in determining the overall impact of oxidative stress on human health?
What distinguishes 'reactive oxidants' from 'free radicals'?
What distinguishes 'reactive oxidants' from 'free radicals'?
Why is the rapid inactivation of nitric oxide (NO•) important in biological systems?
Why is the rapid inactivation of nitric oxide (NO•) important in biological systems?
What occurs after neutrophils are activated during inflammation?
What occurs after neutrophils are activated during inflammation?
What is the significance of the Haber-Weiss reaction in the context of oxidative stress?
What is the significance of the Haber-Weiss reaction in the context of oxidative stress?
Which statement accurately describes how superoxide radicals are generated in the mitochondrial electron transport system?
Which statement accurately describes how superoxide radicals are generated in the mitochondrial electron transport system?
Which factor greatly affects nitric oxide's (NO•) function?
Which factor greatly affects nitric oxide's (NO•) function?
Which process is directly linked to the 'dual roles' of free radicals in biological systems?
Which process is directly linked to the 'dual roles' of free radicals in biological systems?
What characteristic makes superoxide a highly reactive molecule?
What characteristic makes superoxide a highly reactive molecule?
The cellular damage of oxidative stress is linked to the deficiency of which system?
The cellular damage of oxidative stress is linked to the deficiency of which system?
What is the most important effect that nitric oxide synthases (NOS) have?
What is the most important effect that nitric oxide synthases (NOS) have?
What determines the regulatory effects of RONS, such as in cell signaling?
What determines the regulatory effects of RONS, such as in cell signaling?
What role does NADPH oxidase play in the context of free radical production during the host defense?
What role does NADPH oxidase play in the context of free radical production during the host defense?
Where does the production of hydroxyl radicals primarily occur in cells?
Where does the production of hydroxyl radicals primarily occur in cells?
What explains why superoxide cannot diffuse far in biological systems?
What explains why superoxide cannot diffuse far in biological systems?
What is the significance of glutathione in the context of peroxynitrite exposure?
What is the significance of glutathione in the context of peroxynitrite exposure?
How does the overproduction of ROS typically affect cellular lipids, proteins, and DNA?
How does the overproduction of ROS typically affect cellular lipids, proteins, and DNA?
Superoxide is known to have limited diffused ability. Which property gives it this characteristic?
Superoxide is known to have limited diffused ability. Which property gives it this characteristic?
Flashcards
Free Radicals
Free Radicals
Molecules with one or more unpaired electrons, making them highly reactive and unstable.
Oxygen consumption and free radicals
Oxygen consumption and free radicals
Aerobic life consumes oxygen, with about 5% resulting in free radicals.
Superoxide characteristics
Superoxide characteristics
Superoxide is a primary radical ROS, highly reactive, poorly lipid-soluble, and interacts to form other ROS/RNS.
Causes of superoxide creation
Causes of superoxide creation
Signup and view all the flashcards
Hydroxyl Radical (•OH)
Hydroxyl Radical (•OH)
Signup and view all the flashcards
Hydrogen Peroxide (H₂O₂) formation
Hydrogen Peroxide (H₂O₂) formation
Signup and view all the flashcards
Nitric Oxide (NO•)
Nitric Oxide (NO•)
Signup and view all the flashcards
Peroxynitrite (ONOO-)
Peroxynitrite (ONOO-)
Signup and view all the flashcards
Lipid Peroxidation by free radicals
Lipid Peroxidation by free radicals
Signup and view all the flashcards
Oxidative Stress
Oxidative Stress
Signup and view all the flashcards
Defining characteristics of a Free Radical
Defining characteristics of a Free Radical
Signup and view all the flashcards
Reactive Oxidants
Reactive Oxidants
Signup and view all the flashcards
Neutrophils and Inflammation
Neutrophils and Inflammation
Signup and view all the flashcards
Study Notes
Free Radicals, Antioxidants, and Oxidative Stress
- Free radicals, antioxidants, and oxidative stress are important concepts
Outline
- The presentation will cover definitions and sources of free radicals
- The presentation will cover types of free radicals
- The presentation will cover antioxidants (exogenous and endogenous)
- The presentation will cover oxidative stress and damage in disease
Oxygen Free Radicals
- Aerobic life
- Approximately 5% O2 consumption produces free radicals
Definition & Characteristics of Free Radicals
- Free radicals are highly reactive and unstable
- Free radicals include a Singlet electron
- Free radicals have an independent existence
- ROS & RNS
- Free radicals formation occurs in the following ways:
- Enzyme catalyzed formation occurs with NADPH oxidase, myeloperoxidase, and nitric oxide synthase
- Metal ion-catalyzed formation occurs with Fe2+, Cu+
- Accidental electron transfer to O₂
- Ionizing radiations result in free radical formulation
- Free radicals have dual roles including physiology to pathology
Dual Effects of RONS
- Beneficial effects of RONS:
- Indispensable to cellular processes
- Role in cellular signaling
- Normal cell functions
- Defense against microorganisms
- Deleterious effects of RONS:
- Oxidative stress & diseases
- CVD
- Neurological disorders
- Cancer
- Diabetes
- Ageing
Cellular impact of ROS
- ROS levels correlate to cellular impact
- Proliferation with low ROS levels, Apoptosis with mid ROS levels, and Necrosis with high ROS levels
Oxygen Free Radicals
- Two classes of oxygen free radicals includes:
- Reactive oxygen species (ROS)
- Reactive nitrogen species (RNS)
- Specific oxygen free radicals include:
- Superoxide (02)
- Nitric oxide (NO˚)
- Hydroxyl (OH)
- Nitrogen dioxide (NO2)
- Peroxyl (RO0°)
- Lipid peroxyl (LOO˚)
Reactive Oxidants
- Reactive oxidants can lead to free radical formation
- Include:
- Hydrogen peroxide (H2O2)
- Hypochlorous acid (HOCI)
- Nitrous acid (HNO2)
- Peroxynitrite (ΟΝΟΟ¯)
- Dinitrogen trioxide (N2O3)
Superoxide (02)
- Superoxide is a primary radical ROS
- Superoxide is highly reactive
- The formula for Superoxide is: O₂ + e- → 02-
- Superoxide has limited lipid solubility
- Superoxide unable diffuse far
- Superoxide interacts with other molecules to generate other ROS & RNS
02- formation & roles
- Major sources:
- Mitochondrial electron transport system
- Electron transfer from semiquinone radical (CoQH) to O₂ is accidental
- NADPH oxidases (membrane bound)
- Electron transfer from NADPH to O2
- Generate superoxide
- Cell signaling & immunity
- Mitochondrial electron transport system
NADPH oxidase families
- Isoforms: NOX1-5, Duox1 & 2
- Tissue distribution: NOX1 (endothelial), NOX2 (phagocytes)
- Subunit composition
- Regulation
NOX2
- NOX2 is found in Phagocytes (neutrophils & phagocytes), and was discovered first
- NOX2 Active form: includes six subunits
- NOX2 Unstimulated form includes:
- Core complex (Flavocytochrome b558 (cyt b558))
- Transmembrane hetrodimer of gp91phox & p22 complex
- Flavin & heme prosthetic groups
- Regulatory complex (p40, p47, p67): cytosolic
- Rac (GDP bound): cytosolic
- Core complex (Flavocytochrome b558 (cyt b558))
NOX2 activation
- Phosphorylation of p47
- Recruitment of regulatory complex along with GTP bound Rac (GTPase) to cyt b558
- Phosphorylated p47 binds C-terminus of p22
- Active NADPH oxidase:
- Flavin & heme prosthetic groups
- Superoxide formation
ROS & Pathogen Clearance
- Phagosome
- NADPH oxidase assembly & activation
- ROS generation
- Pathogen clearance
- ROS induced ER stress
- MAPK signaling
- Proinflammatory cytokines
- Pathogen killing
Free Radical Host Defense System
- Human neutrophils have dual roles
- Generate free radicals through enzyme catalysis
- Inflammatory diseases
- Innate immunity against pathogens
- Phagosome
- NADPH + O2 → O2 + NAPD+ ( NAPH oxidase)
- 202 ¯ + 2H+ → H₂O₂ (spontaneous)
- H2O2 + Cl- →HOCI (Hypochlorous acid)→ OCl + HO
- (Myeloperoxidase (heme protein (Fe2+/Fe3+))
- O₂ & HO: bactericidal
- Deficiency of NADPH oxidase: chronic granulomatous
Infection & Apoptosis
- Infection
- ROS Production
- ER stress-mediated apoptosis
- Pathogen Clearance
Superoxide Formation
- Mitochondrial System
- Accidental encounter of CoQ with O2
Hydroxyl Radical (OH) Formation
- The Hydroxyl Radical is the most potent reactive ROS (initiates chain reactions)
- Haber-Weiss reaction (H₂O2 + O2¯) reaction
- H2O2 is lipid soluble and can diffuse through membranes
- Fenton reaction (H₂O2 + Fe2+)→ ·OH +OH¯)
- Localized OH generation at Fe2+ or Cut containing sites (mitochondria)
- Ionizing radiations: aqueous environment
H2O2 Formation
- H2O2 Formation through Catabolism of purines
- H2O2 Formation through Peroxisomal oxidation of fatty acids
Other Free Radicals
- Peroxyl (ROO˚) and lipid peroxyl (LOO˚) radicals:
- Products of lipid peroxidation
- Attack by O2 or 'OH radicals
- Nitric oxide (NO): produced endogenously by nitric oxide synthase
- RNS are derived principally from nitric oxide (NO) radical
- NO· combines with O₂ or superoxide to produce additional RNOS
Nitric Oxide Radical
- Nitric oxide synthases includes (nNOS, ENOS, INOS)
- Constitutive isoforms include (nNOS, ENOS)
- Ca2+-calmodulin-dependent
- Activated by high levels of Ca2+
- Inducible isoform (iNOS)
- Arginine, O2, NADPH
- Coenzymes includes FMN, FAD, heme, and tetrahydrobiopterin
- NO· Diffuses through water and lipid membranes
- NO is rapidly inactivated by nonspecific binding to many molecules
- Cells that produce NO need to be close to the target cells
iNOS
- iNOS is a Cell of the immune system
- iNOS is found in Macrophages
- iNOS is found in Astroglia Regulated principally by induction of gene transcription
- iNOS expression induced by:
- Bacterial lipopolysaccharide (LPS)
- Inflammatory cytokines
NO and Inflammation
- Neutrophils activated during inflammation
- Expression of iNOS (NO release)
- Activation of NADPH oxidase (02)
- Peroxynitrite (NO + O2), additional RNOS
- Tissue injury
- NO can be released into surrounding
- Neutrophils & macrophages infiltrate to myocardial infarction area
- RNOS formation & extended tissue damage
- Neutrophils play role in chronic inflammation in rheumatoid arthritis
Peroxynitrite (ΟΝΟΟ¯)
- Peroxynitrite is Formed from NO & O₂
- Peroxynitrite is a strong oxidizing agent
- Peroxynitrite is stable and toxic
- Peroxynitrite Can diffuse through membranes & interact with range of targets
- Nitrosylation of active site tyrosine residues in enzymes
- Nitrosylation of glutathione (and other cellular thiols) and thereby alter the cellular redox balance
- Oxidation of lipids, DNA strand breaks, and nitration and deamination of DNA bases
Free Radical-Mediated Cellular Injury
- Lipid peroxidation: O2' or 'OH radicals initiate lipid peroxidation in membranes (mitochondrial, nuclear & endoplasmic reticulum)
- Increase in cellular permeability
- Ca2+ influx and mitochondrial damage
- Protein oxidation and degradation: oxidation of cysteine -SH residues
- Oxidation of DNA (Nuclear and mitochondrial):
- Strand breaks
- Mutations
- RNOS (NO, NO2, and peroxynitrite) have similar effects
Oxidative Stress
- Overproduction of ROS
- Deleterious effects of ROS
- ROS are predominantly implicated in causing cell damage
- Deficiency of antioxidant system (enzymatic and non-enzymatic)
- Damage of cellular lipids, proteins, and DNA
- Human diseases and ageing.
- Balance between beneficial and harmful effects is a very important
Oxidative Stress
- Oxidative stress occurs when ROS/RNS outweigh the cell defenses like antioxidants, or when antioxidants/enzymes cannot compensate for ROS/RNOS
Oxidative Stress Consequences Within a Cell
- Protein Damage
- Respiratory enzyme damage
- Membrane damage
- DNA damage
- Increased permeability
- Massive influx of Ca2+
- Cell Swelling
Organ-Specific Effect of Oxidative Stress
- Oxidative stress affects organ systems and can cause disease.
End
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
