Cell Structure And Mechanisms of Cell Injury Flashcards
Phospholipids of the plasma membrane?
Phosphatidylserine
Phosphatidylcholine
Phosphatidylinositol
Sphingomyelin
What are lipid rafts?
Horizontal associations of sphingomyelin and cholesterol
What phospholipid will flips to the outside of the cell signals itself for phagocytosis ?
Phosphatidylserine
Plasma membrane components important in cell-cell interactions and cell-matrix interactions
Glycoplipids ad sphingomyelin
What are the 4 general arrangements of proteins and glycoproteins?
Integral/transmembrane
Linked to the membrane via lipid or cholesterol
GPI-linked protein (glycosylphosphatidylinositol)
Non-covalent associated
__________ creates a hydrophilic pore and permits rapid movement of solutes
Channels
__________ binds a solute and undergoes conformational changes to transport solute across the membrane
Carriers
What are the two forms of endocytosis ?
Potocytosis - caveolate-mediated
Pinocytosis -receptor-mediated (clathrin coated vesicle)
What are the functions of the cytoskeleton
Maintain shape
Maintain polarity
Organize the relationship of intracellular organelles
Mobilize
What are the three classes of the cytoskeleton
Actin microfilaments
Intermediate filaments
Microtubules
Thinnest filament comprised of globular protein (G- protein) subunits
Actin
Muscle contraction and in cell shape/movement
Tissue specific cytoskeleton component that functions in tensile strength, cell shape, signal transduction,regulation of nuclear transcription, ect.
Intermediate filaments
Intermediate filament of epithelial cells
Cytokeratin
Intermediate filament of mesenchymal cells
Vimentin
Intermediate filament of muscle cells
Desmin
Thickest cytoskeleton component of a- and B- tubules that function as cables for molecular motor proteins
Microtubules
Continuous barrier that is highly resistant to paracellular ion movement and helps maintain cell polarity
Tight junctions (occluding junctions)
Attach cells to other cells or the ECM
Desmosomes (anchoring junctions).
Mediates passage of chemical or electrical signals from one celll to another
Gap junctions (communicating junctions)
Site of synthesis of all transmembrane proteins and lipids
ER
Where are ribosomes found
Bound to surface of RER
Cytosol
What modifications can be made to proteins in the ER and what mediates this process
Oligomerize
Disulfide bonds
Sugar moieties attached
Chaperone molecules retain proteins in ER until all modification ad folding is complete
Where is intracellular calcium sequestered?
Smooth ER
Mitochondria
What occurs to proteins in the Golgi apparatus
Glycosylation
Function of lysosomes
Digest macromolecules
Acid hydrolases (tagged with mannose-6-phosphate) are delivered to lysosome
Protesosomes identify proteins by ____________ maker
Ubiquitin
What are the functions of the mitochondria ?
Aerobic metabolism
->TCA cycle and election transport chain
Regulate apoptosis
What is the Warburg effect?
In rapidly growing cells, TCA cycle is used for building blocks on lipid, nucleic acid, and protein -> glucose and glutamate provide carbon=>decreased production of ATP/glucose molecules
DNA is wrapped around ____________ to make chromatin
Histones
What are the 6 mechanisms of cell injury?
Depletion of ATP Mitochondrial damage CA2+ influx and loss of CA homeostasis Oxidative stress Defect in membrane permeability DNA/protein damage
What can cause hypoxia/anoxia?
Inadequate oxygenation of blood
Reduced transport of O2 in blood
Reduction of blood supply
Blockage of respiratory enzymes
A partial reduction in O2 delivery to a tissue
Hypoxia
No O2 delivery to a tissue
Anoxia
What infectious agent can cause cell injury??
Virus Bacteria Fungus Protozoa Metazoan parasites
How can immune dysfunction cause cell injury
Congenital defect-eg SCID
Acquired defect - viral/chemical/drugs
Autoimmune disease
Hypersensitivity reactions
What is the fundamental cause of necrotic cell death??
Deletion of ATP
ATP is produced by what 2 primary metabolic pathways? What common substrate do they have?
- Aerobic (TCA)
- Anaerobic (Glycolysis)
Glucose
ATP depletion can be associated with what two types of injury?
Hyopxic
Toxic
What are consequences to the cell when ATP is depleted?
Na/K ATPase failure -> cell swelling/ ER swelling/ PM damage
Altered cell metabolism -> anaerobic glycolysis -> lactic acid -> increased pH -> loss of enzyme function
Ribosome detachment-> decreased protein synthesis
What are the three major consequences of mitochondrial damage?
Mitochondrial permeability transition pore
Reactive oxygen species
Apoptotic pathways
What is the mitochondrial permeability transition pore and when opened, what occurs??
High-conductance channel in the mitochondrial membrane
=> loss of membrane potential -> failure of oxidative phosphorylation -> more ATP loss
What are the sources of calcium?
Extrinsic
Intrinsic -> SER or mitochondria
What can cause accumulation of Ca2+
Extracellular Ca increase -> into cell (infectious agent)
Intracellular Ca release -> opening of mitochondrial permeability transition pore (MPTP) and release fro ER
Accumulation of Ca2+ leads to activation of what enzymes?
Phospholipases - membrane damage
Proteases
Endonucleases - DNA fragmentation
ATPases -breakdown ATP
Accumulation of Ca2+ leads to what 3 major forms of damage
Membrane damage
Nuclear damage
ATP depletion
Reactive oxygen species are normally produced by?
Mitochondrial respiration
How do ROS initiate autocatalytic reactions?
Have and unstable electron configuration
Interacts with adjacent molecules: proteins, lipids, carbohydrates, nucleic acids
Oxidative stress leads to what pathological processes?
Cell injury
Cancer
Aging
Degenerative disease
What is the major producer of ROS in inflammatory reaction?
Activated leukocytes (neutrophil and macrophages)
-> destroy microbes and clean up dead cells
What causes the formation of reactive oxygen species?
Inflammation -activated WBC
Transition metals -donate or accept free electrons
Nitric oxide -chemical mediator/ generated endothelial cells /macrophages / neurons (free radical)
How are free radicals removed?
Spontaneous decay
Antioxidants- block initiation or inactivate
Storage and transport proteins - transferrin, ferritin, ceruloplasmin
Enzymes- catalase, superoxide dismutase, glutathione peroxidase
What are the pathologic effects of free radicals ?
Lipid peroxidation in membranes -> extensive membrane damage
Oxidative modification of proteins -> damage active sites, change confirmation, and enhance degradation
Lesions in DNA-> Cell aging, malignant transformation
How does lipid peroxidation damage the membrane?
- forms peroxidases->autocatalytic rxn (propagation)
- ->decreased phospholipid synthesis
- ->increased phospholipid breakdown
- -> cytoskeletal abnormalities
- activation of proteases-> damaged cytoskeleton
- cells stretch and rupture
What is the mode of action of oxidative modification of proteins ?
Oxidation of aa side chains, and formation of protein cross-linkages , or oxidation of protein backbone
- mitochondrial membrane damage
- plasma membrane damage
- injury to lysosomal membrane
What is the mode of action of DNA lesions for ROS
Single stranded or double stranded breaks, cross-linking of DNA strands, formation of adducts
How can the plasma membrane be damaged?
Reactive oxygen species
Decreased phospholipid synthesis
Increased phospholipid breakdown
Cytoskeletal abnormalities
What are the consequences of membrane damage?
Mitochondrial membrane damage-> open the MPTP -> decreased ATP
Plasma membrane damage -> loss of osmotic balance and loss of cell contents
Injury to lysosome -> leakage to enzymes -> digestion of RNA/DNA/protein
What are the types of protein damage?
Accumulation of misfolded proteins
Cells have repair mechanisms for misfolded proteins
When overwhelmed-> proteins accumulated in the ER
How is DNA damaged?
Radiation, cytotoxic anti cancer drugs, hypoxia
Cells have repair mechanisms
When overwhelmed-> initiates apoptosis
