Cell 2 Flashcards
What constitutes 25 to 75% of the mass of the membrane?
proteins
What can be removed from the plasmalemma with salt solutions?
peripheral proteins
What are the types of integral proteins?
monolayer and transmembrane
What protein is involved in Alzheimer’s disease?
beta-amyloid precursor protein
What kind of protein is beta-amyloid precursor protein (beta-APP)?
transmembrane protein
Why is beta-amyloid precursor protein important?
- Neuronal migration during development
- Synaptic formation and repair
- Cell signaling
- Long-term potentiation of memory
- Cell adhesion
In Cruetzfeldt-Jakob disease, what protein is involved? And what does it do?
prion protein (PrP) of neurons, it is converted to an abnormal variant
What is a prion protein?
A glycosylated, GPI-anchored, cell surface protein
What does the abnormal variant of prion protein do?
- misfolded prion (alpha-helix to beta-sheet)
- forms cross-linked filaments that are resistant to proteolysis
- also accelerates conversion of normal PrP to the same form (infectious in this context)
What are some functions of normal prion proteins?
- neuroprotective against ischemia
- control circadian rhythms
- serve to organize the myelin sheath
How do amyloid peptides aggregate?
abnormal cleavage of beta amyloid precursor protein
Why are amyloid-peptide aggregates bad?
they clump together and form amyloid fibrils that arrange into plaques, they are also resistant to proteolysis
- the accumulation of plaques are the cause for Alzheimer’s.
What stain can be used to identify amyloid plaques?
Congo Red stain
What are the functions of membrane proteins?
- pumps and carriers
- channels
- receptors
- linker proteins
- enzymes
- structural
What do pumps (membrane proteins) do?
use ATP to move cargo across the membrane
What do carriers (membrane proteins) do?
passively move cargo across the membrane (do not require energy)
What do channel proteins do?
they respond to signals and serve as doorways into or out of the cell
What do receptor proteins do?
specific ligands bind to them to produce a signal cascade
What do linker proteins do?
they allow structural proteins of the cell and the ECM to link and interact
What do structural proteins do?
they form connections with adjacent cells and/or the ECM
Pharmacologic agents may act on what type of proteins to produce a therapeutic effect?
receptors as agonists or antagonists
How do antagonists work?
block the signal and reduce the effect of the receptor
How do agonists work?
they mimic the effect of the ligand (signal)
What does up regulation of receptors mean?
number of receptors on the membrane increases
What does down regulation of receptors mean?
number of receptors on the membrane decreases
What is the clinical relevance in estrogen receptors that needs to be taken under consideration when treating a patient with breast cancer?
estrogen receptors are not in the membrane of cells (they are located in the nucleus). Determining if a patient has estrogen receptors will help decide on pursuing a hormonal treatment plan
What is Na+/K+ ATPase?
protein pump (transmembrane protein) that pumps sodium and potassium against their concentration gradients, using ATP.
Which has a lower level of sodium normally? Cytosol or ECM?
cytosol
Which has a high level of potassium normally? Cytosol or ECM?
cytosol
Na+/K+ ATPase pumps what out of the cell and what into the cell?
3 Na+ out and 2 K+ in
What is one of the function of Na+/K+ ATPase?
to regulate intracellular volume
How does the Na+/K+ ATPase regulate intracellular volume?
Sodium flows into the cell naturally (water follows), the Na+/K+ ATPase can counteract this action by pumping sodium out of the cell, causing water to leave as well.
In which direction are Ca++ and Na+ are pumped?
Ca++ out of the cell and Na+ into the cell
What does moving calcium out of cardiac muscle cells do to heart contractions?
decrease the force
A patient is having ventricular failure (heart failure), what should you do as far as calcium concentrations?
Maintain as much calcium ions inside the cardiac cells as possible because pumping calcium ions out decreases the force of contraction.
What is the function of Digoxin and what is it used for?
it partially inhibits the Na+/K+ pump, this allows the intracellular sodium level to rise, leading to the inhibition of the calcium/sodium pump, thus an increase in force of contraction in the heart (good for patients with heart failure)
The role of Na+/K+ pump in the co-transport of glucose and sodium is an example of what type of transport?
secondary active
Does the Na+-driven glucose symport require energy?
No
In order to maintain concentration of sodium ions across the membrane, what must the cell do?
Pump sodium out of the cell via the Na+/K+ pump, thus this energy is spent secondarily
Multidrug resistant (MDR) transporters belong to what subfamily?
primary transporter proteins that are ATPases
Where is MDR-1 expressed? What is its function?
- kidney, intestine, liver and blood-brain barrier
- transports drugs
What does MDR-2 transport?
conjugated (direct) bilirubin
Where is MDR-3 expressed? What is its function?
- liver
- functions as a flippase of phosphatidylcholine, flips it to the outer cellular membrane of hepatocytes so that it may be excreted into the bile
Overexpression of MDR-1 can do what in cancer cells?
chemotherapy agent is pumped out of the cytosol as soon as it gets there, the drug never makes it to the nucleus to induce cytotoxic effects, thus leads to cancer cell resistance
What are some MDR-1 targeted interventions?
RNA interference, noncompetitive inhibitors, and competitive inhibitors
What is RNA interference of MDR-1?
silences the gene encoding MDR-1 by eliminating its mRNA
What genetic disorder is involved with MDR-2?
Dubin-Johnson syndrome
What occurs in Dubin-Johnson Syndrome?
MDR-2 is defective due to mutations in the ATP-binding region leading to impaired transcription and mislocalization of the MDR-2 protein (benign condition)
What are aquaporins?
protein channels for water
How are aquaporins controlled?
ADH (anti-diurectic) receptors that respond to ADH to increase amount of water reabsorption via translocation of aquaporins
What is cystic fibrosis transmembrane conductance regulator (CFTR)? What does it regulate?
chloride channel that regulates Na+ and HCO3
How do CFTR work in sweat glands?
CFTR allows chloride to move from sweat ducts back into cells, and eventually into the blood; this assists the movement of sodium into the cell due to electrostatic attractions (Cl- attracts Na+)
How do CFTR work in airways, bile duct, pancreas and intestines?
chloride moves out of epithelial cell via CFTR and into mucus; this encourages water to stay in the mucus, and gives it fluid-like properties
What occurs in cystic fibrosis that causes salty sweat?
lack of CFTR inhibits reabsorption of chloride from sweat duct that also inhibits movement of sodium
What occurs in the lungs for patients with cystic fibrosis?
defective CFTR causes the inability of chloride to be moved out of epithelial cells. The buildup of chloride ions also encourages more sodium ions to be moved into the cell from the mucus, bringing water along with. The mucus then becomes thickened and harder to move and becomes a breeding ground for bacteria
What occurs in pancreatic ducts and bile ducts if CFTR is defective?
obstruction due to the thickened mucus
What occurs to ductus deferens if CFTR was defective?
(sperm duct) becomes obstructed due to the thickened mucus
What is lactase and what is its function?
membrane associated enzyme (protein) that functions to break down lactose
What are dystroglycans?
structural proteins associated with striated muscle
What are dystrophins?
structural proteins found within muscle cells that link dystroglycans to other structural components within the cell. It gives striated muscle cell membranes strength and structure
What occurs in Duchenne and Becker muscular dystrophy?
mutations occur within dystrophin genes, thus compromising the integrity of the membrane. The insides of the cells are spilled out, muscle mass is lost
Where are glycolipids found?
exclusively in the noncytosolic lipid monolayer. some are found in intracellular membranes
What is the clinical significance of GM1 ganglioside?
it is a glycolipid that acts as a receptor for cholera toxin. Ultimately causes diarrhea due to loss of chloride ions
What are the vesicular transport processes?
endocytosis
excytosis
porocytosis
exosomes
What are the 5 pathways of endocytosis?
macropiocytosis clathrin-mediated non-coated-mediated caveole-mediated phagocytosis
