Final shit Flashcards
opening of the activation gate of a sodium channel likely corresponds to a ______
hinge-like motion of the S6 segments around a conserved glycine
The inactivation gate of NaV channels is formed by the ______
cytoplasmic loop which connects repeats III and IV
for nonmyelinated fibers, conduction velocity increases as the _________,
Square root of the diameter
Demyelination of axons results in proliferation of ____
sodium channels
The signal recognition partivle binding pocket is lined by ____
methionines
AA sequence that leads to N-linked glycosylation
Asn-X-Ser/Thr (X can be any amino acid except proline)
ER resident proteins have a specific ____ sequence on their _____, which binds to _______. These membrane proteins bind to _____
KDEL
KDEL receptors
COPI coats
Mannose 6-phosphate is a sorting signal for_______
Lysosomal proteins
Location of proteosome
cytosol and nucleus
E1
Activation
E2
Conjugation
E3
Ligation
Ubiquitin is added to ___
Lysine acceptor
Beta substrates of proteosome
proteolytically active
alpha subunits of proteosome
regulate substrate entry into death chamber
How does E. coli stay alive in a cell?
Glycosylate FADD, making it unable to activate Caspase 8
PKA phosphorylation effect on smooth muscle
inhibits smooth muscle contraction
Effective buffering occurs in the range from
[A-]/[HA] = 0.1 to 10 or within one pH unit on either side of the pKa
H-H equation for bicarbonate system
pH = 6.1 + log [HCO3-]mM/ .03Pco2mmHg
pH = 6.1 + log 24 mM/ .03 X 40mmHg pH = 6.1 + log 24/ 1.2 pH = 6.1 + log 20 = 7.4!
• Events that can produce loss of heterozygosity
o 1) Mitotic recombination
o 2) Loss of chromosome or translocation
P53 is inactive when bound to ____
mdm2
Systemic therapy of renal cell carcinoma
VEGFR-R inhibitors
tyrosine kinase inhibits
MTOR inhibitors
immunotherapies
Negatively charged lipids and location
PS, PI, PE
internal surface
GPI linkage location
Extracellular face
Regulated Intramembrane Proteolysis
o Cleavage of bHLH from SREBP sometimes cuts in transmembrane domain
o Critical for Notch signaling and development
o Important for cleavage of APP protein to produce B-amyloid peptide in Alzheimer’s disease
Proteins involved in RIP of bHLH
S1P and S2P
Two step protellysis
) HIV - Gp41 protein mechanism
Brings transmembrane domain and fusogenic pepetide domain close together fp imbedded into membrane
Regulation of specificity for viral fusion comes at the ___ level
Activation
Influenza viral fusion mechanism
- Binds plasma membrane of any cell, and gets internalized into lysosome
- Drop in pH of lysosome triggers activation of influenza
- Stable metastable conformation triggered by low pH
- Not cell specific, but timing specific
HIV viral fusion mechanism
- Fuses with plasma membrane and GP41 and GP120 recognize and binds to CD4 change conformation activating GP41
- Regulated by binding to CD4 receptor HIV only recognizes CD4 containing cells
Donnan rule
[K+]o [Cl-]o = [K+]i [Cl-]i
Describe why, in neurons and other excitable cells, membrane potential is sensitive to small changes in [K+]o, but not [Na+]o.
o Cell is more sensitive to [K+] because its starting concentration outside the cell is much smaller than Na+, and thus is much more sensitive to small changes in concentration
People at higher risk for cerebral edema in DKA
Sicker or younger
Clinical manifestation cerebral edema
Hypertension
Bradycardic
Tight epithelia location
Sweat glands, distal kidney tubules
Leaky epithelia locations
small/large intestine, gall bladder, proximal kidney tubules
pumps involved in epithelial secretion
- Na/K/2Cl cotransporter- basolateral side
- Cl- channel- apical side
Myelin ____ electrical resistance and ____ capacitance
increases
decreases
Consequences of demyelination in MS
- Change resting potential
- harder to depolarize due to constant leak of K+ out of cell
- Produce proliferation of Na channels
Therapies for MS
- NA channel blockers
- K+ channel blockers
Na channel blockers for treatment of MS
Phenytoin, Flecainidine
Preserve axons
K channel blockers for treatment of MS
Dalfampridine
Signal Recognition Particle (SRP) is made of
6 proteins and 1 RNA
What happens after the proteasome cuts off the ubiquitin?
Ubiquitin is recycled
B1 – cleaves after _____
B2 – cleaves after ____
B5 – cleaves after _____
Acidic AA
Basic AA
Hydrophobic AA
Microtubule polymerization inhibitors
Colchicine, vinblastine, vincristine
o Paclitaxel
binds and stabilizes microtubules causing Tubulin aggregates block mitosis
Arp2/4 _____ two actin monomers
FH2 ____ two actin monomers
Mimics
Binds
• Lissencephaly
Severe brain development defect, smooth cortical surface (no gyri)
oNormal complex cytoarchitecture requires neuronal migration
o Due to loss of function n-coflilin (actin filament depolarizing
Three main sources of androgen in PCA
-testes 90-95
adrenal glands 5-10
intracrine androgen production
4 mechanisms of resistance to hormone therapy in PCA
1.ARactivationvianon‐gonadaltestosterone 2.OverexpressionofAR 3.ARmutationleadingtopromiscuousAR activation 4.TruncatedformofAR,withconstitutive activationoftheligandbindingdomai
Enzyme that plays a key role in androgen production
CYP17
Specific inhibitor of CYP17
Abiraterone
blocks test from all three sources
Enzalutamide
antiandrogen
Enzalutamide inhibits: (3)
- nuclear translocation
- co activator recruitmen
- DNA binding of AR
