Exam 4 Flashcards
Biological membranes are __layers
bilayers
What are biological membranes made of?
lipids and proteins
(sometimes glycolipids/glycoproteins)
What are 3 important properties of biological membranes?
- fluid (lipid/protein migration occurs)
- mosaic (not uniform)
- asymmetric (two layers are not the same)
Why are membranes arranged into a bilayer?
their lipids are amphipathic
What are the 4 types of membrane lipids?
- phospholipids
- glycolipids
- sterols
- ether lipids
What are the possible backbones of phospholipids?
glycerol or sphingosine
(glycero-phospholipids or shingo-phospholipids)
What are the possible backbones of glycolipids?
glycerol or sphingosine
Do humans have ether membrane lipids?
no (archaebacteria)
How many carbons is a glycerol backbone?
3
How many carbons is a sphingosine backbone?
18
How many tails do glycero-phospholipids have?
2
How many tails do sphino-phospholipids have?
1
What determines the function of a phospholipids?
functional group added to the head of lipid
Some glycero-phospholipids have _____ linkage at C1 position of glycerol
ether
On glycero-glycolipids, the C3 is linked to _________ instead of a phosphate group (like phospholipids)
galactose
What kind of membrane lipid is most common especially in plants?
glycero-glycolipids
What glycolipids is abundant in the brain and nerve tissue?
sphingo-glycolipids
What membrane lipid is a derivates of ceramides?
sphingo-glycolipids
What do sterols look like?
4 fused carbon ring
What is the major sterol in humans?
cholesterol
What is special about ether lipids?
resistant to high temperatures and extreme pHs
Lipid composition of membranes depends on their __________
function
Phophatidycholine and sphingomyelin are mainly in the ______ monolayer
outer
Phosphatidyl serine and phosphatidylinositol are mainly in the _______ layer
inner
What is a flippase?
flips lipids from outer to inner
What is a floppase?
flips lipids from inner to outer
What is a scramblase?
can flip lipids outer to inner and vise versa
Why don’t lipids flip bilayers often?
the polar head has to pass through the non-polar tail region which is no favored
What is a hypotonic environment?
(cell swells)
more salt inside the cell so water flows inside the cell
What is a hypertonic environment?
(cell shrivels up)
more salt outside the cell so water flows out of cell
At low temperatures, bilayer lipids are ______ forming a gel phase called ______-______ state
ordered
solid-ordered state
At high temperatures, bilayer lipids are _______ forming a ________-_______ state
moving
liquid-disordered state
Membranes with cholesterol have a 3rd possible state known as _____-_______ state, which is where lipids are moving but ordered
liquid-ordered state
Membranes have _______ enriched with specific lipids and proteins
microdomains
Membranes that carry out many enzyme-catalyzed reactions and transport activities are richer in __________
proteins (ex: mitochondria inner membrane)
What are the 3 types of membrane proteins?
- integral
- peripheral
- lipid-anchored
What kind of membrane protein is embedded in the membrane?
integral
What kind of membrane protein is transmembrane?
integral
What kind of membrane protein cannot be released without denaturing the membrane?
integral
What kind of membrane protein is not strongly bound to membrane?
peripheral
What kind of membrane protein can be detached with mild detergent and high salt?
peripheral
What kind of membrane protein are temporarily anchored?
lipid-anchored
What is the hydrophobicity index?
value assigned to each amino acid residue to determine hydrophobic to find transmembrane regions of proteins
(higher the number the more hydrophobic)
Do antibiotics target high or low hydrophobicity index regions?
low (outside the membrane)
Why are beta sheets used in membrane proteins?
don’t require as much genetic material
What kind of interaction bind peripheral proteins to membrane?
ionic (can be disrupted by salt)
What kind of interaction bind lipid-anchored proteins to membrane?
covalent bonds (not affected by salt)
What are 2 types of lipid-anchored proteins?
- amide-linked myristol anchors
- GPI anchors
Where are amide-linked myristol anchors located?
N terminal (beginning)
What are amide-linked myristol anchors always linked to?
Gly residue
Where are GPI anchors located?
C terminal (end)
What direction do GPI anchor proteins face?
outside the cell
Integral membranes proteins with ______ shape can induce curvature
conical
What is required for diffusion to occur?
concentration difference
Select the correct transport(s)…
goes down the concentration gradient
passive
facilitated
Select the correct transport(s)…
requires transport proteins
facilitated
active
Select the correct transport(s)…
requires ATP
active
Select the correct transport(s)…
transports small non-polar molecules
passive
Select the correct transport(s)…
goes up the concentration gradient
active
Select the correct transport(s)…
does not require transport proteins
passive
Select the correct transport(s)…
does not require ATP
pasive
Select the correct transport(s)…
transports large/polar/charged molecules
facilitated
active
Select the correct transport…
transports O2 and steroids
passive
Select the correct transport(s)…
transports Cl-, Na+, H2O
facilitated
Select the correct transport(s)…
glucose, histidine
active
How does reaching equilibrium change when the passive diffusion molecule has a charge?
the concentrations may be different because of the potential differences
Is the delta G positive or negative for facilitated diffusion?
negative (thermodynamically favored)
Why does facilitated diffusion have a hyperbolic curve?
its faster at lower [ ]s and levels off at higher [ ]s because the proteins become saturated
What are 5 types of pores/channels?
- ionophores
- porins
- ion channels
- aquaporins
- transporters
What are ionophores used for?
used to kill bacteria (not in humans)
____ channels can be opened and closed upon signals
ion channels
What are uniports?
transport one thing one way
What are symports?
transports two things one way
What are antiports?
transports 2 things in opposite directions
Potassium channels are highly selective of K+, how?
specific highly conserved AA sequence at entrance of channel
How many subunits does a potassium channel have?
4
How is K+ transported through the potassium channel?
in a line with H2O between each K+ to prevent repulsion
Potassium channel is gated by intracellular ____ meaning _____ is the entrance signal
pH
H+ (protons)
Potassium channels are open at ______ pH and closed at ______ pH
open: low pH
closed: neutral pH
What is a primary active transporter?
use ATP as an energy source
What are examples of secondary active transporters?
symporters and antiporters (use electrochemical gradient)
What is an example of a primary active transporter?
sodium/potassium pump
How do Na+/K+ pumps maintain the negative intracellular cellular charge?
pumping 3 Na+ out and 2 K+ in (-1 inside)
What is the energy source of Na+/K+ pumps?
ATP hydrolysis
What are the 2 conformations of Na+/K+ pumps?
open to inside (E1)
open to outside (E2)
Why do Na+/K+ pumps have 2 conformations?
prevents ions from freely traveling in and out of cell
What are the 4 domains of Na+/K+ pumps?
N (nucleotide-binding)
A (actuator)
P (phosphorylation)
T (transport)
What domain does K+ bind to in Na+/K+ pumps?
T domain
What is endocytosis?
transport into cell via vesicle
What is exocytosis?
transport out of cell via vesicle
What is CFTRs function?
Cl- channel
Where is Cl trying to go in cystic fibrosis?
out of the cell but it cannot
Cystic fibrosis is the impairment of _____ transport
Cl-
What is juxtacrine signaling?
signaling between adjacent cells
What is paracrine signaling?
short distance signaling (cytokines)
What is endocrine signaling?
long distance signaling (hormones)
What are 2 examples of juxtacrine signaling?
gap junctions
membrane-bound ligands
What are gap junctions?
(juxtacrine signaling) connexins connect 2 cells allowing ions the flow
What is signaling by membrane-bound ligands?
(juxtacrine signaling) direct contact between cell 1 ligand and cell 2 receptor
_________ are signaling molecules that bind specifically to a receptor
ligands
What is a ligand-gated ion channel?
ion channels that open upon binding of ligand (ion)
What is an example of a ligand-gated ion channel and what was its ligand?
K+ channel (H+ ligand; low pH intracellular environment)
Ligand gated ion channel have _____ distinct conformations. Why?
2
prevents ions from freely going where ever
What is the special 3rd conformation of ligand-gated ion channels?
desensitized (won’t open even if ligand binds)
Where are nuclear hormone receptors located?
in cytosol or nucleus
** inside cell
What kind of ligands do nuclear hormone receptors use?
non-polar (must get inside of cell easily to get to receptor)
What do type I nuclear hormone receptors look like ligand bound and unbound?
unbound: monomer
unbound: homodimer
What is an example of a type I nuclear hormone receptor?
estrogen
Estrogen receptor has a ton of functions, how is this possible?
uses co-activators and co-repressors for transcription
What’s the largest family of cell surface receptors and is a major drug target?
GPCR
How many domains does GCPR have?
7
Are GCPR integral proteins?
yes
In GPCR, binding of ligand to GPCR induces a conformational change that activates ___________
G-protein
G-alpha protein interact with ______ and binds ______
GCPR
GTP/GDP
G-alpha+gamma are ________ anchored
lipid anchored (need to be able to move near receptor which is integral)
G protein is active when ____ is bound and inactive when ____ is bound
GTP
GDP
What is GAP? (GPCR)
increases GTPase activity
(GTP hydrolysis)
What is GEF? (GPCR)
promotes exchange of GDP to GTP
What are the 3 subunits of the G-alpha trimeric protein?
- Gs
- Gi
- Gq
trimeric Gs protein activates _________ which increases ________
adenylyl cyclase
cAMP
trimeric Gi protein inhibits _________ which decreases _________
adenylyl cyclase
cAMP
What makes cAMP?
adenylyl cyclase
cAMP, Ca2+, IP2 and DAP are examples of?
secondary messengers
___________ is the main mediator of cAMP signaling
protein kinase A
(cAMP–>PKA—>gene effect)
Activated Gq trimeric protein activates ___________
phospholipase C-B
Activated phospholipase C hydrolyzes ______ which yields ______ and _____
PIP2
IP3 & DAG
What is the fate of DAG once its made from PIP2?
stays in membrane and activates protein kinase C
What is the fate of IP3 once its made from PIP2?
diffuses into cytosol and induces release of Ca2+
How is the GPCR signaling termianted?
arrestins bind to phosphorylated receptor preventing G protein from binding
What happens to GPCR after arrestins bind?
receptor is endocytosed and can continue to signal
Where is adenylyl cyclase located?
membrane
NOTCH signaling is a highly ______ pathway
conserved
What are the ligands for NOTCH?
JAG and DLL
How many types of NOTCHs are there in mammals?
4
What is an example of proteolysis regulated receptors?
NOTCH
Where is notch located?
membrane
What activates NOTCH receptor?
binding of ligand and cleavage
Why is NOTCH cleaved?
can enter nucleus
What is NOTCH important for?
cell fate
Is notch contact or paracine signaling?
contact
Are hormones a ligand for NOTCH?
no (contact signaling)
How many times can you activate NOTCH?
once (its cleaved)
IP3 causes the release of _____
calcium
enzyme linked receptors have how many transmembrane domains?
1
Receptor tyrosine kinase is an example of what kind of receptor?
enzyme linked receptor
What kind of receptor is receptor-like tyrosine phosphatase?
enzyme-linked receptor
What is the intracellular part of receptor tyrosine kinase?
tyrosine kinase
On the receptor tyrosine kinase, binding of the ligand activates ______________ domain
tyrosine kinase
receptor tyrosine kinase is __________ when inactive and ________ when active
monomer
dimer
When receptor tyrosine kinase dimerizes what happens?
autophosphorylation
Phosphorylated tyrosine kinase on RTK acts as a _________ for intracellular signaling proteins
docking site
proteins that use receptor tyrosine kinase but don’t have SH2 or PTB domains rely on _________ to create a docking site to bind to receptor
scaffolding protein
What are the 3 possible pathways for receptor tyrosine kinase?
1, MAPK
2. PI3K
3. PLC
MAPK pathway has _____ kinases in succession
3
What is the first kinase in the MAPK pathway?
Ras (monomeric G protein)
How is Ras connected to membrane?
lipid anchored
Ras is the GEF for monomeric G proteins. What is the GEF for trimeric G proteins?
the GPCR
What kind of kinase is used in PI3K pathway?
lipid kinase
In the PLC pathway, _________ is cleaved into ______ and _______
PIP2
DAG & IP3
What pathway of receptor tyrosine kinase uses G proteins?
MAPK (monomeric G protein
What does Ras GEF do in receptor tyrosine kinase?
exchanges GDP for GTP
How does receptor tyrosine kinase use localization in MAPK pathway?
moves Ras GEF closer to receptor for activation
How is MAPKK a dual specificity kinase?
can phosphorylate tyrosine and threonine/serine
_____ domain of receptor tyrosine kinase binds specifically to phosphorylated tyrosine residues
SH2
_____ activates a downstream serine/threonine phosphorylation cascade that includes MAP kinase
Ras
In the PI3K pathway, PIP3 —-> _____ —–>
AKT
mTORC1
What does PTEN do in the PI3K pathway?
dephosphotylates PIP3 to stop signaling
PI3K is a major pathway in cell _____________
growth/survival
What is made in the PLC-g pathway?
IP3 and DAG
What is a signaling pathway used by tyrosine kinase associated receptors?
JAK/STAT
What is STAT?
transcription factor
How is the JAK/STAT pathway terminated?
dephosphorylation of STAT and JAK
What is the ligand for receptor-like tyrosine phosphatase?
unknown
The _____________ domain of receptor serine/threonine kinase is serine and threonine kinase
intracellular
What is an example of a receptor serine/threonine kinase signaling pathway?
TGF-B
In TGF-B signaling, ligand first binds to type II receptor then type ____
type I
Activated receptor serine/threonine kinase in the TGF-B signaling pathway recruits ________
Smads
What is the secondary messenger for receptor guanylyl cyclase?
cGMP
The secondary messenger, cGMP, of receptor guanylyl cyclase activates ______ and _______
Protein kinase G
cGMP Ca2+ channel
Can signaling pathways combine?
yes
Do some reponses require activation of multiple pathways?
yes
Steroid hormones, such as cortisol, typically act by entering the cell and binding to receptor or binding on cell surface?
entering cell and acting as transcription regulators
The endogenous GTPase activity of G-proteins serves to hydrolyze ______, returning the G-protein to a pre-stimulation level of activity
GTP
What’s the difference between a channel and a transporter?
transporters are never full open (they have 2 conformations)
channels are just a hole that opens
For receptor tyrosine kinase, proteins that have ____ and ____ domains can bind to tyrosine docking site
SH2
PTB
Most glycolipids in mammals is derived from _______
ceramides
Can simple diffusion be saturated?
Can facilitated diffusion?
simple: no
facilitated: yes
