Midterm 2 Flashcards
(111 cards)
1
Q
What are the parts of the membrane bilayer? And what dimension does it fall into?
A
Made up of fatty acids, lipid head groups, and water molecules. The membrane bilayer is a two-dimensional fluid
2
Q
What are the different phospholipid movements in the bilayer and what do they do?
A
- Lateral diffusion: movement of the heads
- Flexion: movement of the tails
- Rotation: rotation of head and tail
- Flip-Flop: flip flop of one side to the other
3
Q
What are the types of diffusion of a phospholipid fluid bilayer? Describe them
A
- Lateral diffusion of lipids is fast and favourable
- Transbilayer diffusion of lipids is slow and unfavourable
- Many different ones. The lateral diffusion of each of the lipids is different
4
Q
Why do membranes differ in composition? What are the different properties?
A
- Composition affects functions and properties
- saturated phospholipids = more rigid VS unsaturated = more fluid
- Higher cholesterol content = better packaging of phospholipids = more ibid and reduced water permeability
5
Q
What happens to fluid-like membranes?
A
They can form domains meaning the bilayer is not uniform
6
Q
What are membrane rafts?
A
Parts of the membrane enriched in specific lipids: saturated lipids, cholesterol
7
Q
Why do saturated lipids fit better together? What do unsaturated lipids vs saturated lipids and their chains look like?
A
Because they pack better together they have better van fed waals attraction. They spend more time together than with unsaturated lipids
8
Q
Answer the blank. The membrane buoyant leaflets are……
A
Asymmetric
9
Q
What is apoptosis and glycolipids asymmetry?
A
- loss of PS asymmetry leads to programmed cell death = apoptosis
- glycolipids asymmetry responsible for blood types
10
Q
What are the membrane proteins and their functions?
A
- Overall each cell surface proteins give identity to cells, regulates attachment, shape and motility of cells
- Receptors: Binds specific ligand molecule to one side of the membrane and transmits this interaction/info to the other side. Usually this is an outside to the inside of the cell flow
- Channels: Allows diffusion of ions and small molecules
- Transporters: Couples energy of ATP or gradient to transport molecules against a gradient
- Signalling Molecules: Variety of molecules that are attached to membranes to regulate cell function
11
Q
What are transmembrane proteins? What do transmembrane proteins 1-5 do? What do hydrophobic portions do?
A
- membrane proteins that cross the bilayer. They are amphipathic.
- Hydrophobic portions are inserted into the membrane and interact with hydrophilic tails of phospholipids: transmembrane domains. Hydrophilic portions are exposed to aqueous environment
- transmembrane proteins (1-5) permit communication across a membrane
12
Q
How do proteins associate with membranes? What does proteins (7-10) look like and what do they do? What are the names of the proteins and their functions?
A
- Lipid anchored proteins: covalentes modified proteins with lipids
- Peripheral membrane proteins: proteins- bind non covalently to transmembrane and/or membrane lipids
13
Q
Know what three types of covalently attached lipid anchors look like in inner leaflet and how to describe them. What are their names?
A
- myristoyl anchor
- paimitoyl anchor
- farnesyl anchor
14
Q
Integral vs peripheral membrane proteins, what do they look like? How do they work?
A
- integral membrane proteins (1-8) are strongly held to the membrane
- only detergents can remove these proteins from te membrane
- peripheral membrane proteins (9-10) are held by weak interactions ( ionic & hydrogen bonds)
- dissociated by changes in pH, salt
15
Q
Most transmembrane proteins _______________
A
Cross the membrane as a hydrophobic a-helix
16
Q
Hydrophobic amino acids are shown as what colour?
A
Green
17
Q
How long are hydrophobic a-helix?
A
20-30 amino acids long
18
Q
How can hydrophobicity be measured?
A
In a hydropathy plot
19
Q
What do hydropathy plots look like? What do the positive and negative values mean?
A
- positive: not favourable, hydrophobic
- negative: favourable, hydrophilic
20
Q
What’s bacteriorhodopsin?
A
A seven transmembrane a-helix protein in bacteria. Example os structure and function of a transmembrane protein
21
Q
What does bacertiorhodopsin do? What does it look like? How does it work?
A
- captures light and pumps H+ across the bacterial plasma membrane
- Establishes a H+ gradient to drive ATP production
- covalently modified by retinal, which captures photons
- photons change retinal shape
- causes H+ to hop in the sequence shown(orange numbers)
- result is net movement of H+ across membrane bilayer
22
Q
Many plasma membrane proteins are. ______________
A
Glycosylated and have disulphide bonds
23
Q
What are disulphide bonds? What do they do? Where do they form?
A
- Cysteine amino acid residues react to each other to form sulphur to sulphur bridges
- they help to stabilize protein shape
- they form in extra cellular space (not cytosol)
24
Q
What’s glycosylation? Where are most plasma membrane proteins glycosylated? What does it look like?
A
- covalent addition of oligosaccharides to proteins
- serine or asparagine residues
25
What’s the glycocalyx? What’s it made from? What is its function?
- The cell surface coat of glycosylated proteins
- made from glycosylated proteins
- allows cells to adhere to the matrix and to other cells. Gives identity to cell types
26
What are integral membrane proteins? How do they interact with the lipid bilayer?
they insert part of their amino acid sequence into the lipid bilayer and are permanently part of the membrane
27
What are lipid-anchored proteins? How do they interact with lipid bilayers?
are covalently attached to a lipid, and the lipid
is embedded in the membrane (mostly permanently part of membrane)
28
What are peripheral membrane proteins? How do they interact with lipid bilayers?
protein associates by non-covalent
interactions with integral membrane proteins or lipids, is non-permanently part of membrane
29
What are one examples of membrane proteins?
Bacteriorphodopsin and glycophorin
30
What does FRAP look like? What does it determine?
It can determine lateral diffusion of membrane proteins
31
What are the 3 types of lateral diffusion of membrane proteins?
1. Free or unrestrained diffusion
: a protein can freely move across the plane of the membrane; FRAP: rapid recovery of fluorescence
2. No or negligible diffusion: a protein is completely immobile or it’s diffusion is slow; FRAP: slow to no recovery of fluorescence
3. Restricted or partial diffusion: a protein is free to diffuse but only within a subsection of a membrane
32
What’s an example of limited diffusion? What does it look like?
- Polarized epithelial cells(intestine)
- one side of the cell
faces to the
outside world, the
other side faces to
the inside of the body
33
Dividing the membrane…….. A&B What does it look like? What is separation done by?
- the apical and basal membrane in epithelial cells
- Apical and basal membranes are contiguous but are distinct in composition and function
- separation is done by a dense structure called the tight junction
34
Dividing the membrane….. sperm cell? What does it look like? Antibodies?
- the sperm cell has three plasma membrane sub-domains
- Antibodies to three different sperm
membrane proteins stain three
different sperm membrane regions
35
What are the mechanisms to restrict membrane protein movement?
- self-assemble into large complexes
- tethered to the cytoskeleton inside cells
- tethered to the extracellular matrix
- interact with proteins on another cell
36
What is the shape of red blood cells and what is it due to?
It’s a biconcave shape and it’s due to membrane protein interactions with a cortical cytoskeleton
37
What’s spectrin? What does the spectrin cortical cytoskeleton do and where is it found? What’s glycophorin and band 3? What does everything look like? What is the spectrin cortical cytoskeleton? How are spectrum filaments attached? Whats the junction and complex? What’s the function? Explain
- a protein similar to actin that forms a mesh like structure under the plasma membrane
- the spectrin cortical cytoskeleton of red blood cells interacts with membrane proteins
- glycophorin and band 3: two different integral membrane proteins that bind spectrin, link skeleton to membrane
- the spectrin cortical cytoskeleton of red blood cells interacts with membrane proteins
- the spectrin cortical cytoskeleton is a filamentos mesh work underneath the cytosolic face of the plasma membrane of the red blood cells
- spectrin filaments are attached to the membrane by interaction with ankyrin and the band 3 transmembrane protein
- multiple spectrin filaments are cross-linked by the junction along complex
The junctions, complex includes filamentous actin and it is attached to the membrane by the transmembrane glycophorin protein
- FUNCTION: give the red blood cells some shape and structure that is still flexible
38
What is the cortical actin cytoskeleton? What does it look like?
The cortical actin cytoskeleton is like a wide mesh frame for a red blood cell
39
What do cortical cytoskeleton do? What does it look like?
Creates membrane domains that restricts protein diffusion
40
What are the different mechanisms by which restricted membrane protein diffusion can occur?
- proteins are restricted within small corrals (200-400nm)
- proteins are restricted from moving between apical and basolateral membranes in epithelial or endothelial cell layers
- proteins are restricted in different sections of the cell surface in sperm cells
41
How many membrane proteins are free to diffuse throughout the entire cell membrane?
Only a few
42
Function of epithelial cells?
Directional nutrient transport
43
Function of sperm cells?
Movement and encapsulation of DNA
44
Function of red blood cells?
Maintaining shape, flexibility and more
45
What’s the importance of the cell cycle? What does it look like?
Regulation of cell division is required for growth, development, and tissue renewal
46
What are the stages of the cell cycle?
- G1
- S
- G2
- M
47
What are the stages of M-phase? What’s included in mitosis? Where do they occur?
- prophase
- prometaphase
- metaphase
- anaphase
- telophase
- cytokinesis
- mitosis = prophase, metaphase, prometaphase, metaphase, anaphase, and telophase
- all M-phase stages occur in G2
48
What happens in the G1 phase?
Preparation of cell for DNA replication
49
What happens in the S phase?
DNA replication
50
What happens in the G2 phase?
Cell growth(size, biomass, materials)
51
What happens in the M phase?
- sorting of materials (chromosomes, organelles) in preparation for separation
- separation of the cell into two daughter cells
52
M-phase 1:prophase what does it look like? What does it do?
- chromosomes begin to condense
- mitotic spindle begins to assemble
53
M-phase 2: prometaphase what does it look like? What does it do?
- breakdown of the nuclear envelope
- attachment of the chromosomes to the spindles (microtubules)
54
M-phase 3:metaphase what does it look like? What does it do?
- alignment of the chromosomes at the equator (site at which the cells will eventually separate)
55
M-phase 4:anaphase what does it look like? What does it do?
- sister chromatids (copies of the same chromosome separate)
- chromatids are pulled apart towards the spindle poles
56
M-phase 5:telophase what does it look like? What does it do?
- the full set of daughter chromosomes arrive at the spindle poles
- a contractile ring begins to form that starts to pinch the cytosol at the site that the cells will eventually separate
- nuclear membrane begins to reform
57
M-phase 6:cytokinesis what does it look like? What does it do?
- a contractile ring squeezes the cell to form two daughters
- once fully contracted this generates a cleavage furrow which represents the final stage of separation of the two daughter cells
58
What are the 3 distinct checkpoints/regulation points in the cell cycle? What does it look like?
- G1/G0 cell cycle start
- G2/M checkpoint
- Metaphase-to-anaphase transition
59
What is the cell cycle controlled by?
- cyclin-dependent kinases(Cdks)
60
What do cycling-dependent kinases do?
- cyclin-dependent kinases can phosphorylate several different substrate proteins
- phosphorylation of proteins by Cdks acts as a switch to progress through specific stages of the cell cycle
- the switch mechanism that turns Cdks on is binding to one of the several specific cyclin proteins
-cycling not only activated Cdks but also target Cdks to specific substrates
61
The levels of specific cycling rise and fall at specific stages of the cell cycle. True or false? What does the diagram look like?
True
62
Do Cdk levels change deputing the stages of the cell cycle?
No they do not change
63
How does M-Cdk control G/M transition? What does the activation of M-Cdk cause?
- M-Cdk activation triggers condensin (protein complex), which causes condensation of chromosomes
- M-Cdk activation causes formation of the mitotic spindle
64
What starts mitosis?
M-Cdk activation
65
What finishes/completes mitosis
The removal of M-Cdk
66
What is APC/C? What does it do?
-APC/C is a protein complex
- it’s required to allow metaphase to anaphase transition
- that leads to degradation (removal) of M-cyclin and loss of M-Cdk complexes
67
Why do Cyclin-Cdk complexes act like a timer? What does this allow Cyclin-Cdk to do? What does Cyclin-Cdk complexes allow for cell cycle checkpoints? What does this allow Cyclin-Cdk to do?
- it can allow degradation or removal of cyclin of the previous cell cycle stage
- it can cause upregulation of the cyclin of the next stage of the cell cycle
- Overall, this allows Cyclin-Cdk complexes to make sure that stages of the cell cycle don’t happen at the same time
- Cyclin-Cdk complexes can be controlled (eg turned off ) if conditions of the cell cycle aren’t met: damage, insufficient nutrients, insufficient growth factor stimulation, failure to complete previous stage
- Over, all Cyclin-Cdk complexes to monitor to make sure moving to the next stage of the cell cycle is safe
68
Are Cdks used in medicine? Which ones? How?
- some Cdks are very effective cancer drug targets
- their used for treatment of metastatic breast cancer, pancreatic cancer, and other cancers
69
When does the mitotic spindle begin to assemble? What does it involve?
- In early mitosis
- begins in prophase
- involves microtubules, centrosomes (to anchor microtubules and many other proteins)
70
What is the mitotic spindle? What does it look like? What are the parts and their definitions?
- mitotic spindle: a bipolar array of microtubules involved in proper separation of chromosomes and other materials during mitosis
- spindle pole: made up of centrosome and other components, all three types of microtubules emanate/start from here
- Astral microtubules: from spindle pole to cell cortex helps anchor spindle poles
- Kinetochore microtubules: from spindle pole to chromosome (attaches kinetochore region of chromosome)
- interpolar microtubules: from spindle pole to interpolar microtubule coming from the other spindle pole
71
What is kinetochore? What do they look like?
A region of a chromosome made up of proteins that allow anchoring of spindle microtubules
72
What does mitotic spindle do? With what? What happens at transition from metaphase to anaphase
- positions chromatids for correct separation into daughter cells
- sister chromatids: identical copies of chromosomes that are held together during early stages of mitosis
- at transition from metaphase to anaphase: the glue that holds the sister chromatids together is removed and each sister chromatid is pulled towards one spindle pole
73
How does a cell know when it is time to proceed from metaphase to anaphase?
- in metaphase all chromosomes need to be attached to kinetochore microtubules to prevent improper sorting of chromosomes during cell division
- thus can be sensed by making sure that all kinetochores are attached to microtubule
- this is the metaphase to anaphase transition checkpoint
74
What are drugs targeting the mitotic spindle assembly effective cancer therapies? How do they work?
Paclitaxel, docetaxel
- chemotherapies used in many types of cancer treatments
- these work by binding and stabilizing microtubules, prevents assembly of mitotic spindle
- trigger metaphase -anaphase checkpoint arrest
75
Why are drugs that alter microtubules filament assembly effective cancer therapies?
They trigger cell cycle arrest in mitosis, by impairing assembly of the mitotic spindle
76
Permeability of protein-free lipid bilayers, what do they look like? What is membrane permeability?
- membrane permeability is inversely proportional to size, polarity and charge
- most charged or polar = less permeable
- larger = less permeable
- cells need a mechanism to move ions across the membrane. This is accomplished by transport proteins
77
Why does the cell need mechanisms?
To allow specific molecules to cross the membrane barrier: membrane transport proteins
78
What are membrane transport proteins?
Specific for one or a few types of molecules. All membrane transport proteins are multi pass integral membrane proteins. There are two types, channels and carriers/permeases
79
What do membrane carrier/permease proteins and membrane channel proteins look like?
- membrane channel proteins forms a continuous pore. Channels must be open or closed so there needs to be a gating mechanism
80
What’s passive vs active transport?
- passive=downhill, spontaneous (negative delta G). Diffusion down gradients-no energy needed
- active = uphill, not spontaneous (positive delta G) requires energy input. Energy required
81
What happens during the passive transport of charges solutes? What is the electrochemical gradient? What is the electrical potential diiference?
- the electrochemical gradient is the net driving force that consists of concentration and electrons potential difference
-movement of a charged molecule follows the electrochemical gradient
- the electrical potential difference across a membrane is called the membrane potential
82
What happens to a transporter during passive transport? Where are transporters found? What does switching between the two states do?
- transporters exist in two conformational states open to different sides of the membrane
- switching between the two states does not depend on solute concentration, movement of solute simply depends on electrochemical gradient
83
What is active transport?
- transport is against the concentration gradient
- requires energy
- active transport is catalyze by transporters know as pumps
84
What kind of molecules can diffuse across lipid bilayers?
Small, non polar,uncharged molecules
85
What happens when polar molecules diffuse?
They move slowly across lipid bilayers, the diffusion is still slow for molecules with increased size or charged
86
What is the net diffusion determined by?
The chemical gradient (uncharged molecules) or the electrochemical gradient (charged molecules)
87
What is facilitated diffusion carried out by?
By proteins called carriers (permeases, transporters)
88
Explain the mechanisms of facilitated diffusion
Involves a carrier protein flipping between inward- and outward- facing conformation; switching between these states does not depend on solute concentration or binding
89
What do the three mechanisms used by transporter pumps to drive active transport look like? What are they?
1. Coupled transporter, energy comes from electrochemical gradient of other molecule
2. ATP-driven pump, energy from ATP hydrolysis
3. Light-driven pump, energy from light
90
What does a transport pump do?
Couples movement of molecules against their electrochemical gradient with a source of energy
91
What’s a symporter?
Transport of molecule A(unfavourable) coupled to transport of molecule B(favourable) In the same direction
92
What’s a antiporter?
Transport of molecule A(unfavourable) coupled to a transport of molecule B(favourable) in the opposite direction
93
What does a coupled-transporter do?
Joins the movement of one solute species(A) against its gradient with the movement of another solute species(B) that diffuses along its gradient
94
Which species is transported actively and passively diffused? Species B is the source of what?
- species A is actively transported
- species B is passively diffused
- electrochemical potential energy
95
Explain the process of the plasma membrane Na+- glucose symporter. Where is it found? What is its function? What does it look like?
- The Na+-glucose symporter is
found in the plasma membrane
of epithelial cells in kidney and
intestines.
- Its function is to recover
glucose from extracellular
medium before excretion
- To transport glucose against this
concentration gradient, cells use the
strong electrochemical gradient of
Na+: [Na+]extracellular >> [Na+]cytosol
Outside cells
(intestinal lumen or urine)
Inside cells
(intestinal or kidney
epithelial cell)
96
What does asymmetric distribution of transporters in
epithelial cells allow for?
transcellular
transport of molecules
97
What happens during asymmetric distribution of transporters in epithelial cells? Na+/glucose transport? Glucose permeation? Na+/K+ pump?
- Na+/glucose transport
occurs at the apical side
(active transport)
- Glucose permeation (by
passive transport) on the
basal side allows glucose to
leave cells and go into
deeper tissues
- So, over time, Na+ enters the
cell and would build up
inside the cell except that
- Na+/K+-pump: reestablishes
Na+ gradient
- Na+/K+-pump occurs on the
basal side to avoid loss of
electrolytes (sodium) in the
urine/feces
98
What are ATP-Driven pumps(transport ATPases)?
Membrane transport enzymes that couple the energy released
by ATP hydrolysis to drive transport of solutes against their
electro-chemical gradient
99
What are the three types of ATP-driven pumps and transporter? What do they do?
- P-type pump:
transporters that self-phosphorylate, i.e., covalently transfer a phosphate
during ATP hydrolysis to itself as part of the transport cycle.
P-type pumps typically setup and maintain ion gradients across membranes
- F-type H+ pumps:
these are multi-subunit, turbine-like complexes found in bacteria,
mitochondria and chloroplasts.
use H+ gradients to synthesize ATP.
- ABC Transporter:
Uses ATP hydrolysis to pump small molecules across the membrane. Does
not get phosphorylated
- V-type H+ pumps:
related to F-type but use ATP hydrolysis to pump H+ against electro-
concentration gradient.
acidifies organelles.
100
What is the The P-type Na+-K+ ATPase
Pump?
[Cytosolic K+] is 10-30x > [extracellular K+]
[Cytosolic Na+] is 10-30x < [extracellular Na+]
High electrochemical gradient of
Na+ drives uptake of nutrients
like glucose and amino acids,
and regulates cytosolic pH
101
How does the model of P-type Na+-K+ pump work?
- Exchanges 3 Na+ to 2 K+
- electrogenic drives a net electrical
current across the
membrane
102
What is osmosis?
Osmosis: movement of water across a
semi-permeable membrane due to a
difference in water concentration
[water] changed by the number of
“particles” present in a solution
103
Hows the inside of the cell?
- has high osmolarity
- 1. Macromolecules are charged and require counterions to balance the charge.
2. Small metabolites charged and uncharged
3. Ions inside the cell
High intracellular osmolarity
Water flows into the
cell, causing swelling
and bursting
104
What does the P-type Na+-K+ Pump
control and how?
- osmolarity
- The Na+ electrochemical gradient
draws Cl- and balances the
intracellular and extracellular [solute].
Balances water movement
- if nothing is done it swells
105
What are ion channels? How does their passage work? How does movement work? What do they look like?
- Ion channels form a narrow aqueous pore
*Passage is highly selective for a single ion type
*Selection accomplished by a selectivity filter found in the pore
*Aqueous pore can be closed or open: gated
*Movement is from high to low electrochemical gradient never the other way
*Rate of ion flow can be 10^5 times faster than any known transporter
106
What are the functions of the channels?
*Regulate propagation of electrical signals in neurons
*Regulate neuron-to-neuron communication
*Muscle contraction and senses (hearing, touch)
*Epithelial function (intestine, respiratory tract, etc)
*Leaf-closing response
*Even single-cell organisms like reversing direction of
Paramecium
*Membrane potential
107
Explain membrane potential. What does it look like? K+ leaks, leak channels, what happens?
*As K+ leaks, the cell becomes increasingly negative, creating an electrical field
*Leak is allowed by K+ leak channels in the plasma membrane: K+ moves to its chemical gradient by the P-type Na+-K+ Antiporter Pump
*Due to a K+ leak from the cytosol (high [K+]) to the outside (low [K+])
*This electrical field eventually prevents further net movement of K+
despite there still being high [K+] in the cytosol relative to outside of the cell
*The net movement is a balance between electrical and chemical concentration gradients
*The resting membrane potential is the equilibrium condition when there is no net flow of ions
108
What are the two ways cells generate membrane potential?
1) Na+/K+ Pump
(active transport)
2) Passive transport of K+
(K+ “leak”)
109
How does a K+ channel select K+ and
excludes Na+?
* Selectivity filter allows only K+ to pass
* Carbonyl oxygen has partial negative -> displaces interactions of K+ with water, which allows K+ to pass
110
Whats the Selectivity mechanism of a K+? Why K+ over Na+?
*Selectivity of K+ over Na+ is based on complete dehydration of K+
*The 4 carbonyl oxygens in the pore can substitute 4 water molecules
that interact with K+ but not with Na+
111
Ion channels are __________ for
neuronal function: receive,
conduct and transmit signals
The form of this signal is a change
in the ______________
- quintessential
- plasma membrane potential
