BIOC*3560 Part E: Membranes
What is the steroid nucleus?
A characteristic part of the structure of sterols. It consists of four fused rings: three 6C rings + 1 5C ring. The steroid nucleus is almost planar and is relatively rigid; the fused rings do not allow rotation about C-C bonds.
What is the role of helices 1, 2, 3, 4 in the Na+ channel?
*Helices 1, 2, 3, 4* = part of voltage-gating mechanism The four separate chains are fused into a single polypeptide, serving as domains I-IV. Helix 4 specifically is the voltage-sensing helix. I can move in response to changing membrane voltage.
What does SNARE stand for?
*S*oluble *N*-ethylmaleimide-sensitive factor *a*ttachment protein *re*ceptor
State the role of each of the six helices in the Na+ channel.
*helix 1, 2, 3, 4* = part of voltage-gating mechanism helix 4 = voltage-sensing helix *helix 5* = faces the membrane *helix 6* = a pore-forming helix; activation gate
List two functions of the sugar groups on glycoproteins and glycolipids.
- Contribute to cell surface recognition - Function as receptors
Give three examples of β-barrel integral membrane proteins.
- FepA - OmpLA - maltoporin
List three ways membrane are dynamic.
- They can *change shape* without loss of integrity or becoming leaky - Fluid mosaic model (allows *lateral movement* and "Flipping/Flopping/Scrambling") - Membranes usually bounce off each other, but *can fuse*
List the two main sphingolipids
- ceramide - sphingomyelin
What drives Na+-glucose symporters?
- high extracellular [Na+] (chemical potential) - the membrane (electrical) potential, which is inside negative and therefore draws Na+ inward.
How do peripheral membrane proteins stay on cell membranes?
- interaction w/ polar head groups of membrane lipids - electrostatic interactions - hydrogen bonds
List the four main glycerophospholipids
- phosphatidic acid - phosphatidylethanolamine - phosphatidylcholine - phosphatidylserine
Briefly list the six types of transport across a membrane
- simple diffusion - facilitated diffusion - primary active transport - secondary active transport - ion channel - ionophore-mediated ion transport
The membrane potential, ΔΨ, of a typical cell membrane is -60 mV. Is it more negative inside the cell, or outside of the cell?
-ve inside
Briefly list the four steps for "cargo" to be trafficked from a parent membrane to a target membrane.
1) *Budding* (fission) of the vesicle from the parent membrane 2) *Transport* of the vesicle 3) *Tethering*/docking at target membrane (recognition) 4) *Fusion* of vesicle and target membranes
What makes the K+ channel selective for K+?
1) Size 2) Partial negative charges on C=O (Gly-Tyr-Gly-Val-Thr)
List the four steps in the operation of GLUT1.
1) Substrate binds on one side of membrane 2) Conformational change takes place 3) Site opens on other side of membrane & substrate is released 4) Conformational change takes place
List the steps in the Na+K+ATPase transport cycle.
1) Transporter binds 3 Na+ from the inside of the cell 2) Phosphorylation favours P-EnzII [ATP used to phosphorylate the enzyme] 3) Transporter releases 3 Na+ to the outside of the cell, and binds 2 K+ from outside of the cell 4) Dephosphorylation favours EnzI 5) Transporter releases 2 K+ to the inside of the cell
List three things that differ between channels and transporters.
1. Rate of flux 2. Saturability 3. Channels are gated
What are the three membrane transporter classifications?
1. Uniport 2. Symport 3. Anitport (note: symport & antiport are types of cotransport)
How many transmembrane helices does each subunit of the voltage-gated K+ channel have?
2 transmembrane helices (plus one short helix)
What is *spectrin*?
Spectrin is part of the *cytoskeleton*. It links to membrane proteins through *ankyrin*. It may act as the corral, keeping lipids from diffusing freely
What does single particle tracking reveal about the movement of membrane lipids?
That lipids diffuse rapidly and freely *within a restricted region*. More rarely, they *"hop"* into a new region. Lipids behave as though they are corralled by fences, which they occasionally escape
How do Na+-glucose symporters in the small intestine work?
The Na+-glucose symporters take up glucose from the intestine in a process driven by the downhill flow of Na+: *2Na+(out) + glucose(out)➡ 2Na+(in) + glucose(in)* The energy required for this process comes from two sources: - the greater concentration of Na+ outside than inside (the chemical potential); and - the membrane (electrical) potential, which is inside negative and therefore draws Na+ inward.
Why don't hydrophilic solutes cross cells' plasma membranes via simple diffusion?
The activation energy for diffusion through the bilayer is very high
How does a detergent remove an integral membrane protein from a cell membrane?
The detergent coats the hydrophobic domain of the intergral membrane protein -> stops it from interacting w/ other membrane lipids ∴ it comes loose
How do annular lipids interact with receptors?
The head groups of "annular"lipids interact with the *hydrophilic extracellular loops* of receptor proteins (e.g., of aquaporins). The fatty acids tails interact with the *transmembrane helices*.
How do SNAREs mediate vesicle fusion?
They have extended helical domains that can interact to form a coiled-coil structure with SNAP25
What is secondary active transport?
Transport of one ion down its concentration gradient can drive transport of another solute up its gradient
T/F: "Bacterial and mitochondrial outer membrane proteins are β-barrels."
True
T/F: "Bacteriorhodopsin is part of the G-protein coupled receptor family."
True
T/F: "Flippases and floppases require ATP to catalyze transbilayer translocations."
True
T/F: "If a neutral compound is at equilibrium on either side of a membrane, there is not net flux of the solute."
True
T/F: "Ion channels are present in plasma membranes of all cells."
True
T/F: "Lipid bilayers are impermeable to ions and polar molecules."
True
T/F: "Membranes are very dynamic."
True
T/F: "Na+K+ATPase uses up ATP to maintain Na+ and K+ ion gradients."
True
T/F: "Passive transporters are highly specific (stereospecific)."
True
T/F: "Rate of transport through membrane channels is not saturable (no maximum rate of transport)."
True
T/F: "Sphingolipids are similar in shape to glycerolipids."
True
T/F: "Sphingolipids structurally resemble glycerolipids."
True
T/F: "The extracellular loops of bacteriorhodopsin are short."
True
T/F: "The ionic composition of the cytosol is different from the extracellular environment."
True
T/F: "When considering the movement of a charged solute across a membrane, the potential difference across the membrane is 0 at equilibrium."
True
T/F: "Hydrophobic strands that make up β-barrels don't show up on hydrophathy plots."
True, because hydropathy plots detect hydrophobic sections that are > 20 residues long, whereas β-barrel strands can be only 7 residues
T/F: "ATP is generated by reversing F-type ATPases."
True. *In the forward direction:* Protons can be pumped against the concentration gradient at the expense of ATP *In the reverse direction:* ATP can be generated at the expense of protons flowing down their concentration gradient
T/F: "Movement of ions across membranes via ion channels is very rapid."
True. 10^7 to 10^8 ions/s per channel
T/F: "Cells can regulate lipid composition."
True. ^Cells regulate lipid composition to achieve a constant membrane fluidity
T/F: "Solutes flow very rapidly through membrane channels."
True. ^diffusion-like rates of ~10^8 molecules/s
T/F: "For a charged solute, the energy of moving the solute in the chemical and electrical gradients is additive."
True. ΔG = RT ln (c2/c1) + zFΔΨ (can add the chemical potential & the electrical potential)
T/F: "The cell uses ATP to maintain its ion gradients."
True. Ion gradients are actively maintained by the cell, at the cost of ATP.
T/F: "In addition to ion gradients existing across the plasma membrane, there are also ion gradients across organelle membranes."
True. There are ion gradients across the plasma membrane and organelle membranes.
T/F: "Channels with gates are closed by default."
True. They open in response to specific stimulus.
Which amino acid residue(s) on transmembrane proteins are concentrated at the membrane interface (i.e., where the polar head groups meet the acyl chains)?
Tyrosine & Tryptophan
Cholesterol has a polar head group. What is it?
a simple alcohol group: -OH
Which of the following transporters is responsible for importing glucose for erythrocytes? a) GLUT1 b) GLUT2 c) GLUT4 d) Na+-glucose transporter e) none of the above
a) GLUT1
All N-linked carbohydrates are linked through which monosaccharide and which amino acid(s)? a) N-Acetylglucosamine & asparagine b) N-Acetylglucosamine & aspartate c) N- Acetylgalactosamine & asparagine d) N- Acetylgalactosamine & aspartate e) N- Acetylgalactosamine & serine/threonine
a) N-Acetylglucosamine & asparagine ^a.k.a. GlcNAc & Asn
State whether the concentration of each ion is kept at a higher concentration inside the cell, or outside of it. a) Na+ b) Cl- c) K+
a) Na+ - *much higher conc. outside* (150 mM vs. 10 mM) b) Cl- - *much higher conc. outside* (110 mM vs. 5 mM) c) K+ - *much higher conc. intside* (140 mM vs. 5 mM)
Which of the following is NOT a point of difference between channels and transporters? a) Specificity b) Rate of flux c) Saturability d) Whether gated or not e) none of the above
a) Specificity
The net result of the gradients generated by Na+K+ATPase is: a) a net negative charge inside the cell b) a net negative charge outside the cell c) a net charge across the membrane of +90V d) a net charge across the membrane of -90V
a) a net negative charge inside the cell
State the head group substituent of each of the following sphingolipids: a) ceramide b) sphingomyelin
a) ceramide - *just a hydrogen (-H)* b) sphingomyelin - *phosphocholine*
Passive transporters move solutes: a) down their concentration gradient b) along an H+ concentration gradient c) up their concentration gradient d) away from equilibrium
a) down their concentration gradient ^also known as facilitated diffusion
Which of the following enzymes moves phosphatidylethanolamine (PE) and phosphatidylserine (PS) only from the outer leaflet to the cytosolic leaflet? a) flippases b) floppases c) scramblases d) all of the above e) none of the above
a) flippases
In which of the following lipid bilayer states are the lipids ordered in a paracrystalline state? a) gel b) liquid ordered, Lo c) liquid disordered, Ld d) none of the above
a) gel
In which of the following lipid bilayer states is all motion of bilayer is constrained? a) gel b) liquid ordered, Lo c) liquid disordered, Ld d) none of the above
a) gel
What is the backbone in each of the following lipids? a) glycerophospholipids b) sphingolipids
a) glycerophospholipids - *glycerol* b) sphingolipids - *sphingosine*
How many transmembrane segments does each of the following have? a) glycophorin A b) bacteriorhodopsin
a) glycophorin A - *1* b) bacteriorhodopsin - *7*
Where would a Glu residue likely be found on a transmembrane protein? a) in the aqueous phase b) at the membrane interface c) in the hydrophobic region
a) in the aqueous phase ^Charged residues (Arg, Lys, Glu, Asp) are found almost exclusively in the aqueous phase
Where would a Lys residue likely be found on a transmembrane protein? a) in the aqueous phase b) at the membrane interface c) in the hydrophobic region
a) in the aqueous phase ^Charged residues (Arg, Lys, Glu, Asp) are found almost exclusively in the aqueous phase
Where would an Arg residue likely be found on a transmembrane protein? a) in the aqueous phase b) at the membrane interface c) in the hydrophobic region
a) in the aqueous phase ^Charged residues (Arg, Lys, Glu, Asp) are found almost exclusively in the aqueous phase
Where would an Asp residue likely be found on a transmembrane protein? a) in the aqueous phase b) at the membrane interface c) in the hydrophobic region
a) in the aqueous phase ^Charged residues (Arg, Lys, Glu, Asp) are found almost exclusively in the aqueous phase
What percentage of a typical cell membrane is composed of the following: a) lipids b) proteins c) carbohydrates
a) lipids *~45%* b) proteins *~50%* c) carbohydrates *~5%*
In phosphoglycerides (glycerophospholipids) the two fatty acids are connected to the glycerol backbone in a _________________________ linkage. a) amide b) ester c) glycosidic d) ionic e) phosphodiester
b) ester
Which of the following enzymes moves phospholipids only from the cytosolic leaflet to the outer leaflet? a) flippases b) floppases c) scramblases d) all of the above e) none of the above
b) floppases
A lipid is composed of *glycerol + 2 fatty acids + phosphate + an alcohol-derived head group*. Which of the following best describes it? a) triacylglycerol b) glycerophospholipid c) sphingolipid d) galactolipid e) glycosphingolipid
b) glycerophospholipid
If detergent is needed to remove a membrane protein, that means the protein is a(n): a) peripheral protein b) integral protein c) lipid-anchored protein
b) integral protein
Which of the following is the basic matrix of all biological membranes? a) lipid monolayers b) lipid bilayers c) micelles d) liposomes
b) lipid bilayers
Which of the following has a center filled with aqueous solution? a) lipid monolayers b) liposomes c) micelles d) 2 of the above e) none of the above
b) liposomes
Which of the following is the physiological state of the lipid bilayer (cell membranes)? a) gel b) liquid ordered, Lo c) liquid disordered, Ld
b) liquid ordered, Lo
Which of the following lipid bilayer states involves intermediate thermal motion of acyl chains and atoms? a) gel b) liquid ordered, Lo c) liquid disordered, Ld d) none of the above
b) liquid ordered, Lo
Bacteriorhodopsin is a(n): a) single spanning transmembrane protein b) multi-spanning transmembrane protein c) lipid-anchored protein d) peripheral membrane protein
b) multi-spanning transmembrane protein (has 7 transmembrane segments)
Which of the following lipids pack well into liquid-ordered state? a) saturated short chain fatty acids b) saturated long chain fatty acids c) unsaturated fatty acids d) cholesterol
b) saturated long chain fatty acids ^ e.g., C16:0, C18:0
How does cholesterol increase membrane fluidity in membrane w/ a lot of long, saturated fatty acids?
b/c cholesterol interferes with acyl chains--> keeps them from interacting
What keeps the strands of β-barrels together?
backbone hydrogen bonds
What effect does *tetrodotoxin* (produced from puffer fish (fugu)) have on a person?
binds to Na+channels of neurons --> toxic
Sphingolipids consist of ____ fatty acids connected to the backbone in a __________ link. a) 2, amide b) 2, ester c) 1, amide d) 1, ester e) 2, glycosidic
c) 1, amide
Membrane lipids are: a) hydrophilic b) hydrophobic c) amphipathic d) detergents
c) amphipathic
Which of the following lipids is MOST abundant in the plasma membrane? a) sphingolipids b) phosphatidylcholine c) cholesterol d) cardiolipin e) phosphatidylethanolamine
c) cholesterol
If a membrane protein is released when phospholipase is added, that means the protein is a(n): a) peripheral protein b) integral protein c) lipid-anchored protein
c) lipid-anchored protein
In which of the following lipid bilayer states are hydrocarbon chains in constant motion w/ no regular organization? a) gel b) liquid ordered, Lo c) liquid disordered, Ld d) none of the above
c) liquid disordered, Ld
Which lipid bilayer state is favoured by unsaturated & shorter chain fatty acids? a) gel b) liquid ordered, Lo c) liquid disordered, Ld d) none of the above
c) liquid disordered, Ld
Most membrane lipids are ___________ a) cholesterol b) glycolipids c) phospholipids d) sphingolipids e) free fatty acids
c) phospholipids
Which of the following enzymes can move membrane lipids in either direction (outer leaflet ↔ cytosolic leaflet) towards equilibrium? a) flippases b) floppases c) scramblases d) all of the above e) none of the above
c) scramblases
A lipid is composed of *sphingosine + 1 fatty acid + phosphate + choline*. Which of the following best describes it? a) triacylglycerol b) glycerophospholipid c) sphingolipid d) galactolipid e) glycosphingolipid
c) sphingolipid
Na+K+ATPase is a ... a) monomer b) dimer, αβ c) tetramer, α2β2 d) hexamer, α3β3 e) hexamer, β6
c) tetramer, α2β2
Which of the six Na+ channel helices has a high net positive charge, and is sensitive to membrane voltage? a) α-helix 1 b) α-helix 3 c) α-helix 4 d) α-helix 5 e) α-helix 6
c) α-helix 4
in the Na+ channel, which helix faces the membrane? a) α-helix 1 b) α-helix 3 c) α-helix 5 d) α-helix 6 e) none of the above
c) α-helix 5
Bacterial and mitochondrial outer membrane proteins are ____________ a) peripheral membrane proteins b) all enzymes c) β-barrels d) all of the above e) none of the above
c) β-barrels
How does cholesterol decrease membrane fluidity in membrane w/ a lot of unsaturated, cis fatty acids?
cholesterol allows efficient packing of kinked chains
Why does cholesterol increase membrane fluidity at low temperatures?
cholesterol prevents acyl chains from interacting
What "shape" are lipids in a micelle?
cone-shaped
What "shape" are lipids in a lipid bilayer?
cylindrical
Which of the following is NOT a function/result of Na+ and K+ gradients across cell membranes? a) Control cell volume b) Driving of active transport of other species c) Rendering nerve cells electrically excitable d) Control of cell temperature e) none of the above
d) Control of cell temperature
Which of the following transporters is often referred to as a "pump"? a) passive transporter b) ionophore c) ion channel d) active transporter e) none of the above
d) active transporter
Which of the following enzymes catalyzes transbilayer translocations? a) flippases b) floppases c) scramblases d) all of the above e) none of the above
d) all of the above
Which of the following cannot cross a lipid bilayer? a) glycerol b) carbon dioxide c) ethanol d) amino acids e) oxygen
d) amino acids
A lipid is composed of *glycerol + 2 fatty acids + mono-/disaccharide + sulphate*. Which of the following best describes it? a) triacylglycerol b) glycerophospholipid c) sphingolipid d) galactolipid e) glycosphingolipid
d) galactolipid
Which of the following is NOT mediated by intracellular membrane traffic? a) reorganization of membrane-bound compartments b) exchange of membrane and "cargo" between compartments c) internalization/recycling/degradation of material from plasma membrane d) intracellular propagation of action potentials e) none of the above
d) intracellular propagation of action potentials ^within the same cell, an action potential is propagated by flow of ions
Artificial __________ allow the study of membrane transporters. a) lipid monolayers b) micelles c) lipid bilayers d) liposomes e) all off the above
d) liposomes ^vesicles
Which of the following results in a solute being moved against its gradient? a) facilitated diffusion b) ion channel c) passive transport d) primary active transport e) ionophore-mediated ion transport
d) primary active transport
What is rate of solute transport through membrane channels proportional to? a) size of channel b) type of cell c) type of solute d) substrate concentration e) none of the above
d) substrate concentration
The voltage-gated K+ channel is a: a) monomer b) dimer c) trimer d) tetramer e) hexamer
d) tetramer
In the Na+ channel, which helix is the pore-forming helix? a) α-helix 1 b) α-helix 3 c) α-helix 5 d) α-helix 6 e) none of the above
d) α-helix 6
The voltage-gated K+ channel is... a) 10 fold more selective for K+ than Na+ b) 10 fold more selective for Na+ than K+ c) 50 fold more selective for K+ than Na+ d) 50 fold more selective for Na+ than K+ e) 10'000 fold more selective for K+ than Na+
e) 10'000 fold more selective for K+ than Na+
What type of molecules form micelles? a) lipids w/ 1 acyl tail b) lipids w/ 2 acyl tails c) lipids w/ 3 acyl tails d) detergents e) 2 of the above
e) 2 of the above [a) lipids w/ 1 acyl tail & d) detergents] ^the head group needs to be wider than the tail so the layer curves
Which of the following is a passive transporter? a) GLUT1 b) Na+-glucose transporter c) ATPase d) GLUT2 e) 2 of the above
e) 2 of the above ^ a) & d) --> GLUT1 & GLUT4
How much of your total ATP is used by Na+K+ATPase while you're at rest? a) 0% b) 0.1% c) 1% d) 2% e) 25%
e) 25% ^This ATPase uses ¼ of your ATP when at rest
Most O-linked carbohydrate covalent attachments to proteins involve a linkage between which monosaccharide and which amino acid(s)? a) N-Acetylglucosamine & asparagine b) N-Acetylglucosamine & serine/threonine c) N- Acetylgalactosamine & asparagine d) N- Acetylgalactosamine & aspartate e) N- Acetylgalactosamine & serine/threonine
e) N- Acetylgalactosamine & serine/threonine ^a.k.a. GalNAc & Ser/Thr
The head groups of phosphoglycerides (glycerophospholipids) are derived from...? a) amines b) amides c) ketones d) esters e) alcohols
e) alcohols
Which of the following is not a structural feature of cholesterol? a) -OH head group b) 5C ring c) 6C ring d) alkyl side chain e) glycerol backbone
e) glycerol backbone
A lipid is composed of *sphingosine + 1 fatty acid + mono-/oligosaccaride*. Which of the following best describes it? a) triacylglycerol b) glycerophospholipid c) sphingolipid d) galactolipid e) glycosphingolipid
e) glycosphingolipid
Which of the following lipids is part of ABO blood typing? a) cholesterol b) free fatty acids c) glycerophospholipids d) sphingolipids e) glycosphingolipids
e) glycosphingolipids
Which of the following processes do SNAREs NOT play a key role in? a) insulin secretion b) up-regulation of glucose transporters c) transport between ER and Golgi d) phagocytosis e) none of the above
e) none of the above ^SNAREs are key to all of the processes listed, as they are needed to mediate membrane fusion (i.e., of vesicles)
_______________________________ is a major lipids found in all membranes. a) sphingolipids b) phosphatidylcholine c) cholesterol d) cardiolipin e) phosphatidylethanolamine
e) phosphatidylethanolamine
How many helices form the pore of the Na+ channel?
four
Membrane composition is dictated by ___________________?
function
Spingolipids with carbohydrate head groups are called...?
glycosphingolipids
______________________ and ____________________ define the permeability of membranes to ions.
ion channels & ion pumps
Which part of the Na+ channel is the inactivation domain?
it's a small soluble domain that connects domains III and IV
The phosphoglyceride (glycerophospholipid) with choline for a head group substituent is called...?
phosphatidylcholine
The phosphoglyceride (glycerophospholipid) with ethanolamine for a head group substituent is called...?
phosphatidylethanolamine
The phosphoglyceride (glycerophospholipid) with serine for a head group substituent is called...?
phosphatidylserine
In a lipid monolayer, which part of the lipids interact with the water?
polar head groups
In a micelle, which part of the lipids interact with the water?
polar head groups
Why does cholesterol decrease membrane fluidity at high temperatures?
rigid cholesterol interacts with flexible acyl chains
How many types of integral membrane proteins are there?
six (type I, II, III, IV, V, VI)
Which is faster: uncatalyzed transbilayer ("flip-flop") diffusion of membrane lipids, or uncatalyzed lateral diffusion of bilayer lipids?
uncatalyzed lateral diffusion (very fast--> seconds) (Recall that at physiological temperatures, uncatalyzed transbilayer ("flip-flop") diffusion of membrane lipids is very slow (days)).
What are aquaporins?
water channels
In a typical plasma membrane, what percentage is lipids?
~45%
In a typical plasma membrane, what percentage is carbohyrdates?
~5%
In a typical plasma membrane, what percentage is protein?
~50%
Approximately how many amino acids are in the extended helical domains of v-SNAREs and t-SNAREs?
~60 aa
What is the equation for the difference in free energy of charged species on either side of a membrane?
ΔG = zFΔΨ where: z = unit charge F = Faraday constant
Assume an ion moves from a place of high [ion] to a place of low [ion]. Is the free energy of solution, ΔG, positive or negative?
ΔG when molecule moves from c1(high) to c2(low): ΔG = RT ln c2-RT ln c1 = RT ln (c2/c1) If c1> c2, ln (c2/c1) is -ve, so ΔG is -ve
What is the equation for free energy of solution?
ΔG= ΔGo+ RT ln(c) where R= constant T= temp. in Kelvin c = concentration
Na+K+ATPase is a tetramer with 2α subunits and 2β subunits. Which subunit performs ion transport?
α
Which part of the Na+ channel is the activation gate?
α-helix 6
List the two types of stimulus that can be used to open different types of gated ion channels.
◾ ligand-gated ◾ voltage-gated
What is *ankyrin*?
Ankyrin is a type of adaptor protein that mediates the attachment of integral membrane proteins to the *spectrin*-actin based membrane cytoskeleton
What are annular lipids?
Annular lipids represent a select set of lipids which preferentially bind or stick to the surface of membrane proteins in biological cells. The word "annular" in general means"ring-shaped".
List two examples of aquaporin variants
Aquaporin variants also transport *glycerol* or *urea*
Why does transbilayer motion or "flip-flop"of membrane lipids occur very slowly at physiological temperatures?
Because it requires that the polar or charged head group leave its aqueous environment and move through the hydrophobic interior of bilayer
Why does the cell spend energy maintaining ion gradients?
Because the gradients can be used to do work
Why do bacteria synthesize more unsaturated fatty acids and fewer saturated ones when cultured at low temperatures?
Because unsaturated fatty acids favour greater membrane fluidity, which combats the decreased membrane fluidity from the cold (cold => gel state)
What role do the carbonyl (C=O) oxygens play in the K+ channel's specificity for K+ over Na+?
Carbonyl oxygens of the peptide backbone in the selectivity filter, protrude into the channel, interacting with and stabilizing a K+ ion passing through. These ligands are perfectly positioned to interact with each of four K+ ions, but not with the smaller Na+ ions. This preferential interaction with K is the basis for the ion selectivity. --> carbonyl oxygen coordinate with un-hydrated K+
What is the major animal cell sterol?
Cholesterol
Describe the role of t-SNAREs, v-SNAREs, and SNAP25 in vesicle fusion.
During fusion, a *v-SNARE and t-SNARE bind to each other* and undergo a structural change that produces a bundle of long, thin rods made up of helices from both SNARES and two helices from SNAP25. The two SNAREs initially interact at their ends, then *zip up* into the bundle of helices. This structural change *pulls the two membranes into contact* and initiates the fusion of their lipid bilayers.
T/F: "For a neutral (uncharged) solute, the energy of moving the solute in the chemical and electrical gradients is additive."
False
T/F: "GLUT1 transports glucose against its concentration gradient, and requires ATP."
False, GLUT1 is a passive transporter ∴ transports glucose from high -> low concentration (i.e., WITH the gradient)
T/F: "All cells in an organism have highly similar membrane compositions; however, there is variation between individuals."
False, different membrane types have different membrane compositions, within the same individual.
T/F: "The rate of transport of by passive transporters is free/ unregulated."
False, it IS regulated.
T/F: "'Minor lipids' are called minor lipids because of their relative unimportance."
False, it is because they are found in smaller quantities in cell membranes
T/F: "Unless they are part of a cell, lipid bilayers are permeable to ions/ polar molecules."
False, lipid bilayers are impermeable to ions and polar molecules
T/F: "A cell's plasma membrane is symmetrical."
False, proteins are "sided"-- outside is different from inside
T/F: "Sphingolipids and glycerolipids shapes are distinct from one another."
False, sphingolipids are similar in shape to glycerolipids
T/F: "Channels with gates are open by default."
False, they are closed by default and let nothing past. They open in response to specific stimulus.
T/F: "Membranes are largely static/ unchanging."
False, they are dynamic
T/F: "The extracellular loops of bacteriorhodopsin are long and twisted."
False, they are short
T/F: "Rate of transport through passive transporters is not saturable (no maximum rate of transport)."
False, they have a saturable number of binding sites for substrate.
T/F: "Most membrane channels transport a wide variety of substances, i.e., are non-specific."
False, they're all highly selective in what they let through
T/F: "Lipids are randomly distributed in a membrane."
False. Lipids are not randomly distributed, even within a leaflet (e.g., microdomains, lipid rafts, aggregates).
T/F: "Passive transporters are a continuous pore through the cell membrane."
False. Passive transporters are not a continuous pore through the membrane
T/F: "Passive transporters can transports multiple sets of molecules at a time."
False. Passive transporters transport one set of molecule(s) at a time.
T/F: "Sphingolipids do not share structural similarities with glycerolipids."
False. Sphingolipids structurally resemble glycerolipids.
T/F: "The ionic composition of the cytosol is essentially the same as that of the extracellular environment."
False. The ionic composition of the cytosol is *different* from the extracellular environment.
T/F: "Transporters and ion channels are essentially the same thing."
False. Transporters and ion channels are fundamentally different
T/F: "Solutes flow very rapidly through transporters."
False. they flow rapidly through *channels*.
What causes a lipid bilayer to change from the lipid ordered state (Lo) to the lipid disordered state (Ld)?
Heat --> increased heat produces thermal motion of side chains , which leads to the Lo -> Ld transition
How does the voltage-gated Na+ channel open? (What stimulates it + what internal changes cause it to respond)
Helix 4 has a high net positive charge, and is sensitive to membrane voltage. The net negative charge inside the cell pulls +ve helix 4 inward. When the membrane is depolarized helix 4 is not pulled inward as much (it relaxes), and moves towards outside. Coupled movements in helix 6 (lining the pore) opens the channel. After opening, channel is quickly blocked by the inactivation loop, stopping ions from passing
What is a hydropathy plot? What is it used for?
Hydropathy plots allow for the visualization of hydrophobicity over the length of a peptide sequence. A hydropathy scale which is based on the hydrophobic and hydrophilic properties of the 20 amino acids is used.
By looking at a hydropathy plot, how can you tell where a likely transmembrane domain is on a protein?
If > 20 successive residues have a high hydropathy index, possibly a transmembrane segment
How does α-helix 4 function as a voltage sensor in the Na+ channel?
It has a high net positive charge, so the net negative charge inside the cell pulls it inward. When the membrane is depolarized helix 4 is not pulled inward as much (it relaxes), and moves towards outside. Coupled movements in helix 6 (lining the pore) opens the channel. After opening, channel is quickly blocked by the inactivation loop, stopping ions from passing
What is a lipid raft?
Lipid rafts are *subdomains of the plasma membrane* that contain high concentrations of cholesterol and glycosphingolipids. They exist as distinct liquid-ordered regions of the membrane that are resistant to extraction with nonionic detergents.
Why do a lot of toxins target Na+ channels?
Many toxins target ion channels as the effects are fast acting and very debilitating
What does it mean for a channel to be "gated"?
Means it is not always open, but opens/closes in response to stimuli
The pore is smaller in which channel: Na+ channel or K+ channel?
Na+ channel has smaller pore
What effect do diseases of Na+ channels have on muscles?
Na+-channel defects result in diseases where muscles are paralyzed or stiff
Which protein is responsible for generating gradients of Na+and K+?
Na+K+ATPase
How do Na+ channels differ from K+ channels?
Na+channels differ from K+channels predominantly in having a narrower specificity pore (as Na+ is smaller)
How would a pH change or a chelator cause a peripheral membrane protein to come off a cell membrane?
Peripheral membrane proteins have stabilizing Ca2+ interactions which are disrupted by changes in pH or chelators.
In each of the following cases, would cholesterol increase or decrease membrane fluidity? a) membrane w/ lots of long, saturated fatty acids b) membrane w/ lots of unsaturated, cis fatty acids c) membrane @ high temperature d) membrane @ low temperature
a) membrane w/ lots of long, saturated fatty acids - *increases fluidity* b) membrane w/ lots of unsaturated, cis fatty acids - *decreases fluidity* c) membrane @ high temperature - *decreases fluidity* d) membrane @ low temperature - *increases fluidity*
In terms of lipid-anchored proteins, state where on a protein each of the following lipid anchors would attach: a) palmitoyl group b) N-myristoyl group c) farnesyl (or gerarylgeraryl) group d) GPI anchor
a) palmitoyl group - *on internal Cys (or Ser)* b) N-myristoyl group - *on N-terminal Gly* c) farnesyl (or gerarylgeraryl) group - *on C-terminal Cys* d) GPI anchor - *on carboxyl terminus*
If a pH change or chelator (removes stabilizing Ca2+) releases a membrane protein, that means the protein is a(n): a) peripheral protein b) integral protein c) lipid-anchored
a) peripheral protein
State how you would remove each of the following proteins from a cell membrane: a) peripheral protein b) integral protein c) lipid-anchored protein
a) peripheral protein - *pH change or chelator* b) integral protein - *detergent* c) lipid-anchored protein - *phospholipase*
State the net charge of each of the following phosphoglycerides (glycerophospholipids) at ph 7: a) phosphatidic acid b) phosphatidylethanolamine c) phosphatidylcholine d) phosphatidylserine
a) phosphatidic acid *-2* b) phosphatidylethanolamine *0* c) phosphatidylcholine *0* d) phosphatidylserine *-1*
State the head group substituent of each of the following glycerophospholipids: a) phosphatidic acid b) phosphatidylethanolamine c) phosphatidylcholine d) phosphatidylserine
a) phosphatidic acid - *just a hydrogen (-H)* b) phosphatidylethanolamine - *ethanolamine* c) phosphatidylcholine - *choline* d) phosphatidylserine- *serine*
Briefly describe how each of the following types of membrane transport works: a) simple diffusion b) facilitated diffusion c) primary active transport d) secondary active transport e) ion channel f) ionophore-mediated ion transport
a) simple diffusion - *done by non-polar compounds only--> travel down gradient* b) facilitated diffusion - *occurs down electrochemical gradient* c) primary active transport -*occurs against electrochemical gradient & requires ATP* d) secondary active transport - *goes against electrochemical gradient; driven by ion moving down its gradient* e) ion channel - *down electrochemical gradient; may ligand-gated/ ion-gated* f) ionophore-mediated ion transport - *down electrochemical gradient*
Glycophorin A is a(n): a) single-spanning transmembrane protein b) multi-spanning transmembrane protein c) lipid-anchored protein d) peripheral membrane protein
a) single-spanning transmembrane protein
v-SNAREs and t-SNAREs are ... a) single-spanning transmembrane proteins b) multi-spanning transmembrane proteins c) lipid-anchored proteins d) peripheral membrane proteins
a) single-spanning transmembrane proteins
A lipid is composed of *glycerol + 3 fatty acids*. Which of the following best describes it? a) triacylglycerol b) glycerophospholipid c) sphingolipid d) galactolipid e) glycosphingolipid
a) triacylglycerol
Which of the following is NOT found in cell membranes? a) triacylglycerols b) glycerophospholipids c) sphingolipids d) galactolipids e) sulfolipids
a) triacylglycerols ^storage lipid
GLUT1 transports glucose into erythrocytes in a way classified as: a) uniport b) symport c) antiport d) none of the above
a) uniport
Where would a lipid monolayer form?
at the air-water interface: the polar head groups interact with the aqueous solution, and the hydrophobic tails interact with the air
A typical plasma membrane has a membrane potential, ΔΨ, is... a) -110 mV b) -60 mV c) -10 mV d) +10 mV e) +60 mV
b) -60 mV
Glycerophospholipids consist of ____ fatty acids connected to the backbone in a __________ link. a) 2, amide b) 2, ester c) 1, amide d) 1, ester e) 2, glycosidic
b) 2, ester
Na+K+ATPase generates gradients of Na+and K+. How many of each does it move, and in which direction? a) 2 Na+ in, 2 K+ out b) 3 Na+ out, 2 K+ in c) 2 Na+ out, 3 K+ in d) 3 Na+ in, 2 K+ out e) 2 Na+ in, 3 K+ out
b) 3 Na+ out, 2 K+ in
Which of the following transporters imports glucose for the liver & the small intestine? a) GLUT1 b) GLUT2 c) GLUT4 d) Na+-glucose transporter e) none of the above
b) GLUT2
Which of the following transporters imports glucose for the liver? a) GLUT1 b) GLUT2 c) GLUT4 d) Na+-glucose transporter e) none of the above
b) GLUT2
Which of the following transporters imports glucose for the small intestine? a) GLUT1 b) GLUT2 c) GLUT4 d) Na+-glucose transporter e) none of the above
b) GLUT2
Which of the following ions is kept at a higher concentration inside the cell, compared to outside? a) Cl- b) K+ c) Na+ d) all of the above
b) K+
Which of the following transporters generates/ maintains an ion gradient across a membrane? a) passive transporters b) active transporters c) ionophores d) ion channels e) none of the above
b) active transporter
Where would a Trp residue likely be found on a transmembrane protein? a) in the aqueous phase b) at the membrane interface c) in the hydrophobic region
b) at the membrane interface ^Tyrosine and tryptophan residues are concentrated where the polar head groups meet the acyl chains
Where would a Tyr residue likely be found on a transmembrane protein? a) in the aqueous phase b) at the membrane interface c) in the hydrophobic region
b) at the membrane interface ^Tyrosine and tryptophan residues are concentrated where the polar head groups meet the acyl chains
