Biochem 2 Exam 4 Study Guide

Question: Study Guide Question: How does increasing temperature affect membrane lipid organization? Answer: Increasing temperature increases lipid motion and disrupts acyl-chain packing, favoring a more fluid, liquid-disordered membrane.

Question: Why does increasing temperature increase membrane fluidity? Answer: Higher temperature increases thermal motion, allowing more rotation around acyl-chain single bonds and greater lateral movement of lipids. Ordered packing becomes less favorable.

Question: What happens to a lipid bilayer as it passes through its melting temperature? Answer: Ordered, tightly packed acyl chains → increased thermal motion → disrupted packing → a more fluid, liquid-disordered bilayer. The bilayer remains intact while its molecular organization changes.

Question: What is the main structural change tested when a membrane is heated through its phase transition? Answer: Disruption of lipid packing and increased molecular motion. The relevant change is in noncovalent organization; phospholipid covalent bonds remain intact.

Question: Study Guide Question: What are the structural and functional characteristics of membrane proteins? Answer: Membrane proteins associate with the bilayer through embedded hydrophobic regions, surface interactions, or lipid anchors and function in transport, signaling, adhesion, and catalysis.

Question: How do integral, peripheral, and amphitropic membrane proteins differ? Answer: Integral proteins are firmly embedded in the membrane; peripheral proteins associate through noncovalent surface interactions; amphitropic proteins reversibly associate with membranes and also occur in the cytosol.

Question: How does a transmembrane protein accommodate both the membrane interior and aqueous surroundings? Answer: Hydrophobic side chains face the lipid core → polar regions face water or line an internal transport pathway. Transmembrane α-helices internally hydrogen-bond their backbones; β-barrels also satisfy backbone hydrogen bonding within their folded structures.

Question: What is the main defining feature of an integral membrane protein? Answer: Firm insertion into the lipid bilayer through hydrophobic interactions. Many integral proteins span the membrane, but monotopic proteins insert into just one leaflet.

Question: Study Guide Question: What type of transport is involved in glucose uptake by erythrocytes? Answer: GLUT1-mediated facilitated diffusion, a passive glucose uniport process.

Question: Why is glucose uptake through GLUT1 classified as facilitated diffusion? Answer: GLUT1 provides a specific protein-mediated route for glucose to move down its concentration gradient without directly consuming ATP. Glucose is too polar to cross the lipid core rapidly on its own.

Question: How does GLUT1 transport glucose across the erythrocyte membrane? Answer: Outward-facing GLUT1 binds extracellular D-glucose → an occluded intermediate forms → GLUT1 becomes inward-facing → glucose is released into the cytosol → the empty transporter returns outward. The cycle is reversible and does not chemically modify glucose.

Question: What is the most likely exam distinction between erythrocyte GLUT1, GLUT4, and SGLT? Answer: GLUT1 provides basal, insulin-independent facilitated diffusion. GLUT4 undergoes insulin-regulated membrane recruitment; SGLT couples glucose uptake to downhill Na⁺ movement.

Question: Study Guide Question: How do membrane compositions differ between inner and outer mitochondrial membranes? Answer: The inner membrane is more protein-rich and enriched in cardiolipin; the outer membrane contains porins and relatively more lipid. Both contain little sterol.

Question: Why does the inner mitochondrial membrane have a high protein content? Answer: It contains respiratory-chain complexes, ATP synthase, and numerous selective transporters. Its composition supports energy conversion and maintenance of an electrochemical proton gradient.

Question: How do mitochondrial membrane compositions support different permeability properties? Answer: Outer-membrane porins permit passage of many small solutes → the intermembrane space exchanges readily with the cytosol. Inner-membrane lipids and selective transport proteins restrict passage → proton and metabolite gradients can be maintained.

Question: Which mitochondrial membrane contains the respiratory chain and most mitochondrial cardiolipin? Answer: The inner mitochondrial membrane. Cardiolipin is strongly enriched there and supports respiratory-complex organization; it is not a major outer-membrane lipid.

Question: Study Guide Question: How can integral membrane proteins be extracted from membranes? Answer: By disrupting hydrophobic interactions with detergents; organic solvents can also extract them but often denature the proteins.

Question: Why are detergents needed to solubilize integral membrane proteins? Answer: Integral proteins expose hydrophobic surfaces to membrane lipids. Detergents surround these surfaces with their hydrophobic portions while presenting hydrophilic groups to water.

Question: What is the mechanism of detergent extraction of an integral membrane protein? Answer: Detergent partitions into the bilayer → lipid–protein interactions are disrupted → mixed lipid–detergent aggregates form → detergent coats the protein’s hydrophobic surfaces → the protein becomes dispersed in aqueous solution. Mild nonionic detergents are often used to preserve function.

Question: What is the main extraction-method distinction between integral and peripheral membrane proteins? Answer: Integral proteins generally require detergents; peripheral proteins can often be released with high salt or altered pH. The distinction reflects hydrophobic insertion versus surface noncovalent interactions.

Question: Study Guide Question: What determines the potassium channel's selectivity for K⁺ over Na⁺? Answer: Selectivity-filter carbonyl oxygens coordinate dehydrated K⁺ optimally, compensating for its dehydration; smaller Na⁺ is not stabilized equivalently.

Question: Why can a potassium channel exclude Na⁺ even though Na⁺ is smaller than K⁺? Answer: The main factor is favorable coordination of dehydrated K⁺ by the selectivity filter. Na⁺ is too small to interact optimally with the filter’s oxygen ligands, so its dehydration is not adequately compensated.

Question: How does the potassium-channel selectivity filter distinguish K⁺ from Na⁺? Answer: Hydrated ion enters the aqueous vestibule → ion loses its hydration shell at the narrow filter → backbone carbonyl oxygens replace water ligands. K⁺ receives favorable coordination that offsets dehydration; Na⁺ receives insufficient stabilization and faces a larger energetic barrier.

Question: Which chemical groups are the main determinants of K⁺ coordination in the potassium-channel selectivity filter? Answer: Peptide-backbone carbonyl oxygens. Their arrangement mimics the hydration environment of K⁺; other pore features support conduction, but this coordination is the main selectivity concept.

Question: Study Guide Question: How do bacteria adapt their membrane composition to colder temperatures? Answer: They increase unsaturated fatty acids and may increase shorter or branched chains, preventing tight packing and maintaining fluidity.

Question: What is homeoviscous adaptation? Answer: Adjustment of membrane lipid composition to maintain a suitable membrane viscosity as environmental conditions change. Cooling commonly favors lipids with lower melting temperatures.

Question: How does increased fatty acid unsaturation help a bacterium tolerate cooling? Answer: Temperature falls → acyl-chain motion decreases → the cell increases cis-unsaturated membrane fatty acids → double-bond kinks disrupt close packing → the membrane remains functional at the lower temperature.

Question: What is the most likely exam answer for how bacteria preserve membrane fluidity in the cold? Answer: Increase cis-unsaturated fatty acids. Shorter or branched chains can also help, whereas longer saturated chains generally promote rigidity.

Question: Study Guide Question: What is the transport kinetics of GLUT1 in erythrocytes? Answer: GLUT1 exhibits saturable, Michaelis–Menten-like kinetics: v₀ = Vmax[glucose]out/(Kt + [glucose]out).

Question: What do Vmax and Kt mean for GLUT1-mediated glucose uptake? Answer: Vmax is the maximum initial transport rate; Kt is the external glucose concentration producing half-maximal initial transport. Kt is analogous to an enzyme’s Km.

Question: Why does GLUT1-mediated transport approach a maximum rate? Answer: Increasing extracellular glucose increases transporter occupancy → more transport cycles occur → available binding sites and conformational cycling become limiting → uptake approaches Vmax. The initial-rate equation assumes intracellular glucose is initially negligible.

Question: What distinguishes GLUT1 uptake kinetics from simple diffusion through a lipid bilayer? Answer: GLUT1 transport is saturable and stereospecific. Simple diffusion does not show a transporter-limited Vmax and increases approximately with the concentration difference under otherwise fixed conditions.

Question: Study Guide Question: What type of transport systems moves Ca²⁺ into the endoplasmic reticulum against its gradient? Answer: Primary active transport by the P-type Ca²⁺ ATPase SERCA, powered directly by ATP hydrolysis.

Question: Why is SERCA a primary active transporter and a P-type ATPase? Answer: It directly couples ATP hydrolysis to uphill Ca²⁺ transport and forms a transient phosphorylated Asp residue during its catalytic cycle.

Question: What is the ATP-driven transport cycle of SERCA? Answer: E1 binds 2 cytosolic Ca²⁺ → MgATP binds → ATP transfers its terminal phosphate to Asp-351, producing ADP and an occluded phosphoenzyme → conversion to E2-P lowers Ca²⁺ affinity and exposes the sites to the ER lumen → 2 Ca²⁺ are released → hydrolysis of the Asp-phosphate releases Pi → E1 is regenerated. One ATP is consumed per two Ca²⁺ transported; H⁺ countertransport accompanies the cycle.

Question: What transport direction is the main exam association for SERCA? Answer: Cytosol → ER or sarcoplasmic-reticulum lumen. SERCA lowers cytosolic Ca²⁺ and replenishes intracellular Ca²⁺ stores.

Question: Study Guide Question: Which choline-containing lipids are found in the outer leaflet of plasma membranes? Answer: Phosphatidylcholine and sphingomyelin.

Question: How do phosphatidylcholine and sphingomyelin differ structurally despite both containing choline? Answer: Phosphatidylcholine is a glycerophospholipid with a glycerol backbone; sphingomyelin is a sphingolipid with a ceramide backbone. Both have phosphocholine head groups.

Question: How do lipid translocators help maintain plasma-membrane leaflet asymmetry? Answer: Selective ATP-dependent flippases move aminophospholipids inward → floppases move selected lipids outward → slow spontaneous phospholipid flip-flop preserves unequal leaflet compositions. Scramblase activation can dissipate this asymmetry.

Question: Which phospholipids are generally enriched in the cytosolic leaflet rather than the outer leaflet? Answer: Phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol and its phosphorylated derivatives. Phosphatidylcholine and sphingomyelin are generally enriched outside.

Question: Study Guide Question: Which membrane transport processes do not require protein facilitators? Answer: Simple diffusion through the lipid bilayer, including diffusion of small nonpolar molecules and some water.

Question: Why can O₂ and CO₂ cross membranes without transport proteins? Answer: They are small, uncharged molecules that can dissolve in the hydrophobic membrane interior. Their movement down a concentration gradient does not require a protein pathway.

Question: How does a molecule cross a membrane by simple diffusion? Answer: Molecule leaves the aqueous phase → partitions into the lipid bilayer → diffuses through its hydrophobic interior → emerges into the opposite aqueous phase. Net movement follows the concentration gradient and requires no ATP or transporter.

Question: What is the main exam association for rapid water transport across cell membranes? Answer: Aquaporins provide rapid, selective water transport. Water can also diffuse directly through the lipid bilayer, so osmosis itself does not require an aquaporin.

Question: Study Guide Question: Are flippases and floppases considered facilitated transport systems? Answer: They facilitate lipid translocation broadly, but are ATP-dependent active transporters, not passive facilitated-diffusion systems.

Question: Why is “protein-mediated transport” not equivalent to “facilitated diffusion”? Answer: Protein-mediated transport includes both passive and active processes. Facilitated diffusion specifically moves a substance downhill without direct energy input; flippases and floppases consume ATP.

Question: How do flippases, floppases, and scramblases differ mechanistically? Answer: Flippases: selected phospholipids, especially PS and PE, move toward the cytosolic leaflet using ATP. Floppases: selected lipids move toward the outer leaflet using ATP. Scramblases: lipids move bidirectionally down their leaflet concentration gradients without ATP, reducing asymmetry.

Question: Which lipid-translocating proteins are most directly associated with passive loss of leaflet asymmetry? Answer: Scramblases. Some are activated by Ca²⁺, whereas apoptotic scramblases can be activated through caspase-dependent mechanisms.

Question: Study Guide Question: What are the common components of biological membranes? Answer: Lipids and proteins, with carbohydrates attached to lipids or proteins in many membranes.

Question: What are the main structural roles of membrane lipids, proteins, and carbohydrates? Answer: Lipids form the permeability barrier; proteins provide transport, signaling, adhesion, and catalytic functions; carbohydrates contribute recognition and surface protection.

Question: How do amphipathic membrane lipids assemble into a bilayer? Answer: Lipids enter water → hydrophobic tails aggregate to reduce exposure to water → polar head groups remain exposed → two leaflets assemble tail-to-tail → exposed edges close, often producing a sealed vesicle. Assembly is driven largely by the hydrophobic effect.

Question: What is the main form and location of carbohydrates in the plasma membrane? Answer: Oligosaccharides attached to proteins and lipids on the extracellular surface. These form glycoproteins and glycolipids rather than a free carbohydrate layer within the hydrophobic core.

Question: Study Guide Question: What are the general features of lipid bilayers in biological membranes? Answer: They are thin, fluid, asymmetric, self-sealing barriers with hydrophilic surfaces and a hydrophobic interior that selectively restricts solute passage.

Question: Why is a lipid bilayer selectively permeable? Answer: Its hydrophobic interior favors passage of small nonpolar molecules but creates a large energetic barrier for ions and most polar solutes. Transport proteins provide selective routes for otherwise poorly permeant substances.

Question: Why does a damaged lipid bilayer tend to reseal small openings? Answer: An opening exposes hydrophobic acyl chains to water → this exposure is energetically unfavorable → nearby lipids rearrange to bury the tails → the opening closes. Extensive damage can exceed this self-sealing capacity.

Question: Which lipid movements occur readily within a bilayer, and which are usually slow? Answer: Lateral diffusion, rotation, and acyl-chain flexing occur readily. Spontaneous phospholipid movement between leaflets is usually slow because the polar head group must cross the hydrophobic core.

Question: Study Guide Question: What are the key features of the fluid mosaic model of membranes? Answer: A fluid lipid bilayer contains a mosaic of associated proteins, with lateral mobility, structural asymmetry, and locally specialized domains.

Question: What do “fluid” and “mosaic” mean in the fluid mosaic model? Answer: Fluid refers to molecular motion within the bilayer; mosaic refers to the varied proteins and lipids distributed within it. The membrane is a dynamic, heterogeneous structure.

Question: How does lateral diffusion occur without destroying the membrane barrier? Answer: Lipids and mobile proteins exchange positions within the membrane plane → hydrophobic regions remain buried and polar regions remain exposed → the bilayer retains continuity while its components redistribute.

Question: What is the main mobility concept tested by the fluid mosaic model? Answer: Many lipids and proteins can diffuse laterally within the bilayer. Cytoskeletal attachments, protein complexes, and membrane domains can restrict particular proteins’ movement.

Question: Study Guide Question: What are integrins and what is their role in membranes? Answer: Integrins are α/β heterodimeric transmembrane adhesion receptors that connect cells to extracellular ligands and transmit signals across the membrane.

Question: What structural organization allows integrins to link extracellular and intracellular environments? Answer: Each integrin contains an α subunit and a β subunit, each with a single transmembrane helix. Their extracellular domains bind ligands, while cytoplasmic regions associate with intracellular signaling and cytoskeletal proteins.

Question: How do integrins mediate bidirectional signaling? Answer: Inside-out signaling: intracellular regulators alter integrin conformation and ligand affinity. Outside-in signaling: extracellular ligand binding and integrin clustering recruit intracellular proteins → cytoskeletal and signaling responses. Divalent cations support ligand binding.

Question: What integrin-binding sequence is a likely exam target? Answer: RGD, or Arg–Gly–Asp, a recognition motif in several extracellular-matrix ligands, including fibronectin. Some integrins recognize other motifs, but RGD is the key sequence to associate with integrin binding.

Question: Study Guide Question: How do ligand-gated ion channels function in membranes? Answer: Ligand binding changes channel conformation and opens or closes an ion-selective pore, allowing passive ion movement down an electrochemical gradient.

Question: What mainly determines ion direction after a ligand-gated channel opens? Answer: The ion’s electrochemical gradient. Ligand binding controls gating; concentration differences and membrane voltage determine whether net movement is inward or outward.

Question: What is the mechanism of a ligand-gated ion channel? Answer: Ligand binds a regulatory site → channel conformation changes → the gate opens or closes → permitted ions move through the pore according to their electrochemical gradients → ligand dissociation or desensitization terminates the response. Ion passage itself does not require ATP hydrolysis.

Question: How do ligand-gated channels differ from voltage-gated channels? Answer: Ligand-gated channels respond directly to ligand binding; voltage-gated channels respond to membrane potential changes. Both can conduct ions passively when open.

Question: Study Guide Question: What does a hydropathy plot reveal about membrane proteins? Answer: It identifies hydrophobic sequence regions that may form membrane-spanning segments and helps predict membrane topology.

Question: Why does a long hydrophobic sequence suggest a transmembrane α-helix? Answer: A stretch of roughly 20 predominantly hydrophobic residues can form an α-helix long enough to cross the bilayer’s nonpolar core. Its side chains can interact favorably with lipid tails.

Question: How is a hydropathy plot constructed and interpreted? Answer: Assign a hydropathy value to each residue → average values over a sliding sequence window → plot average hydropathy against residue position → identify extended hydrophobic regions → evaluate them as candidate membrane-spanning segments. The direction of “hydrophobic” on the vertical axis depends on the scale used.

Question: What is the main exam interpretation of a long hydrophobic region on a hydropathy plot? Answer: A likely membrane-spanning α-helix, especially when the region is about 20 residues long. Signal peptides and buried hydrophobic regions can produce similar signals, so the plot is predictive rather than definitive.

Question: Study Guide Question: Which molecules are typically enriched in lipid rafts? Answer: Cholesterol, sphingolipids, and selected proteins, especially GPI-anchored and some acylated signaling proteins.

Question: Why do sphingolipids and cholesterol favor raft formation? Answer: Long, relatively saturated sphingolipid chains pack tightly with cholesterol, creating more ordered and often thicker membrane regions than neighboring unsaturated phospholipid-rich regions.

Question: How can lipid rafts organize membrane signaling? Answer: Preferential lipid interactions generate local ordered domains → selected anchored proteins and receptors partition into these regions → signaling components become concentrated or segregated → the likelihood of specific molecular interactions changes. Rafts are dynamic rather than permanent rigid platforms.

Question: Which lipid pair is the most likely exam answer for lipid-raft enrichment? Answer: Cholesterol and sphingolipids. Selected proteins, especially GPI-anchored proteins, also concentrate in rafts, but this lipid pair is the central compositional association.

Question: Study Guide Question: What is the mechanism of facilitated diffusion across membranes? Answer: A specific carrier or channel lowers the barrier to solute passage, allowing movement down its concentration or electrochemical gradient without direct energy input.

Question: How does facilitated diffusion differ from active transport? Answer: Facilitated diffusion is downhill and cannot independently accumulate a solute against its gradient. Active transport couples uphill movement to ATP hydrolysis or another energy source.

Question: How does carrier-mediated facilitated diffusion work? Answer: Solute binds one side of a carrier → the carrier undergoes an alternating-access conformational change → solute is released on the opposite side → the carrier resets. Net movement is downhill; the carrier does not remain simultaneously open to both sides.

Question: What mechanism is most likely tested for GLUT-mediated facilitated diffusion? Answer: Alternating access: substrate binding → carrier conformational change → substrate release on the opposite side. Channels also mediate passive transport, but GLUT proteins are carriers.

Question: Study Guide Question: What enzyme class does the F-type ATPase belong to? Answer: An ATP-driven proton translocase, functioning as a rotary ATPase or, in reverse, an ATP synthase; older classifications group it among ATP-hydrolyzing hydrolases.

Question: Why can F-type ATPase be described as both an ATPase and an ATP synthase? Answer: Its energy coupling is reversible. ATP hydrolysis can drive uphill proton transport, while downhill proton flow can drive ATP synthesis.

Question: How does the F₀F₁ complex couple proton movement to ATP metabolism? Answer: ATP-synthesis direction: H⁺ flows downhill through membrane-embedded F₀ → rotor and central stalk rotate → conformations of F₁ catalytic sites change → ADP and Pi form ATP, which is released. Reverse direction: MgATP hydrolysis in F₁ drives rotation that pumps H⁺ uphill through F₀.

Question: What is the main mechanistic distinction between F-type and P-type ATPases? Answer: F-type ATPases use rotary energy coupling; P-type ATPases form a transient phosphorylated Asp intermediate. Associate F-type with F₀F₁ and reversible ATP synthesis/proton pumping.

Question: Study Guide Question: What proteins mediate fusion of vesicular membrane during neurotransmitter release? Answer: SNARE proteins, particularly vesicular synaptobrevin and plasma-membrane syntaxin and SNAP-25.

Question: What are the respective roles of synaptobrevin, syntaxin, and SNAP-25? Answer: Synaptobrevin is the vesicular SNARE; syntaxin and SNAP-25 are target-membrane SNARE components. Together they assemble a four-helix bundle that promotes fusion.

Question: What is the mechanism of Ca²⁺-triggered synaptic vesicle fusion? Answer: Vesicle docking and priming → partial assembly of synaptobrevin, syntaxin, and SNAP-25 → action potential opens voltage-gated Ca²⁺ channels → Ca²⁺ binds synaptotagmin → final SNARE-driven membrane apposition and fusion-pore opening → neurotransmitter release. After fusion, α-SNAP and the ATPase NSF help disassemble SNARE complexes for reuse.

Question: Which proteins provide the four helices of the neuronal SNARE bundle? Answer: Synaptobrevin contributes one helix, syntaxin contributes one, and SNAP-25 contributes two. SNAP-25 is distinct from α-SNAP, which participates in SNARE recycling.

Question: Study Guide Question: What types of molecules are transported by ABC transporters? Answer: A broad range, including lipids, sterols, bile salts, drugs, peptides, amino acids, proteins, and certain ions.

Question: What does ABC stand for, and what is the basic architecture of an ABC transporter? Answer: ATP-binding cassette. A typical functional transporter has two transmembrane domains and two cytosolic nucleotide-binding domains, which may occur in one or multiple polypeptides.

Question: How does a typical ABC transporter couple ATP to substrate movement? Answer: Substrate binds the transporter → ATP binds the nucleotide-binding domains and promotes their association → transmembrane domains rearrange to expose substrate to the opposite side → substrate is released → ATP hydrolysis and product release reset the transporter. ATPase activity generally requires Mg²⁺.

Question: What is the main exam association for ABC transporters, and what important exception should be recognized? Answer: Most are ATP-driven transporters that move substrates across membranes. The major exception is CFTR, an ATP-regulated Cl⁻ channel whose ions move down their electrochemical gradient.

Question: Study Guide Question: What is the role of caveolin in membrane structure and function? Answer: Caveolin organizes cholesterol-rich caveolae and promotes membrane curvature, contributing to membrane trafficking and signaling.

Question: What are caveolae? Answer: Small, flask-shaped plasma-membrane invaginations enriched in cholesterol and associated with caveolin. They participate in membrane organization, trafficking, and signaling.

Question: How does caveolin help curve a membrane? Answer: Its hydrophobic region inserts into the cytoplasmic leaflet → palmitoyl groups strengthen membrane association → caveolin molecules oligomerize and interact with cholesterol → unequal organization of the leaflets favors inward membrane curvature and caveolar organization.

Question: What membrane orientation is the main structural association for caveolin? Answer: A membrane-associated hairpin with both amino and carboxyl termini facing the cytoplasm. Its hydrophobic region associates with the cytoplasmic leaflet and helps organize caveolae.

Question: Study Guide Question: What structural features contribute to potassium channel selectivity? Answer: A narrow, conserved selectivity filter formed by four subunits positions backbone carbonyl oxygens to coordinate dehydrated K⁺ precisely.

Question: How does the tetrameric structure of a potassium channel create a selective pore? Answer: Four subunits contribute equivalent pore-loop regions around a central axis, producing a symmetric filter with multiple K⁺ coordination sites.

Question: How does the potassium-channel pore support rapid K⁺ conduction? Answer: Hydrated K⁺ enters the wide aqueous vestibule → pore-helix dipoles help stabilize the cation → K⁺ dehydrates at the filter → successive oxygen-lined binding sites stabilize it → occupancy by additional K⁺ ions favors onward movement → K⁺ exits and is rehydrated. Transport is driven by the electrochemical gradient.

Question: Which conserved sequence is associated with the selectivity filter of many K⁺ channels? Answer: TVGYG is a characteristic conserved filter sequence. Its backbone geometry helps create the oxygen-lined K⁺-binding sites.

Question: Study Guide Question: What is the structure and function of aquaporins? Answer: Aquaporins are membrane water channels, usually tetramers whose individual subunits form selective pores for rapid passive water transport.

Question: What structural features allow aquaporins to conduct water selectively? Answer: Each typical aquaporin subunit has six membrane-spanning α-helices and two pore-forming half-helices containing conserved NPA motifs. A narrow hydrophilic pathway accommodates water while excluding most solutes.

Question: How do aquaporins transport water while preventing proton leakage? Answer: Water enters a narrow pore → moves largely in single file through hydrogen-bonding interactions → pore geometry and electrostatics orient water and interrupt a continuous proton-conducting arrangement → water exits on the opposite side. Net flow follows the water-potential gradient, and no ATP is consumed.

Question: What is the main transported substance associated with aquaporins on an exam? Answer: Water, moving passively according to an osmotic gradient. Some family members, called aquaglyceroporins, also transport glycerol or other small neutral solutes, but water transport is the central association.

Question: Study Guide Question: What are the characteristics of peripheral membrane proteins? Answer: They bind membrane surfaces or integral proteins through noncovalent interactions and can often be released by salt, pH changes, or chelating agents.

Question: Why can peripheral proteins often be removed without dissolving the lipid bilayer? Answer: Their attachment depends mainly on electrostatic interactions and hydrogen bonds, rather than extensive insertion into the hydrophobic membrane core.

Question: How can changing salt concentration or pH release a peripheral membrane protein? Answer: High ionic strength screens electrostatic attractions, or altered pH changes the ionization of interacting groups → protein–membrane interactions weaken → the protein dissociates into solution. Chelators can release proteins whose association requires metal ions.

Question: What is the main attachment distinction between peripheral and lipid-anchored membrane proteins? Answer: Peripheral proteins associate through noncovalent surface interactions; lipid-anchored proteins carry a covalently attached lipid that inserts into the membrane. The lipid anchor is the key defining feature of the latter group.

Question: Study Guide Question: How do bacteria adjust membrane fluidity at lower temperatures? Answer: They increase low-melting membrane lipids, commonly by increasing cis-unsaturation and sometimes shortening or branching fatty acid chains.

Question: Why do cis double bonds help preserve fluidity at low temperature? Answer: Cis double bonds introduce bends that prevent neighboring acyl chains from aligning closely. Reduced packing weakens collective interactions that otherwise favor solidification.

Question: What is the membrane-level sequence of cold adaptation in bacteria? Answer: Cooling initially increases membrane order → lipid-synthetic or modifying activities change → lower-melting fatty acyl species become more abundant in phospholipids → tight packing decreases → membrane fluidity moves back toward a functional range. The particular enzymes vary by bacterial species.

Question: What is the main mechanism to associate with bacterial membrane-fluidity regulation? Answer: Changing fatty acid composition, especially the degree of cis-unsaturation. Chain length and branching also matter; most bacteria do not rely on cholesterol as animal cells do.

Question: Study Guide Question: What factors increase the fluidity of a lipid bilayer? Answer: Higher temperature, shorter acyl chains, and more cis-unsaturated chains; cholesterol can preserve fluidity at low temperatures.

Question: Why do shorter fatty acyl chains increase membrane fluidity? Answer: Shorter chains have fewer opportunities for favorable van der Waals interactions, so less energy is required to disrupt their packing.

Question: How does cholesterol buffer membrane fluidity across temperatures? Answer: At higher temperatures, its rigid rings restrict nearby acyl-chain motion → excessive fluidity decreases. At lower temperatures, cholesterol disrupts regular packing of saturated chains → crystallization is inhibited and fluidity is preserved. Its effect depends on temperature and lipid composition.

Question: Which double-bond geometry is most strongly associated with increased membrane fluidity? Answer: Cis double bonds, because their bends disrupt tight packing. Trans double bonds leave chains relatively straight and therefore produce less disruption.

Question: Study Guide Question: What determines the direction of ion movement through ion channels? Answer: The ion’s electrochemical gradient, which combines its concentration gradient with the membrane electrical potential.

Question: What is an electrochemical gradient? Answer: The combined chemical and electrical driving force on an ion. Concentration differences favor diffusion, while voltage attracts or repels ions according to their charge.

Question: How can the free-energy change for ion movement predict its direction? Answer: For movement from side 1 to side 2: ΔG = RT ln([ion]₂/[ion]₁) + zF(ψ₂ − ψ₁). R is the gas constant, T absolute temperature, z ion charge, F Faraday’s constant, and ψ electrical potential. Net passive movement favors the direction with ΔG < 0.

Question: What happens when a channel opens while the membrane potential equals that ion’s equilibrium potential? Answer: There is no net ion flux driven through that channel. Electrical and chemical forces balance, although individual ions may still move in both directions.

Question: Study Guide Question: What is the role of SNARE proteins in membrane dynamics? Answer: They recognize and bring compatible vesicular and target membranes together to promote membrane fusion.

Question: Why is membrane fusion difficult without specialized proteins? Answer: Membrane surfaces are hydrated and resist close approach, while fusion requires substantial lipid rearrangement. SNARE assembly supplies favorable binding energy that helps overcome these barriers.

Question: How does SNARE zippering bring membranes together? Answer: A vesicular SNARE engages target-membrane SNAREs → their helices assemble progressively from membrane-distal toward membrane-proximal regions → zippering draws the membranes into close apposition → lipid rearrangement and fusion-pore formation become favorable.

Question: What do v-SNARE, t-SNARE, R-SNARE, and Q-SNARE mean? Answer: v-SNARE and t-SNARE describe vesicle versus target-membrane location. R-SNARE and Q-SNARE describe a conserved central Arg or Gln residue. Neuronal synaptobrevin is an R-SNARE; syntaxin and SNAP-25 contribute Q-SNARE helices.

Question: Study Guide Question: What process is directly mediated by SNARE proteins? Answer: Membrane fusion, including fusion of neurotransmitter-containing vesicles with the presynaptic plasma membrane.

Question: How does membrane fusion differ from membrane fission? Answer: Fusion joins two membranes and can connect their compartments; fission separates one membrane into distinct membrane-bound structures. SNAREs directly promote fusion.

Question: What sequence connects SNARE-mediated fusion to exocytosis? Answer: Secretory vesicle approaches the plasma membrane → docking and priming occur → SNARE assembly brings the bilayers together → a fusion pore connects vesicle lumen to extracellular space → vesicle contents are released. The vesicle membrane becomes continuous with the plasma membrane.

Question: What is the main process to select when an exam asks about SNARE function? Answer: Vesicle–target membrane fusion. Neurotransmitter synthesis, vesicular loading, and Ca²⁺ sensing involve other components; SNAREs supply the fusion machinery.

Question: Study Guide Question: What drives facilitated diffusion through biological membranes? Answer: A downhill concentration gradient for neutral solutes or an electrochemical gradient for ions.

Question: Why can a facilitated-diffusion protein accelerate transport without supplying energy? Answer: It lowers the activation barrier for membrane crossing, allowing the existing gradient to drive faster movement without changing the equilibrium distribution.

Question: What happens to net facilitated diffusion as a system approaches equilibrium? Answer: The driving gradient decreases → forward and reverse fluxes approach equality → net flux falls to zero at equilibrium. Transport proteins remain capable of exchanging molecules in both directions.

Question: What is the main distinction between the driving force and transport capacity in facilitated diffusion? Answer: The gradient determines net direction; transporter abundance affects transport capacity. Adding transporters can increase the rate but cannot drive independent uphill accumulation.

Question: Study Guide Question: What is the ion exchange and energy conversion in Na⁺/K⁺ ATPase? Answer: One ATP hydrolyzed drives 3 Na⁺ out and 2 K⁺ in, converting ATP chemical energy into electrochemical gradients.

Question: Why is the Na⁺/K⁺ ATPase electrogenic? Answer: It moves three positive charges out for every two moved in, producing a net outward transfer of one positive charge per cycle.

Question: What is the complete basic transport cycle of the Na⁺/K⁺ ATPase? Answer: Inward-facing E1 binds 3 cytosolic Na⁺ → MgATP phosphorylates a conserved Asp and releases ADP → conversion to E2-P exposes the sites outward and releases 3 Na⁺ → 2 extracellular K⁺ bind → dephosphorylation releases Pi → return to E1 exposes the sites inward → 2 K⁺ are released. Net: ATP + H₂O + 3 Na⁺in + 2 K⁺out → ADP + Pi + 3 Na⁺out + 2 K⁺in.

Question: How does the Na⁺/K⁺ ATPase support secondary active transport? Answer: It stores ATP-derived energy in the Na⁺ gradient. Na⁺ movement back into the cell can then drive uphill cotransport or exchange of another solute.

Question: Study Guide Question: How many amino acids are needed to span a membrane bilayer in an α-helix? Answer: Approximately 20 predominantly hydrophobic amino acids, often about 20–25 residues.

Question: How is the required length of a membrane-spanning α-helix estimated? Answer: An α-helix rises about 1.5 Å per residue, and the bilayer’s hydrophobic core is about 30 Å thick. Therefore, approximately 30/1.5 = 20 residues are needed.

Question: How does an α-helix allow a peptide backbone to cross the hydrophobic membrane interior? Answer: Backbone C=O and N–H groups form internal hydrogen bonds → polar backbone groups are largely satisfied within the helix → hydrophobic side chains face surrounding lipids → the segment can remain stable in the membrane core.

Question: What amino acid property is the main exam association for a membrane-spanning α-helix? Answer: A stretch of approximately 20 predominantly hydrophobic residues. Some polar residues may face an internal pore or other helices, but lipid-facing surfaces are generally hydrophobic.

Question: Study Guide Question: What type of bond links a palmitoyl anchor to a protein? Answer: Typically a thioester bond to the sulfhydryl group of a cysteine residue.

Question: What is S-palmitoylation? Answer: Covalent attachment of a 16-carbon palmitoyl group to a cysteine sulfur through a thioester linkage. This increases a protein’s membrane affinity and is often reversible.

Question: How is a typical palmitoyl anchor attached and removed? Answer: Palmitoyl-CoA donates its acyl group → a protein acyltransferase transfers it to protein–Cys–SH → an S-palmitoylated cysteine thioester forms and CoA is released. Acyl-protein thioesterases can hydrolyze the thioester, releasing the fatty acid and regenerating the cysteine thiol.

Question: How does a palmitoyl anchor differ chemically from a prenyl anchor? Answer: Palmitoyl anchors typically use a hydrolyzable thioester bond; prenyl anchors use a thioether bond to cysteine. A thioester contains a carbonyl adjacent to sulfur; a thioether does not.

Question: Study Guide Question: What type of bond links a myristoyl anchor to a protein? Answer: An amide bond, usually to the α-amino group of an N-terminal glycine.

Question: What is N-myristoylation? Answer: Attachment of a 14-carbon myristoyl group to a protein’s N-terminal amino group, typically on glycine. The amide-linked fatty acid promotes membrane association.

Question: How is an N-myristoyl anchor formed? Answer: An N-terminal glycine is exposed, commonly after initiator methionine removal → N-myristoyltransferase transfers myristate from myristoyl-CoA to the glycine α-amino group → an amide bond forms and CoA is released. This generally produces a more stable linkage than reversible S-palmitoylation.

Question: What three features should be linked together for myristoylation on an exam? Answer: Myristate = 14 carbons; attachment site = N-terminal glycine; bond = amide. Contrast this with palmitate = 16 carbons; cysteine; thioester.

Question: Study Guide Question: What increases lipid fluidity in the interior of a bilayer? Answer: Cis-unsaturated and shorter fatty acyl chains, which disrupt packing and weaken interactions between neighboring tails.

Question: Why is the bilayer interior especially sensitive to fatty acyl-chain composition? Answer: The interior consists primarily of hydrocarbon chains. Their length, saturation, and geometry determine packing, intermolecular contacts, and freedom of motion.

Question: How does introducing a cis double bond alter the bilayer interior? Answer: A cis double bond creates a persistent bend → neighboring chains cannot align as closely → packing becomes less regular → the ordered phase is destabilized → fluidity increases at a given temperature.

Question: What is the main reason a cis double bond increases membrane fluidity? Answer: Its bend disrupts close packing of neighboring fatty acyl chains. The double bond itself restricts rotation; increased fluidity comes from reduced collective packing.

Question: Study Guide Question: Which SERCA pump conformation has higher affinity for Ca²⁺? Answer: E1, whose Ca²⁺-binding sites face the cytosol.

Question: Why must SERCA alternate between high- and low-affinity Ca²⁺ states? Answer: High-affinity E1 captures Ca²⁺ at low cytosolic concentrations; low-affinity E2-P releases it into the Ca²⁺-rich ER lumen. ATP-driven conformational changes couple these opposite requirements.

Question: How does phosphorylation change SERCA’s Ca²⁺-binding behavior? Answer: E1 binds 2 Ca²⁺ → MgATP phosphorylates Asp-351 → the pump undergoes an occluded transition → E2-P exposes the sites to the lumen with lower affinity → Ca²⁺ dissociates. Dephosphorylation returns the pump toward E1.

Question: Which SERCA state releases Ca²⁺ toward the ER lumen? Answer: The low-affinity, lumen-facing E2-P state. The high-affinity E1 state binds Ca²⁺ from the cytosol.

Question: Study Guide Question: Why do saturated fatty acids have higher melting points than unsaturated ones? Answer: Their straighter chains pack more tightly and make stronger collective van der Waals contacts than comparable cis-unsaturated chains.

Question: How does fatty acid packing determine melting temperature? Answer: More favorable interactions stabilize the ordered solid state, so more thermal energy is needed to disrupt it. Tight packing therefore generally raises melting temperature.

Question: What physical changes occur when a saturated fatty acid assembly melts? Answer: Heating increases molecular motion → thermal energy overcomes the collective stabilization of ordered packing → chains adopt more disordered conformations → the assembly becomes liquid. Covalent carbon–carbon bonds remain intact.

Question: What is the main melting-point comparison to remember for saturated versus unsaturated fatty acids? Answer: At the same chain length, saturated fatty acids generally have higher melting points than cis-unsaturated fatty acids. Chain length and trans geometry can change comparisons between different molecules, but tight packing of saturated chains is the main tested explanation.

Question: Study Guide Question: Which lipid acts as an “eat-me” signal during apoptosis? Answer: Phosphatidylserine exposed on the outer leaflet of the plasma membrane.

Question: Why does external phosphatidylserine signal that a cell should be engulfed? Answer: Phosphatidylserine is normally concentrated on the cytosolic leaflet. Its exposure outside provides a recognition signal for phagocytes and helps mark apoptotic cells for clearance.

Question: How does apoptosis produce an external phosphatidylserine signal? Answer: Apoptotic signaling activates lipid-scrambling activity and inhibits maintenance of inward PS asymmetry → PS becomes exposed on the outer leaflet → phagocytes recognize exposed PS directly or through bridging molecules → the cell is engulfed.

Question: What change in phosphatidylserine is the main exam association with apoptosis? Answer: Redistribution from the inner leaflet to the outer leaflet. The signal depends on external exposure of PS, rather than conversion into a different lipid.

Question: Study Guide Question: How do BAR domain proteins induce membrane curvature? Answer: Their curved, membrane-binding domains scaffold the bilayer into a matching shape; some also insert amphipathic helices into one leaflet.

Question: What is a BAR domain? Answer: A membrane-binding structural domain, named for Bin, amphiphysin, and Rvs proteins, that commonly forms curved dimers. Its shape and charged surface support membrane-curvature sensing and generation.

Question: How can a BAR-domain protein bend a membrane? Answer: A positively charged curved surface binds acidic membrane lipids → the protein scaffolds the bilayer along its curvature → assembly of additional proteins reinforces bending. In some BAR-family proteins, amphipathic-helix insertion expands one leaflet locally and further promotes curvature.

Question: What is the main mechanism to associate with BAR-domain proteins on an exam? Answer: Curved protein scaffolds bind membranes and impose or stabilize curvature. Different BAR-family proteins favor different geometries, and some additionally use amphipathic-helix insertion.

Question: Study Guide Question: Where are GPI-anchored proteins typically localized? Answer: On the extracellular face of the plasma membrane, attached to the outer leaflet by a glycosylphosphatidylinositol anchor.

Question: What is a GPI anchor? Answer: A glycolipid-based anchor containing phosphatidylinositol, a carbohydrate linker, and phosphoethanolamine that links to a protein’s carboxyl terminus. Its lipid portion inserts into the membrane.

Question: How does GPI anchoring establish extracellular protein orientation? Answer: A protein enters the ER lumen → a C-terminal targeting segment is replaced by a preassembled GPI anchor → the lipid enters the lumen-facing leaflet → vesicular trafficking preserves topology → the protein appears on the extracellular plasma-membrane surface.

Question: Which surface generally contains GPI anchors versus palmitoyl and myristoyl anchors? Answer: GPI anchors generally attach proteins to the extracellular surface; palmitoyl and myristoyl anchors commonly support association with the cytoplasmic surface.

Question: Study Guide Question: Which lipid supports mitochondrial cristae formation? Answer: Cardiolipin, a cone-shaped phospholipid enriched in the inner mitochondrial membrane.

Question: What structural feature makes cardiolipin well suited to curved mitochondrial membranes? Answer: Its relatively small polar region and four fatty acyl chains produce a shape that favors membrane curvature. Its interactions with inner-membrane proteins also support crista organization.

Question: How does cardiolipin contribute to mitochondrial structure and energy metabolism? Answer: Cardiolipin becomes enriched in the inner membrane → its geometry supports curved membrane regions → interactions stabilize respiratory complexes and their organization → efficient electron transport and maintenance of the proton gradient support ATP synthesis. Cristae architecture also depends on protein complexes.

Question: How many fatty acyl chains does a cardiolipin molecule contain? Answer: Four. It consists of two phosphatidyl groups linked through a central glycerol, unlike ordinary diacyl glycerophospholipids with two chains.

Question: Study Guide Question: What characterizes the liquid-ordered (Lo) membrane phase? Answer: Relatively ordered, tightly packed acyl chains with retained lateral fluidity, commonly associated with cholesterol and saturated sphingolipids.

Question: How does a liquid-ordered phase differ from liquid-disordered and gel phases? Answer: Lo combines substantial acyl-chain order with liquid-like lateral mobility; Ld has more disordered chains; a true gel phase strongly restricts lipid mobility. Some introductory source descriptions use “gel-like” loosely for ordered states.

Question: How does cholesterol favor liquid-ordered membrane organization? Answer: Cholesterol’s rigid rings align with nearby hydrocarbon chains → chain conformational freedom decreases and order increases → cholesterol also disrupts regular crystalline packing → an ordered but laterally mobile phase can form.

Question: What membrane organization is the main exam association for lipid rafts? Answer: A relatively ordered, cholesterol- and sphingolipid-rich domain, commonly associated with the liquid-ordered phase. Rafts remain dynamic; “ordered” primarily refers to acyl-chain organization.

Question: Study Guide Question: Which disorder is caused by mutations in the cardiolipin remodeling enzyme tafazzin? Answer: Barth syndrome, an X-linked disorder associated with cardiomyopathy, skeletal myopathy, and neutropenia.

Question: What is tafazzin’s normal biochemical function? Answer: Tafazzin is a phospholipid transacylase involved in cardiolipin remodeling. It redistributes fatty acyl groups to help establish the appropriate cardiolipin molecular composition.

Question: How can tafazzin deficiency impair mitochondrial function? Answer: TAZ mutation → defective cardiolipin acyl remodeling → abnormal cardiolipin composition and accumulation of monolysocardiolipin → impaired inner-membrane organization and respiratory-complex function → inefficient energy production and increased oxidative stress. High-energy tissues such as cardiac and skeletal muscle are particularly affected.

Question: What biochemical function is the main exam association for tafazzin? Answer: Cardiolipin acyl-chain remodeling after initial cardiolipin synthesis. Its effects on ATP production are downstream consequences of maintaining proper inner-membrane lipid composition.

Question: Study Guide Question: How are bile acids classified among lipid types? Answer: Sterol lipids: amphipathic, steroid-derived products of cholesterol metabolism.

Question: Why are bile acids classified as sterol-derived lipids rather than fatty acids? Answer: They retain the characteristic fused steroid-ring framework derived from cholesterol. Their carboxyl group does not make them ordinary long-chain fatty acids.

Question: How do bile acids assist dietary lipid digestion and absorption? Answer: Cholesterol-derived bile acids are commonly conjugated with glycine or taurine → bile salts enter the intestine → their amphipathic surfaces promote emulsification and mixed-micelle formation → lipid-digestion products and fat-soluble vitamins become more accessible for absorption. Bile salts assist pancreatic lipases but do not themselves hydrolyze triacylglycerols.

Question: What is the distinction between a bile acid and a bile salt? Answer: A bile acid is the cholesterol-derived acid; a bile salt is its ionized form, commonly after glycine or taurine conjugation. At intestinal pH, many conjugated bile acids occur predominantly as salts.

Question: Study Guide Question: How is anandamide synthesized from phosphatidylethanolamine? Answer: Phosphatidylethanolamine is N-arachidonoylated to form NAPE, which NAPE-specific phospholipase D cleaves to release anandamide.

Question: What are anandamide and its immediate phospholipid precursor? Answer: Anandamide is N-arachidonoylethanolamine, an endocannabinoid. Its immediate precursor in the NAPE-PLD pathway is N-arachidonoyl phosphatidylethanolamine, a form of NAPE.

Question: What is the NAPE-PLD pathway for anandamide synthesis and degradation? Answer: An arachidonoyl group is transferred from a donor phospholipid to the amino group of phosphatidylethanolamine by N-acyltransferase activity → N-arachidonoyl phosphatidylethanolamine forms → NAPE-specific phospholipase D hydrolyzes it with H₂O → anandamide + phosphatidic acid. Termination: anandamide + H₂O → arachidonic acid + ethanolamine, catalyzed by fatty acid amide hydrolase, FAAH. This route does not require NADH or NADPH.

Question: How does anandamide synthesis differ from 2-arachidonoylglycerol synthesis? Answer: Anandamide can arise through NAPE and NAPE-PLD; 2-AG arises from arachidonoyl-containing diacylglycerol through diacylglycerol lipase. PLC can generate that diacylglycerol from membrane phosphoinositides. Both are endocannabinoids, but they have different precursor pathways.

Question: Study Guide Question: How do archaeal membrane lipids differ from bacterial lipids? Answer: Archaeal lipids typically contain ether-linked, branched isoprenoid chains on glycerol-1-phosphate; bacterial lipids typically contain ester-linked fatty acids on glycerol-3-phosphate.

Question: What are the major chemical distinctions between typical archaeal and bacterial membrane lipids? Answer: Ether versus ester linkages; branched isoprenoid versus fatty acyl chains; and opposite glycerol-phosphate stereochemistry. Some archaeal tetraether lipids also span the membrane to form a monolayer.

Question: How can archaeal tetraether lipids form a membrane-spanning monolayer? Answer: Long isoprenoid chains are ether-linked to glycerol-containing polar groups at both ends → each lipid extends across the membrane → polar ends contact water on opposite surfaces → a continuous monolayer forms instead of two independent leaflets. This architecture can increase membrane stability.

Question: What is the main exam distinction for archaeal membrane lipids, and where do tetraether monolayers fit? Answer: Archaea characteristically have ether-linked, branched isoprenoid chains on glycerol-1-phosphate. Some form tetraether monolayers, while others form diether bilayers. Ether versus ester linkage is the main basic comparison with bacteria, although ether lipids also occur elsewhere.

Question: Study Guide Question: What are the factors that increase the melting point of a lipid? Answer: Longer hydrocarbon chains, greater saturation, and straighter chains that pack efficiently generally increase melting point.

Question: Why do longer and more saturated lipid chains generally melt at higher temperatures? Answer: Longer chains make more van der Waals contacts, and saturated chains align more efficiently. These interactions stabilize ordered packing, requiring more heat to disrupt it.

Question: How do chain length and double-bond geometry alter a lipid’s melting transition? Answer: Longer chains or replacement of cis-unsaturated chains with straight saturated or trans-containing chains → closer packing and stronger collective interactions → greater stabilization of the ordered phase → higher temperature required for melting. More cis unsaturation generally produces the opposite effect.

Question: Which factors should receive first priority when predicting lipid melting point on an exam? Answer: Chain length and degree of cis-unsaturation: longer chains and fewer cis double bonds generally increase melting point. Double-bond geometry, branching, head-group interactions, and mixture composition also matter, but length and saturation are the main starting comparisons.