Biochem II Exam 4 Study Guide

how does increasing temperature affect membrane lipid organization?

Increasing temperature generally increases membrane fluidity by disrupting the packing of lipid molecules, leading to more disorder in the lipid bilayer.

what are the structural and functional characteristics of membrane proteins?

Membrane proteins are amphipathic molecules that can be either integral or peripheral. They play crucial roles in transport, signaling, and maintaining the structure of the cell membrane.

what type of transport is involved in glucose uptake by erythrocytes?

Facilitated diffusion (passive transport) mediated by the GLUT1 uniporter/carrier protein

how does GLUT1 work?

GLUT1 undergoes a series of conformational changes. It alternates between states exposing a glucose-binding site to either the outside or the inside of the cell based on concentration gradient of glucose (glucose binds on the uniporter and conformational changes occur).

how do membrane compositions differ between inner and outer mitochondrial membranes?

The outer mitochondrial membrane (OMM) has a ≈1:1 protein-to-lipid ratio and contains porins that make it permeable to small molecules. The inner mitochondrial membrane (IMM) is highly protein-dense (≈3:1 or 75% protein), strictly impermeable to ions (H+H+) to maintain the proton gradient, and uniquely enriched in cardiolipin to stabilize respiratory chain complexes.

how can integral membrane proteins be extracted from membranes?

Using amphipathic detergents (such as Triton X-100, SDS, or octyl glucoside) or organic solvents to disrupt hydrophobic interactions in the lipid bilayer and solubilize the proteins.

what determines the potassium channel’s selectivity for K+ over NA+?

A selectivity filter lined with backbone carbonyl oxygens precisely mimics the hydration shell of K+, allowing it to shed its water shell. Because Na+ is too small to coordinate properly with these oxygens (not able to come into contact), the energetic cost of shedding its water shell is unfavorable.

how do bacteria adapt their membrane composition to colder temperatures?

Bacteria incorporate a higher proportion of fatty acids containing cis-double bonds. These double bonds introduce kinks that prevent tight packing, favoring the fluid liquid-disordered (Ld) state and lowering the transition temperature (Tm​).

what is the transport kinetics of GLUT1 in erythrocytes?

GLUT1 exhibits saturation kinetics analogous to Michaelis-Menten enzymes

what type of transport systems moves CA2+ into the ER against its gradient?

P-type ATPases, specifically the SERCA (Ca2+-ATPase) pump

which choline-containing lipids are found in the outer leaflet of plasma membranes?

Phosphatidylcholine (PC) and sphingomyelin (SM)

which membrane transport processes do not require protein facilitators?

Simple/passive diffusion

are flippases and floppases considered facilitated transport systems?

No, they are active transport systems (P-type ATPases and ABC transporters) that consume ATP to move lipids across leaflets.

what do flippases do?

aka P-type ATPases; they transport amino-phospholipids (PE & PS) from the OUTER to the CYTOSOLIC leaflet (consumes ~1 ATP per molcule)

what do floppases do?

aka ABC transporters; they transport phospholipids and sterols from the CYTOSOLIC to the OUTER leaflet (ATP-dependent)

what are the common components of biological membranes?

Lipids and proteins (along with carbohydrates)

what are the general features of lipid bilayers in biological membranes?

They are formed by amphipathic molecules with cylindrical geometries, hide their hydrophobic tails internally away from water, and display membrane asymmetry

what are the key features of the fluid mosaic model of membranes?

Individual lipids and proteins form a mobile, fluid pattern with rapid lateral diffusion and slow transverse flip-flop motion.

what are integrins and what is their role in membranes?

Integrins are heterodimeric (αβ) cell adhesion molecules (CAMs) that link cells to the extracellular matrix or other cells.

how do ligand-gated ion channels function in membranes?

They act as rapid, non-saturable aqueous pores that open or close in response to the binding of specific chemical ligands.

what does a hydropathy plot reveal about membrane proteins?

It displays free-energy changes of amino acid transfer to predict transmembrane α-helices (peaks > 0)

which molecules are typically enriched in lipid rafts?

Sphingolipids and cholesterol

what is the mechanism of facilitated diffusion across membranes?

Downhill movement assisted by integral membrane proteins (carriers or channels) that reduce activation energy (ΔG*)

what enzyme class does the F-type ATPase belong to?

Proton-driven ATP synthases in mitochondria and chloroplasts

what proteins mediate fusion of vesicular membrane during neurotransmitter release?

SNARE proteins (specifically v-SNAREs on the vesicle and t-SNAREs on the target membrane). These proteins zip together to draw the membranes into close contact and open a fusion pore

what types of molecules are transported by ABC transporters?

diverse substrates, including drugs, lipids (such as phospholipids and sterols), and ions.

what is the role of caveolin in membrane structure and function?

Caveolin forms flask-shaped membrane invaginations (caveolae) that flatten in response to mechanical stress to buffer membrane tension.

what structural features contribute to potassium channel selectivity?

A narrow selectivity filter containing the TVGYG sequence with backbone carbonyl oxygens spaced precisely to coordinate K+ ions while excluding smaller Na+ ions.

what is the structure and function of aquaporins?

Tetrameric channels featuring NPA motifs that form a size-exclusion pore and electrostatic barrier to conduct water rapidly while excluding protons.

what are the characteristics of peripheral membrane proteins?

They associate loosely via electrostatic interactions and hydrogen bonding, and are released by changes in pH, chelating agents, urea, or carbonate

how do bacteria adjust membrane fluidity at lower temperatures?

incorporating a higher proportion of fatty acids containing cis-double bonds. These double bonds introduce kinks that prevent tight molecular packing, which favors the fluid liquid-disordered (Ld) state and lowers the transition temperature (Tm).

what factors increase the fluidity of a lipid bilayer?

The presence of unsaturated fatty acids (introducing cis-double bonds and kinks that prevent tight packing) and lower amounts of cholesterol at cool temperatures.

what determines the direction of ion movement through ion channels?

The electrochemical gradient, which combines the chemical concentration gradient and the electrical membrane potential (Vm)

what is the role of SNARE proteins in membrane dynamics?

They zip together from their amino termini to draw membranes into close apposition, driving hemifusion and opening a fusion pore.

what process is directly mediated by SNARE proteins?

intracellular membrane fusion

what drives facilitated diffusion through biological membranes?

The solute's electrochemical concentration gradient (downhill movement)

what is the ion exchange and energy conversion in NA+/K+ ATPase?

It hydrolyzes ATP to actively pump 3 NA+ ions out of the cell and 2 K+ ions into the cell.

how many amino acids are needed to span a membrane bilayer in an α-helix?

Approximately 20 amino acid residues.

what type of bond links a palmitoyl anchor to a protein?

a thioester bond

what type of bond links a myristoyl anchor to a protein?

an amide bond

what increases lipid fluidity in the interior of a bilayer?

Unsaturated fatty acyl chains with cis-double bonds.

which SERCA pump conformation has higher affinity for Ca2+?

Specific conformational states linked to P-type ATPase catalytic cycles involving phosphorylated aspartate intermediates (E-P)

why do saturated fatty acids have higher melting points than unsaturated ones?

Their straight hydrocarbon tails pack tightly into an ordered (Lo) state, requiring more thermal energy; melting points increase with longer hydrocarbon chain lengths and higher degrees of saturation

which lipid acts as an “eat-me” signal during apoptosis?

Phosphatidylserine (PS)

how do BAR domain proteins induce membrane curvature?

By acting as banana-shaped, positively charged dimers that bind and stabilize curved membranes or insert amphipathic helices to force bending

where are the GPI-anchored proteins typically localized?

Exclusively on the outer face/leaflet of the plasma membrane, facing the extracellular environment.

which lipid supports mitochondrial cristae formation?

Cardiolipin (CL)

what characterizes the liquid-ordered (Lo) membrane phase?

A gel-like, tightly packed state with restricted molecular motion.

which disorder is caused by mutations in the cardiolipin remodeling enzyme tafazzin?

Barth syndrome

how are bile acids classified among lipid types?

As polar derivatives of cholesterol.

how is anandamide synthesized from phosphatidylethanolamine?

Anandamide functions as an endocannabinoid lipid messenger derived via specialized membrane lipid pathways.

how do archaeal membrane lipids differ from bacterial lipids?

Archaea use sn-glycerol-1-phosphate, branched isoprenoid chains, and ether linkages

what are the factors that increase the melting point of a lipid?

• Longer hydrocarbon chain lengths, which increase intermolecular interactions and require more thermal energy to disrupt.

• Higher degrees of saturation (fewer or no double bonds), which allow the straight hydrocarbon tails to pack tightly together into an ordered (Lo) state

linoleic acid

aka omega-6; one of the essential fatty acids that the body cannot produce; primarily gives rise to pro-inflammatory eicosanoids (INCREASES INFLAMMATION)

a-linoleic acid

aka omega-3; one of the essential fatty acids that the body cannot produce; produces anti-inflammatory cytokines and pro-resolving mediators, converted into EPA and DHA (DECREASES INFLAMMATION)

where are triglycerides/triglycerols stored?

in adipose tissue (animals) or seeds (plants) as anhydrous lipid droplets

what is the advantage of triglycerides/triglycerols?

its highly reduced state yields more energy per gram than carbohydrates, provides thermal insulation in polar animals (seals, whales, hibernating bears, etc)

what is partial hydrogenation?

it converts liquid vegetable oils into solid/semi-solid fats by saturating double bonds (increases melting point & shelf life) but can also produce harmful trans fatty acids

what does trans fatty acids do?

raise LDL cholesterol, lower HDL, and increase inflammation/cardiovascular diseases risk

what is lipid oxidation?

aka rancidity; polyunsaturated fatty acids are susceptible to free radical attack at methylene interrupter groups forming lipid peroxides and volatile, foul-smelling aldehydes

what do antioxidants do?

prevent oxidation by scavenging radicals or chelating metal catalysts

what are the common head groups of glycerophospholipids?

PE, PC, PS, PG, PI/PIP/PIP2, cardiolipin

what are glycerophospholipids?

two fatty acids ester-linked to C-1 and C-2 of glycerol; a polar head group attached via phosphodiester bond at C-3

what does plasmalogens do?

act as endogenous cellular antioxidants protecting membranes from oxidative damage; deficiencies cause Rhizomelic Chondrodysplasia Punctata (RCDP)

what does Platelet-Activating Factor (PAF) do?

potent proinflammatory ether lipid mediator stimulating platelet aggregation, inflammation and anaphylaxis

what are glycolipids?

contains sugar residues instead of a phosphate groups (ex: sphingolipids & plant galactolipids)

what are archaeal tetraether lipids?

branched isoprenoid chains (prevents twists & turns, increases stability) ether-linked to glycerol monolayers/bilayers providing extreme environmental stability

what are sterols?

rigid system of four fused hydrocarbon rings (cholesterol is the major animal sterol and membrane stabilizer)

how does cholesterol affect the lipid membrane fluidity?

at high temps, cholesterol decreases membrane fluidity (more rigidity) when the membrane is too fluid; at low temps, cholesterol increases membrane fluidity (less rigidity) when the membrane is too rigid

what is a sphingolipid?

derivatives of sphingosine that lacks glycerol

what are the classes of sphingolipids?

sphingomyelins, cerebrosides, globosides, and gangliosides [all share a common sphingosine backbone but differ in polar heads]

what is lysosomal storage disease?

genetic deficiencies in lysosomal hydrolytic enzymes cause fatal pathological accumulations of sphingolipids/gangliosides (ex: Tay-sachs, Sandhoff, Gaucher, Niemann-Pick, Fabry disease)

how does S1P relate to multiple sclerosis?

multiple sclerosis (MS) is a condition in which autoreactive lymphocytes attack the myelin sheath. Sphingosine 1-phosphate (S1P) is a lipid mediator that regulates lymphocyte trafficking and allows lymphocytes out the lymph nodes). Drugs like fingolimod and siponimod act as S1P receptor modulators (inhibit S1P). By modulating S1P receptors, these medications work by sequestering autoreactive lymphocytes in the lymph nodes, preventing them from entering circulation and attacking the myelin sheath.

what is the structure of isoprenes?

they are built from 5-carbon isoprene units linked head to tail; they give rise to diverse secondary metabolites

what are steroid hormones?

oxidized cholesterol derivatives lacking alkyl tails that act as endocrine signals regulating metabolism, salt balance and reproduction

what are bile acids?

polar derivatives of cholesterol synthesized in the liver, conjugated with taurine or glycine to form bile salts and stored in the gall bladder; its amphipathic structure allows them to emulsify dietary fats in the intestine to facilitate digestion

what are plant sterols & stanols (PSS)?

they structurally mimic cholesterol, competitively blocking its intestinal absorption and significantly lowering plasma LDL cholesterol

what are phospholipases?

they are enzymes that cleaves phospholipids to generate bioactive secondary messengers

PLA1/PLA2

hydrolyzes acyl chains at C-1 or C-2; PLA2 releases arachidonic acid (the rate limiting precursor for all eicosanoids)

what inhibits PLA2?

glucocorticoids to exert anti-inflammatory effects

PLC

hydrolyzes PIP2 in the plasma membrane into IP3 and diacylglycerol (DAGs)

PLD

cleaves phosphodiester bonds to generate phosphatidic acid

what are eicosanoids?

a diverse family of 20-carbon signaling molecules derived from the oxidation of polyunsaturated fatty acids (PUFAs)—most commonly arachidonic acid—that act as local hormones (autocrine and paracrine agents)

what are endocannabinoids?

lipid messengers like Anandamide (AEA) [responsible for pleasure and memory] and 2-Arachidonoylglycerol (2-AG) [responsible for managing pain and regulating immune function] mediate retrograde synaptic signaling by binding CB1/.CB2 receptors [they are made on the spot when needed and are degraded so it doesn’t overstimulate the body]

what is the hydrophobic effect?

when nonpolar hydrocarbons are mixed with water, they do not form a single solution: 2 phases form. Hydrophobic molecules interfere with water’s hydrogen bonding network. forcing surrounding water molecules to form highly ordered, cage-like structures

which choline-containing lipids are localized to the inner leaflet of plasma membranes?

phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositols (PII/PIP/PIP2)

what do scramblases do?

move any phospholipid down its concentration gradient in either direction towards equilibrium (ATP-independent, some require CA2+)

what are lipid transfer proteins (LTPs)?

soluble proteins with hydrophobic pockets that carry lipids directly between membrane compartments

what are amphitropic proteins?

associate reversibly with membranes and exist in both the cytosol and membranes

what are monotopic proteins?

interact with only a single leaflet of the membrane via small hydrophobic domains

what is the positive-inside rule?

positively charged amino acids (lys, his, arg) are more commonly found on the cytoplasmic side of the membrane and flanking regions of integral membrane proteins; these amino acids act as physical anchor pegs that ensure the protein folds and functions correctly and the active sites face the right way

which amino acid residues act as membrane interface anchors?

tryptophan and tyrosine

what do hydropathy index/plots show?

they express the free-energy change of transferring an amino acid side chain from a hydrophobic solvent to water. Hydropathy plots these value averages across a window of residues to predict transmembrane α-helices

lipid-anchored proteins are covalently attached to membrane lipids via?

GPI (glycosyl phosphatidylinositol) anchors, Amide-linked myristoyl, Thioester-linked fatty acyl (palmitoyl) and Thioether-linked prenyl (farnesyl/geranylgeranyl)

what are the phase states?

liquid-ordered (Lo), liquid-disordered (Ld) and transition temperature (Tm)

liquid-ordered (Lo) state

gel-like, tightly packed, low motion

liquid-disordered (Ld) state

fluid, constant lateral and rotational motion of hydrocarbon chains

transition temperature (Tm)

the temperature at which a membrane melts from a gel to a fluid state

what is Cholesterol’s Bidirectional Role?

cholesterol acts as a fluidity buffer. at high temps, it restrains phospholipid movement and stabilizes the membrane (Lo formation); at low temps, it disrupts close packing, preventing solidification

what are lipid rafts?

microdomains enriched in sphingolipids and cholesterol residing in a liquid-ordered (Lo) phase. they are thicker and more ordered than surrounding phospholipid-rich regions and serves as platforms that concentrate specific proteins to speed up signaling and compartmentalization reactions