bioch lec 6- bio membranes
What are lipids?
Mostly non-polar, hydrophobic, water-insoluble molecules. Includes fatty acids, triacylglycerols, membrane lipids, cholesterol. Typically contain fatty acids.
General structure of fatty acids
Long-chain hydrocarbon carboxylic acids, up to 24 carbons (16 & 18 most common). Amphipathic. Formula: CH₃(CH₂)ₙCOO⁻. Can be saturated or mono/polyunsaturated. Usually cis double bonds.
Effect of cis double bonds on fatty acid structure
Introduce kinks, lower melting point, prevent close packing. Most natural double bonds are cis. (Image on page 3 shows this clearly.)
Shorthand fatty acid notation
(# carbons):(# double bonds)Δ(position)
Example: 16:1Δ⁷ = 16 carbons, 1 double bond at C7.
ω, α, β carbon positions
ω (omega): last carbon (methyl end).
α: first carbon after carbonyl.
β: next after α.
Cis vs trans double bonds
Cis: bent → lower melting point, low packing.
Trans: straighter → pack like saturated fats → higher melting point.
Factors affecting fatty acid melting point
Chain length: ↑ length → ↑ melting temp.
Unsaturation: ↑ unsaturation → ↓ melting temp (stronger effect than length).
Why do unsaturated fatty acids pack poorly?
The bend in cis double bonds disrupts van der Waals interactions → lower melting point. Trans fatty acids pack better than cis.
What are triacylglycerols (TAGs)?
Storage molecules for fatty acids, extremely hydrophobic, composed of glycerol + 3 fatty acyl esters. Mixed TAGs are common.
Factors affecting TAG melting point
TAGs melt lower when they contain shorter or more unsaturated fatty acids.
Three major classes of membrane lipids
Glycerophospholipids
Sphingolipids
Cholesterol
All are amphipathic (large polar head + hydrophobic tails).
Why glycerophospholipids form membranes but TAGs do not
TAGs lack a polar head group (fully hydrophobic), while glycerophospholipids have a large polar head → amphipathic → form bilayers.
Cholesterol characteristics
Rigid, non-polar ring structure
Weakly amphipathic (1 OH)
~30–35% of mammalian plasma membranes
Regulates membrane fluidity and rigidity
Cannot form membranes alone
OH associates with polar head groups.
Amphipathic lipids in water
Fatty acids → micelles
Membrane lipids → bilayers → liposomes
What determines bilayer properties?
Lipid composition:
Acyl chain length (typically 16–20 C)
Degree of unsaturation
Polar head group identity
Presence of cholesterol
Bilayers are fluid yet stable. Thickness: 4–6 nm.
Membrane melting (transition) temperature
Temperature at which membrane changes from ordered/gel to fluid state. Depends on chain length and unsaturation. Homogeneous bilayers have sharp transitions; natural membranes do NOT (mixed lipids/proteins).
Molecular dynamics of a fluid membrane
Acyl chains move freely; head groups interact with water; membrane is dynamic but cohesive. (Illustrated on page 14.)
How organisms maintain membrane fluidity in cold temperatures
Increase unsaturated fatty acids and shorter fatty acids.
In heat, increase saturated and longer fatty acids.
How cholesterol affects membrane rigidity
High T: decreases motion → increases rigidity
Low T: prevents close packing → increases fluidity
Cholesterol broadens the temperature range over which the membrane remains functional.
Types of lipid movement
Lateral diffusion: rapid & common
Transverse diffusion (flip-flop): extremely slow without enzymes
Flippases / floppases / scramblases: catalyze flip-flop; maintain leaflet asymmetry.
What defines an integral membrane protein?
Must have hydrophobic amino acids contacting acyl chains. Polar residues cluster near head groups; charged residues flank membrane. (Image on page 18.)
What secondary structures cross membranes?
α-helices and β-barrels.
MCQ alert: Transmembrane α-helices are typically hydrophobic → TRUE
Fluid mosaic model
Proteins & lipids move laterally
Restricted by cytoskeleton
Carbohydrates attach to extracellular surface
Dynamic, non-covalent assembly.
Which molecules cross membranes by simple diffusion?
Small, non-polar molecules. No protein required. Rate depends on size, gradient, and lipid solubility.
Passive vs active transport
Passive: ΔG < 0, spontaneous, down gradient
Active: ΔG > 0, requires energy
Transport proteins lower activation energy for solute movement.
ΔG for transport
ΔG = RT ln([X]destination / [X]source)
If ΔG < 0 → passive; ΔG > 0 → requires energy. Overall ΔG must be negative.
Porins (passive transporters) (5)
Found in bacteria, mitochondria
β-barrel structure, large pore
Often trimers, each with a pore
Non-selective up to ~1.5 kDa
Ion channels: highly selective based on pore size & side chain chemistry (K⁺ example on page 23)
Transporter (carrier) proteins (5)
No pores
Undergo conformational changes
Highly specific
Can be passive or active
Alternates between outward-facing & inward-facing states.
Types of carrier transport (3)
Uniport: one solute
Symport: two solutes, same direction
Antiport: two solutes, opposite directions
Primary vs secondary active transport
Primary (1°): Uses ATP hydrolysis directly
Secondary (2°): Uses ion gradient established by primary transporter (e.g., Na⁺ gradient)
For secondary: ΔGsolute > 0 but ΔGion < 0 → net ΔG < 0.
Na⁺/K⁺ ATPase
Primary active antiporter
Pumps 3 Na⁺ out, 2 K⁺ in
Electrogenic
ATP + H₂O → ADP + Pi + H⁺
Maintains major ion gradients used for many secondary transport processes.
Na⁺–glucose symporter
Secondary active transport
Glucose moves against gradient (ΔG > 0)
Na⁺ moves down gradient (ΔG < 0)
Net ΔG < 0 → glucose import is powered by Na⁺ gradient.
What increases membrane fluidity?
More unsaturated fatty acids
Shorter fatty acids
Cholesterol at low temperatures
What decreases membrane fluidity?
More saturated fatty acids
Longer fatty acids
Cholesterol at high temperatures
Why is transverse lipid movement rare?
Requires moving hydrophilic head through hydrophobic core → huge energy barrier. Only enzymes (flippases) can catalyze it.
Which transport processes saturate?
Carriers saturate (limited by turnover). Channels and simple diffusion do not saturate.
Porins vs channels vs carriers
Porins: Large, non-selective, β-barrels
Channels: Selective, pore-forming, fast
Carriers: Alternating-conformation, slow, saturable
What determines membrane thickness?
Acyl chain length, cholesterol content, head group size → typically 4–6 nm.
What are three biological/medical uses of liposomes (lipid vesicles)?
Delivery of lipid-soluble drugs (inside the bilayer).
Delivery of water-soluble drugs (inside the aqueous core).
Delivery of DNA in gene therapy (DNA in the core or associated with the surface).
How do the kinetics of passive transport by carrier proteins compare to porins/simple diffusion?
Carrier-mediated passive transport shows saturable, hyperbolic kinetics (like enzyme Km/Vmax).
Porins/simple diffusion give a more linear increase in rate with concentration (no saturation until very high).
Besides speeding flip-flop, why are flippases (and related enzymes) important for membranes?
They allow cells to maintain different lipid compositions in the two leaflets of the bilayer, which is crucial for membrane asymmetry and function.