#13 Lipids and Membranes

Membrane function

boundary between cytosol/extracellular environment, intracellular compartmentalization for distinct content/properties

Membrane structure

thin film of lipids/protein molecules, held together by non-covalent interactions, self-sealing, non-elastic but flexible/deformable

Lipids

hydrophobic or amphipathic organic molecules insoluble in water, soluble in organic solvents

Fatty acids

carboxylic acid with aliphatic chain, either saturated or unsaturated, used to derive lipid-based molecules in the cell, can diffuse freely into cell (uptake facilitated by proteins)

aliphatic

non-aromatic carbon compounds (alkanes, alkenes, alkynes)

Triacylglycerides (storage lipid)

glycerol molecule esterified (oxygen bridge) to 3 fatty acids, released by lipases (via hydrolysis), primary energy storage form in cells, "fat" stored in adipose cells

waxes (storage lipids)

long-chain fatty acid linked via ester oxygen to long-chain alcohol, completely water-insoluble

Phospholipids (membrane lipid)

key component of cell membranes, form lipid bilayers with polar head and non-polar tails, properties affected by head group (size, charge, etc.) and number/size of lipid tails (saturated vs unsaturated)

Glycerophospholipids (phospholipids)

use glycerol to connect FA tails and head groups

Glycerol

propane-1,2,3-triol

Phosphatidylcholine (PE)

neutral head group, N+-3(CH3)

phosphatidylserine (PS)

negative head group (-COO- NH3+)

Phosphatidylethanolamine (PE)

neutral head gorup (NH3+)

sphingolipids (phospholipids)

use sphingosine (amino alcohol) to connect FA tails and head groups

sphingosine

18C amino alcohol, unsaturated chain

sphingomyelin (SM)

neutral net charge, used in myelin sheets due to strong H-bonds and tight packing

glycolipids

lipids with carbohydrate attached, used for membrane stability + cellular recognition

sterols

compounds structurally similar to cholesterol

cholesterol

affects membrane stability/fluidity, rings connect a polar head group with hydrocarbon tail, able to fit in between kinks of phospholipids in membrane

Droplet

non-amphipathic (polar + non-polar regions) lipids bunch together

Bilayers

cylindrical lipids, polar head groups facing out, lipid tails in

Micelles

conical lipids with larger heads and smaller tails form spheres with their polar heads and non-polar tails inside

Cubic phases

where inverted conical lipids have their large non-polar tails facing out, does not occur in cells

Unsaturated hydrocarbons

more fluid due to more space to move freely, more permeable (larger gaps), thinner (tails can overlap)

Saturated hydrocarbons

very tight, less fluid, less permeable, thicker (tails cannot overlap)

Cholesterol

impacts fluidity with temperature-dependant manner, low temp – increases fluidity due to breaking up tight packing, high-temp – decreases fluidity due to rigid ring structure

Lipid distribution

fits membrane function (different comparments/leaflets)

Asymmetric leaflet distribution

allows for different signaling, distinct membrane associated processes, ID of apoptotic cells

Extracellular side - choline head groups (PC, SM), glycolipids)

cytosol side - terminal amino head groups (PE, PS), negative phospholipids (PS, PI)

Domains

lateral phase separation in artificial bilayers, breaks homogeneity of bilayer with domains with different properties

Lipid rafts

large scale lipid phase segregation, existence debated

Raft domain

temporal enrichment with specific membrane proteins/lipids concentrating

Phosphoinositides (PIPs)

phosphorylated phosphatidylinositol (PI) molecules, specific kinase for each OH-position, mediate timing/signaling/trafficking

Lipid biosynthesis - ER

enzymes in ER produce majority of cellular lipids/membrane building blocks (PC, PE, PtdIns, sphingolipids, cholesterol, TAGs)

triacylglycerols (TAGs)

stored in lipid droplet bud from ER

Lipid biosynthesis - Mitochondria

PS decarboxylase (converts PS to PE) found here, has more PE, little PS, also has de novo synthesis of cardiolipin in inner mitochondrial membrane

PS decarboxylase

converts PS to PE in mitochondria

lipid trafficking

can occur via equilibrative (along energy gradient) or active (energy consuming mechanisms)

a) phospholipid transfer protein

b) sterol transfer protein

c) sphingolipid transfer protein

membrane proteins

can occur via equilibrative (along energy gradient) or active (energy consuming mechanisms)

transmembrane proteins

proteins that span one or both leaflets of the membrane, mostly in a-helix conformation

Integral membrane proteins

proteins that have protein domains in the membrane leaflets

Beta-barrel

made of beta sheets with hydrophobic aas facing out, allows for trafficking of proteins

Lipid-anchored membrane proteins

proteins with fatty acid/isoprenyl/GPI anchor (non-protein)

membrane dynamics

Membrane fission/fusion: necessary to create/remodel membranes, energy dependent due to energy necessary to join membranes