Lecture 4 Lipid Membranes

Question 1

Phospholipid structure

Answer 1

Polar phosphate hydrophilic head
Glycerol hydrophobic tails

Phosphatidylcholine is a typical and most common phosphoglyceride

Membranes assembled through non-cov association of ampiphatic phospholipid building blocks

Phosphoglycerides : phospholipids with 3 carbon glycerol backbone.
Hydrophobic tail formed by esterification of 2 of its OH groups to fatty acids
Hydrophilic head - it’s 3rd OH group bound to a phosphate group which may be linked to another hydrophobic head (choline)

C-C bond rotation in backbone puts head and tails on opposite ends of the molecule making it ampiphatic

Question 2

pH and charge

Answer 2

At neutral pH some phosphoglycerides have no charge e.g. phosphatidylcholine and phosphatidylethanolamine

Others e.g. phosphatidylinositol and phosphatidylserine have a single net neg charge

Question 3

Phosphoinositides

Answer 3

In inositol head group hydroxyl groups may be further modified with phosphates to yield a class of lipids called phosphoinositides which have a function in signal transduction

Question 4

Fatty acids in phospholipids

Answer 4

Fatty acids in phospholipid hydrophobic tails (fatty acyl groups) vary in length and number of carbon double bonds (unsaturated). Double bonds define shape of the lipid

Question 5

Carbon bonds and double bonds

Answer 5

Carbon double bonds are not rotatable like carbon single bonds.

Most natural double carbon bonds are Cis. They introduce a rigid kink in the otherwise flexible acyl chain of asat fatty acid. This prevents tight packing in lipid bilayer membrane.

Artificial desaturation processes make trans bonds in molecules known as trans fats

Question 6

Effect of double bond on shape of fatty acids

Answer 6

Cis C=C creates rigid kink in hydrocarbon tail

Trans C=C would be much more linear and more similar in structure to saturated fatty acid chain

Question 7

Biomembranes contain 3 main classes of ampiphatic lipids

Answer 7

Phospholipid - generic term for any ampiphatic lipid with a phosphate based head group and a two chain hydrophobic tail

Biomembranes have 3 classes of ampiphatic lipids:

Phosphoglycerides
Sphingolipids
Sterols

They differ in chemical structure abundance and function in membrane

All phosphoglycerides are phospholipids, some sphingolipids are and no sterols are.

Question 8

Sphingolipids : sphingosine and C2

Answer 8

3 carbon backbone analogous to 3carbon glycerol. At C3 there’s a long chain amino alcohol called a sphingosine.

All sphingolipids derived from sphingosine.

At C2 there’s a fatty acid, usually sat or monosat and can be 16/18/22 or 24 carbons long

Question 9

Sphingolipids: ceramide and sphingomyelin

Answer 9

Ceramide is parent compound other polar heads can be attached at CH2-O

Sphingomyelin is the most abundant sphingolipid (10-25% of plasma membrane) a phospholipid formed of phosphocoline attached to terminal hydroxyl group of sphingosine. Structure similar to phosphatidylcholine

Question 10

Sphingolipids: glycosphingolipids

Answer 10

Sub group of sphingolipids that contain saccharide headgroups that constitute 2-10% of total plasma membrane lipid. Most abundant in nerve tissue

Question 11

Cholesterol and related lipids - sterols

Answer 11

Cholesterol and it’s analogues constitute the 3rd important class of membrane lipids - the sterols.

Basic sterol structure is a 4 ring isopropenoid based hydrocarbon. No phosphate so they are not phospholipids.

Principal yeast sterol is ergosterol in plants it’s stigmasterol these differ slightly from cholesterol the main animal sterol.

Sterols are the base for most antifungal drugs

Question 12

Cholesterol

Answer 12

Like other sterols has a hydroxyl substitute on one ring. Almost entirely hydrocarbon. Ampiphatic because hydroxyl group can interact with water.

Most abundant in plasma membranes of mammalian cells (>35% in some cell types.)

Between 59-90% cholesterol is present in plasma membranes and associated vesicles

Question 13

Cholesterol function in bilayer

Answer 13

Sterols are too hydrophobic to form bilayer alone must intercalate between phospholipids to be incorporated.

Sterols provide structural support and prevent too close packing of phospholipid acyl- chains to maintain membrane fluidity with rigidity for mechanical support

Question 14

Lipid composition diff in exoplasmic and cytosolic leaflets

Answer 14

Non symmetrical bilayer

Almost all sphingomyelin and phosphatidylcholine found in exoplasmic leaflet

Phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol usually in cytosolic leaflets

So cytosolic leaflets more neg. charged

• and phosphatidylinositol in good location for signalling

Question 15

Effect of lipid composition on bilayer thickness/curvature

Answer 15

Pure sphingomyelin (SM) bilayer is thicker than one formed of a phosphoglyceride such as phosphatidylcholine (PC.)

Cholesterol has a lipid ordering effect on phosphoglyceride bilayers increasing their thickness, but it doesn’t effect the thickness of a more ordered SM bilayer

Phospholipids such as PC have a cylindrical shape and form flat monolayers whereas those with smaller head groups e.g phosphatidylethanolamine (PE) have a conical shape.

Bilayer enriched with PC in exoplasmic leaflet with PE on cytosolic leaflet causes a natural curve

Question 16

Membrane dynamics: lipid structure

Answer 16

Higher Tm in sphingomyelin and other sphingolipids. This introduces lateral heterogeneity into plasma membranes:

Lipid rafts - gel phase in a fluid phase ‘sea’

Question 17

Lipid rafts

Answer 17

Membrane microdomains enriched in sphingolipids, cholesterol and certain (e.g. lipid-linked) proteins.

Thicker and less fluid than neighbouring domains