Lipids and Bilayers

Question 1

Describe lipids?

Answer 1

They are not polymeric bu they do aggregate
Very varied
Largely hydrophobic, therefore insoluble in water
Soluble in organic solvent e.g. chloroform and methanol
They can be separated chromatographically and identified by mass spec

Question 2

What are the general biological functions of lipids?

Answer 2

1. Lipids form lipid bilayers that are essential components of biological membranes
2. Lipids containing hydrocarbon chains = energy stores
3. Many intra/intercellular signalling events involve lipid molecules

Question 3

What are the main types of lipids?

Answer 3

Triacylglycerols/triglycerides
Glycerophospholipids
Steroids

Question 4

Describe fatty acids?

Answer 4

Long hydrocarbon unbranched chains with a carboxylic acid at the end
Usually in between 14-20 carbons in the chain
Most common: palmitic, oleic, linoleic and stearic acids

They can be saturated - only single bonds
OR
They can be unsaturated - contains at least one double bond

Question 5

What are some features of saturated fatty acids?

Answer 5

Contains only single C-C bonds, fitting closely together in a regular pattern
Have strong interaction between long carbon chains
Have higher melting points
Usually solids at room temperature

Question 6

What are some features of unsaturated fatty acids?

Answer 6

Double bonds = kinks in the chain
Don't pack closely together
Fewer attractions between chains
Lower melting point
Liquids at room temp

Polyunsaturated Fatty acids = more than one C=C bond
Monounsaturated Fatty acid = one C=C bond

Question 7

What are the types of double bond within unsaturated fatty acids?

Answer 7

Cis and Trans

Cis - two H atoms on the same side of the double bond = rigid 30° kink
This is the most common

Trans - H atoms on opposite sides
Formed when polyunsaturated fatty acids from plants are ‘partially hydrogenated’
Consumption of trans fats causes cardiovascular disease

Question 8

Describe triacylglycerols?

Answer 8

Glycerol + 3 fatty acids (esterfied)
Fats and oils in plants/animals mainly consists of triacylglycerols
Nonpolar and water insoluble
Function as enery reserves (adipocytes - fat cells)
Fats provide six times the metabolic energy of equal weight of hydrated glycogen

Question 9

What are the types of triacylglycerols?

Answer 9

Simple - 3 fatty acids esterified to glycerol are the same
Mixed - different fatty acid chains are connected to glycerol

Most contain 2-3 different types
-ate at the end of a fatty acid becomes -oyl in fatty acid ester

Question 10

What are Glycerophospholipids?

Answer 10

Glycerol-3-phosphate
C1 and C2 are esterified with fatty acids
C3 has a phosphoryl group usually linked to another polar group (X)
X helps determine the name

= Amphiphilic
Non-polar aliphatic tails
Polar phosphoryl-X heads

Question 11

What are some glycerophospholipid names based on different X groups?

Answer 11

Water - Phosphaditic acid
Ethanolamine - Phosphatidylethanolamine
Choline - Phosphatidylcholine
Serine - Phosphatidylserine
Myo-inositol - Phosphatidylinositol

Question 12

What are some facts of the different glycerophospholipids?

Answer 12

Phosphatidylcholine - most abundant in cell membranes

Phosphatidylethanolamine - 2nd most abundant, helps proteins to be positioned in the membrane

Phosphatidylserine - presence on the outer membrane ofdying cells signalsmacrophages to digest them

Phosphatidylinositol - abundant in thebrain

Question 13

Give an example where glycerophospholipids are used to prevent a medical condition?

Answer 13

DPPC - major lipid of lung surfactant
Surfaces of alveoli covered in surfactant
Collapse of alveolar space is prevented by surfactant, as tightly packed DPPC (due to saturated, straight chains) resist compression

Premature infants have low surfactant production pre-birth = at risk for respiratory distress syndrome
Treated by exogenous surfactant to the lungs

Question 14

What are phospholipases?

Answer 14

Phospholipases hydrolyse glycerophospholipids
E.g. Phospholipase A2 removes the fatty acid at C2 leaving a lysophospholipid

Lysophospholipid = powerful detergent (disrupt cell membranes and lyse cells) e.g. bee/snake venom

Question 15

What are plasmalogens?

Answer 15

Glycerophospholipids, where C1 chain is linked by either and a or b unsaturated ether linkage is the cis configuration (rather than ester linkage)

Function isn’t well understood as the vinyl ether group is easily oxidised
They react with O2 free radicals - preventing free-radical damage to other organelles

Question 16

What are sphingolipids?

Answer 16

Major membrane components
Derivatives of amino alcohol sphingosine (= bond in trans)
General structure: sphingosine, fatty acid, PO4, amino alcohol

The N-acyl fatty acid derivatives of sphingosine are known as ceramides
Ceramides are the parent compounds of the more abundant sphingolipids

Question 17

What are some types of sphingolipids?

Answer 17

Sphingomyelins
Cerebrosides
Gangleosides

Question 18

Describe sphingomyelins?

Answer 18

Can have choline instead of amino alcohol but can have ethanolamine as well
Make up 10-20% of plasma membrane lipids
Rich in the myelin sheath

Question 19

Describe cerebrosides?

Answer 19

Lack a phosphate and are non-ionic
They are ceramides with a head consisting of a single sugar residue
e.g. galactocerebrosides and glucocerebrosides

Question 20

Describe gangliosides?

Answer 20

Ceramides with attached oligosaccharides that include at least one sialic acid residue

Primarily components of cell surface membranes and 6% of brain lipids
Receptors for pituitary glycoprotein hormones and the cholera toxin
Likely involved in cell growth and differentiation & carcinogenesis

Question 21

What is a disease of gangliosides?

Answer 21

Tach Sachs disease
A fatal neurodegenerative disorder
The inability to catabolise gangliosides

Question 22

What are steroids?

Answer 22

Eukaryotic origin - contains 4 fused rings (A-D)
A-C has 6C and D has 5C

Can be further classified as a sterol due to C3-OH group e.g. in cholesterol

Question 23

Describe cholesterol?

Answer 23

Forms 30-40% of plasma membrane lipid
Provides integrity and fluidity to the membrane - fluidity allows cells to change shape rapidly
Weak amphiphilic character due to OH group - this interaction with the head of the phospholipids also holds the membrane together
At high temperatures, they attract each other and prevent the membrane from breaking down
Fused ring provides great rigidity

Question 24

What is cholesterol the precursor of in mammals?

Answer 24

Steroid hormones
They control a variety of physiological functions through regulation of gene expression
They are classified according to the physiological responses the evoke

Question 25

What are some steroid hormones?

Answer 25

Glucocorticoids - affect carbohydrate, protein and lipid metabolism
e.g. cortisol - responses to stress, infection etc
Aldosterone - regulate the excretion of salt and water by the kidneys
Androgens & estrogens - affect sexual development and function e.g. testosterone and estradiol

Question 26

What is another sterol derivative?

Answer 26

Vitamin D
This regulates Ca2+ metabolism

Deficiency leads to rickets - stunted growth and deformed bones

Question 27

What are some common lipids that aren’t membrane components?

Answer 27

Isoprenoids - 5C units, soluble in the lipid bilayer e.g. ubiquinone
Vitamin A (Retinol) - triggers signalling through the optic nerve and stimulates tissue repair
Vitmain K - participates in carboxylation of Glu resididues in proteins involved in blood clotting
Vitmain E - an antioxidant that prevents oxidative damage to membrane proteins and lipids

Question 28

What are some uncommon lipids that aren’t membrane components?

Answer 28

Eicosanoids - derived from arachidonic acid
20C compounds
The don’t move through the bloodstream but act locally (decompose within secs to mins)

The eicosanoids act at very low concentrations and are involved in the production of pain and fever, and in the regulation of blood pressure, blood coagulation, and reproduction

Question 29

Why do lipids aggregate?

Answer 29

The hydrophobic effect: minimises unfavourable contacts between water and hydrophobic tails but permit the solvation of the polar heads
Due to amphipathic character

Question 30

What does the outcome of the aggregation depend on? Forming what?

Answer 30

Length of fatty acid chain
Temperature
Degree of saturation (C=C or C-C)

Micelle, bilayer or liposome

Question 31

Describe micelles?

Answer 31

Single tailed amphipiles - form spheroidal or ellipsoidal (oval) micelles
The single tail = tapered shape (hydrated head is wider than the tail) forming a cone shaped van der Waal envelope
They can develop water filled spaces

Head on the outside with the water and the tails on the inside

Question 32

Describe lipid bilayers?

Answer 32

Two hydrocarbon tails on the lipid forms a lipid bilayer
Heads above and below, with tails facing in practically touching
60 Å thick

Sheets of phospholipid bilayers seal their edges - forming a spherical bilayer enclosing an aqueous central compartment

Question 33

Describe a liposome?

Answer 33

Doughnut shape - heads forming a circle on the very outside and very inside with the tails pointing towards each other

Question 34

What property do lipid bilayers have?

Answer 34

Fluid-like properties - the membranes are 2D fluids

Lateral diffusion - movement of lipids within its own plane of the bilayer (rapid)

Transverse diffusion (flip-flop) - transfer of a lipid molecule across a bilayer (slow and rare)

Question 35

Why doesn’t transverse diffusion happen often?

Answer 35

The hydrated polar head has to pass through the anhydrous hydrocarbon core of the bilayer to the other side

Requires flippases to catalyse the movement from one layer of the bilayer to the other

Question 36

What is significant about the interior of the lipid bilayer?

Answer 36

It is in constant motion due to rotations around the C=C bonds in the tails = low viscosity

Question 37

What is the fluidity of a bilayer dependent on?

Answer 37

Temperature
Above the transition state: Highly mobile (liquid crystal)

Below the transition state: gel like solid (loses fluidity)

The transition state temperature of the bilayer increases with the chain length and the degree of saturation
Cholesterol decreases fluidity due to rigidity